This study employed 16S r RNA gene high-throughput sequencing and metabolomics to explore the mechanism of Angelicae Dahuricae Radix polysaccharides(RP) in the treatment of ulcerative colitis(UC). A mouse model of UC was induced with 2. 5% dextran sulfate sodium. The therapeutic effects of RP on UC in mice were evaluated based on changes in body weight, disease activity index( DAI), and colon length, as well as pathological changes. RT-qPCR was performed to assess the m RNA levels of interleukin(IL)-6, IL-1β, tumor necrosis factor(TNF)-α, myeloperoxidase(MPO), mucin 2(Muc2), Occludin, Claudin2, and ZO-1 in the mouse colon tissue. ELISA was employed to measure the expression of IL-1β and TNF-α in the colon tissue. The intestinal permeability of mice was evaluated by the fluorescent dye permeability assay. Immunohistochemistry was employed to detect the expression of Muc2 and occludin in the colon tissue. Changes in gut microbiota and metabolites were analyzed by 16S r RNA sequencing and ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry( UPLC-Q-Exactive Plus Orbitrap MS), respectively. The results indicated that low-dose RP alleviated general symptoms, reduced colonic inflammation and intestinal permeability, and promoted Muc2 secretion and tight junction protein expression in UC mice. In addition, low-dose RP increased gut microbiota diversity in UC mice and decreased the relative abundance of harmful bacteria such as Ochrobactrum and Streptococcus. Twenty-seven differential metabolites were identified in feces, and low-dose RP restored the levels of disturbed metabolites. Notably, arginine and proline metabolism were the most significantly altered amino acid metabolic pathways following lowdose RP intervention. In conclusion, RP can ameliorate general symptoms, inhibit colonic inflammation, and maintain intestinal mucosal barrier integrity in UC mice by modulating gut microbiota composition and arginine and proline metabolism.
Animals ; Gastrointestinal Microbiome/drug effects* ; Colitis, Ulcerative/genetics* ; Mice ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Polysaccharides/administration & dosage* ; Angelica/chemistry* ; Humans ; Colon/metabolism* ; Disease Models, Animal ; Mucin-2/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

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*

Objective To design a combat rescue specialized physical training simulator to solve the problems of the existing combat rescue physical traing in multifunctionality and simulation vividness.Methods The simulator was divided into three types for stretcher handling,land combat rescue and marine rescue based on the application scenerio and functional positioning,and into three grades of basic level,intensive level and ultra intensive level based on the loaded mass and additional weight object.The main components of the simulator included a manikin,a bionic joint and addtional weight objects.The manikin was made up of outer skin,inner liner and skeleton;the bionic joint was made of stainless steel with surface electrophoresis treatment,and was composed of high-strength medal bearing shafts with multiple disc springs and damping mechanisms;the additional weight objects involued in high-intensity cast iron or lead blocks,which were pre-embedded,mounted or srtapped into the simulator.The simulator was verified with body shape and mass detection,drop test,waterproof test and drag test.Results It's proved the simulator gained advantages in vividness for body shape and mass,bionic joint structure and adaptability to training environments and could be used for graded physical training in typical combat rescue scenerios.Conclusion The simulator developed solves the problems of the combat rescue specialized physical training equipment,and facilitates the enhancement of physical training of combat rescue personnel.[Chinese Medical Equipment Journal,2025,46(1):33-37]

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Objective To explore the protective effects of genetically modified porcine erythrocyte suspension as a subnormothermic normoxic mechanical perfusate on hypoxic-ischemic brain injury in cynomolgus monkeys caused by traumatic hemorrhage.Methods Cynomolgus monkeys were randomly divided into positive and negative control groups(a total of 3 monkeys,with 3 left cerebral hemispheres as the positive control group and 3 right cerebral hemispheres as the negative control group)and the subnormothermic perfusion group(n=3).The positive control group was directly sampled 1 hour after circulatory arrest,while the negative control group was placed at subnormothermic conditions for 6 hours after circulatory arrest.The subnormothermic perfusion group underwent 6 hours of subnormothermic normoxic mechanical perfusion of the bilateral common carotid arteries of the cynomolgus monkey hypoxic-ischemic brain injury model using genetically modified porcine erythrocyte suspension 1 hour after circulatory arrest.Before perfusion,cross-matching experiments were conducted between the six genetically modified pig and the cynomolgus monkeys.After the start of perfusion,the levels of routine blood indicators in the perfusate were detected at 0,1,2,3,4,5 and 6 hours.Blood oxygen saturation was recorded,and the levels of Na+,K+,Ca2+,glucose and blood pH in the perfusate were measured,as well as the levels of IgG and IgM in the perfusate.After 6 hours of perfusion,the water content of the brain tissue was measured.Nissl staining was performed on the frontal cortex and hippocampal regions,and immunofluorescence staining was used to detect the expression of glial fibrillary acidic protein(GFAP),ionized calcium-binding adapter molecule 1(Iba1)and neuronal nuclear antigen(NEUN).Results The cross-matching results between the six genetically modified pig and the cynomolgus monkeys were negative.The number of red blood cells in the perfusate decreased significantly at 3 hours of perfusion,and the hemoglobin level showed a downward trend at 1,3,5 and 6 hours.The number of white blood cells and platelets decreased at all time points.The blood oxygen saturation in the subnormothermic perfusion group remained stable at 95%-98%,and the levels of blood oxygen saturation,Na+,Ca2+,glucose and pH were stable,while the K+level first increased and then decreased.There was no significant difference in the levels of IgG and IgM before and after perfusion.The water content of brain tissue at the end of perfusion in the subnormothermic perfusion group was significantly higher than that in the positive control group(P<0.001).Nissl staining results showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex of the subnormothermic perfusion group maintained better morphological integrity,with no significant increase in enlarged and deformed cells.In the hippocampal CA1 region,there was a slight increase in enlarged and deformed cells,and a few cells with undamaged structures showed reduced cell size.In the hippocampal dentate gyrus,fewer granule neurons had compromised structural integrity,with increased cell edema.NEUN immunofluorescence staining showed that compared with the positive control group,the pyramidal neurons in the prefrontal cortex and hippocampal CA1 region of the subnormothermic perfusion group had better morphological states,with clear axons.The granule cells in the hippocampal dentate gyrus were well preserved,but the nuclei were less well protected.GFAP immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had sparser protrusions that were more tightly associated with neurons.Iba1 immunofluorescence staining showed that compared with the positive control group,the subnormothermic perfusion group had thicker and fewer protrusions.Conclusions Compared with the positive control group,subnormothermic normoxic mechanical perfusion with genetically modified porcine erythrocyte perfusate increases brain tissue edema in cynomolgus monkeys,but better preserves the morphological integrity of neurons and glial cells.The protective effects may be related to the continuous oxygen and energy supply,maintenance of ion homeostasis and perfusate pH,reduced rejection,and low metabolic state of the whole brain.

Aim To design and synthesize a series of glycyrrhetinic acid derivatives by using glycyrrhetinic acid as the parent nucleus,screen their antitumor activ-ities,and investigate the in vitro and in vivo antitumor effects and mechanisms of the most active compound.Methods MTT assay was used to screen for the com-pound with the most potent antitumor activity.MTT as-say,wound healing assay,colony formation assay and Transwell migration assay were used to evaluate the effects of the compound on tumor cell viability and mi-gration.Flow cytometry was employed to assess the im-pact of the compound on tumor cell cycle progression and apoptosis.Western blot was conducted to verify the effects on the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3.A mouse model of hepatocellular carcinoma ascites tumor was estab-lished to examine the antitumor effects of the compound in vivo.Results Compound C22 was identified as having the most significant inhibitory effect on hepato-cellular carcinoma cells.C22 inhibited the viability and migration of hepatocellular carcinoma cells in a time and concentration-dependent manner.C22 upreg-ulated the expression of pro-apoptotic proteins Bax,caspase-3 and cleaved caspase-3 in hepatocellular car-cinoma cells,induced apoptosis,and arrested the cell cycle in the G0/G1 and S phases.C22 significantly re-duced the growth of mouse hepatocellular carcinoma as-cites tumors and prolonged survival.Conclusion Glycyrrhetinic acid derivative C22 significantly inhibits the viability and migration of hepatocellular carcinoma cells in vitro and in vivo,and induces cell cycle arrest and apoptosis.

AIM To investigate the effects of Wenyang Jiedu Tongluo Recipe(WYJDTLR)on macrophage recruitment and polarization function in a mouse model of diabetic kidney disease(DKD).METHODS 50 db/db mice were randomly divided into the model group,the valsartan group(10.29 mg/kg)and the high-dose,medium-dose and low-dose WYJDTLR groups(26.52,13.26 and 6.63 g/kg),with 10 mice in each group,in contrast to another 10 db/m mice of the blank group.After 8 weeks of administration,the mice had their levels of fasting blood glucose,24-hour urinary protein quantity(24h-UTP),serum creatinine(Scr)and blood urea nitrogen(BUN)observed;their morphological changes of renal tissues observed by HE staining;their degree of renal glycogen deposition observed by PAS staining;their degree of renal fibrosis observed by Masson staining;their levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1 β in renal tissue detected by ELISA;their renal protein expressions of VCAM-1 and ICAM-1 detected by IHC and Western blot;and their renal expressions of CD86 and CD206 detected by IF.RESULTS Compared with the model group,the WYJDTLR groups displayed decreased levels of fasting blood glucose,24h-UTP,Scr and BUN(P＜0.05,P＜0.01);improved degree of glomerular hypertrophy,mild proliferation of mesangial cells,dilatation of renal tubular,vacuolar degeneration of renal tubular epithelial cells,deposition of glomerular glycogen,and fibrosis of renal tissues(P＜0.01);decreased levels of MCP-1 and MCF-1 in serum and TNF-α and IL-1β in renal tissue(P＜0.05,P＜0.01);decreased renal protein expressions of VCAM-1 and ICAM-1(P＜0.05,P＜0.01),thus reduced the recruitment of macrophages to the kidney;decreased renal CD86 protein expression(P＜0.01);and increased CD206 protein expression(P＜0.01),thus inhibited M1-type polarization of macrophages and promoted M2-type polarization of macrophages.CONCLUSION WYJDTLR can delay the DKD progression in mice by reducing the occurrence of inflammatory reactions through reducing the level of macrophage recruitment factor,inhibiting the M1-type polarization,and promoting the M2-type polarization.

OBJECTIVE: To screen the population for acupuncture treatment of neck pain, using functional magnetic resonance imaging (fMRI) technology and based on machine learning algorithms. METHODS: Eighty patients with neck pain were recruited. Using FPX25 handheld pressure algometer, the tender points were detected in the areas with high-frequent onset of neck pain and high degree of acupoint sensitization. Acupuncture was delivered at 4 tender points with the lowest pain threshold, once every two days; and the treatment was given 3 times a week and for 2 consecutive weeks. The amplitude of low-frequency fluctuation (ALFF) of the brain before treatment was taken as a predictive feature to construct support vector machine (SVM), logistic regression (LR), and K-nearest neighbors (KNN) models to predict the responses of neck pain patients to acupuncture treatment. A longitudinal analysis of the ALFF features was performed before and after treatment to reveal the potential biological markers of the reactivity to the acupuncture therapy. RESULTS: The SVM model could successfully distinguish high responders (48 cases) and low responders (32 cases) to acupuncture treatment, and its accuracy rate reached 82.5%. Based on the SVM model, the ALFF values of 4 brain regions were identified as the consistent predictive features, including the right middle temporal gyrus, the right superior occipital gyrus, and the bilateral posterior cingulate gyrus. In the patients with high acupuncture response, the ALFF value in the left posterior cingulate gyrus decreased after treatment (P<0.05), whereas in the patients with low acupuncture response, the ALFF value in the right superior occipital gyrus increased after treatment (P<0.01). The longitudinal functional connectivity (FC) analysis found that compared with those before treatment, the high responders showed the enhanced FC after treatment between the left posterior cingulate gyrus and various regions, including the bilateral Crus1 of the cerebellum, the right insula, the bilateral angular gyrus, the left medial superior frontal gyrus, and the left middle cingulate gyrus (GRF: corrected, voxel level: P<0.05, mass level: P<0.05). In contrast, the low responders exhibited the enhanced FC between the left posterior cingulate gyrus and the left Crus2 of the cerebellum, the left middle temporal gyrus, the right posterior cingulate gyrus, and the left angular gyrus; besides, FC was reduced in low responders between the left posterior cingulate gyrus and the right supramarginal gyrus (GRF: corrected, voxel level: P<0.05, mass level: P<0.05). CONCLUSION This study validates the practicality of pre-treatment ALFF feature prediction for acupuncture efficacy on neck pain. The therapeutic effect of acupuncture on neck pain is potentially associated with its impact on the default mode network, and then, alter the pain perception and emotional regulation.
Humans ; Neck Pain/physiopathology* ; Acupuncture Therapy ; Female ; Male ; Adult ; Middle Aged ; Machine Learning ; Magnetic Resonance Imaging ; Young Adult ; Brain/physiopathology* ; Acupuncture Points ; Aged