In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

OBJECTIVE: To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: From September 2021 to September 2023, we enrolled LDH patients (LDH group, n=31) and age- and sex-matched healthy controls (HCs, n=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session, totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally, participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score, whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales. RESULTS: Following SMT treatment, pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1, TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise P<0.005; clusters >30; FDR correction). Additionally, the most substantial enhancement in ReHo values was observed for the Cuneus_R, while the most prominent reduction was noted for the Olfactory_R (voxelwise P<0.005; clusters >30; FDR correction). Moreover, a comparative analysis revealed that, in contrast to HCs, LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise P<0.005; clusters >30; FDR correction). Furthermore, the most significant enhancement in ReHo values was observed for Postcentral_L, while the most prominent reduction was identified for ParaHippocampal_L (voxelwise P<0.005; clusters >30; FDR correction). Notably, correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (r=0.9333, P<0.0001). CONCLUSIONS Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network, represented by the Cuneus_R, is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT06277739).
Humans ; Magnetic Resonance Imaging ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Brain/diagnostic imaging* ; Adult ; Manipulation, Spinal/methods* ; Middle Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management ; Rest ; Case-Control Studies

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Post-stroke depression(PSD)is one of the commonly-seen complications after stroke,which seriously affects patients'quality of life and outcome of disease.Traditional Chinese medicine(TCM)classifies PSD as the co-morbidity of stroke and depression.This paper explored the pathogenesis and therapeutic principles of PSD from the view of"heart-blood-vessels"integration.It is proposed that PSD originates from the lesions of blood and vessels,and then the heart-body is involved;the lesions of heart,blood and vessels can cause the disorders of spirit.The core pathogenesis is due to the deficiency of heart qi,unsmoothed circulation of the vessels,and blood stasis causing depression of spirit.The principle of intervention of PSD should be focused on protecting vessels and regulating blood,nourishing heart and tranquilizing.Protecting vessels can be achieved by generating vessels,soothing vessels,and unblocking vessels through the application of Shengmai San,Zhi Gancao Decoction,and Tongmai Sini Decoction respectively.Regulating blood can be achieved by activating blood and generating blood.For activating blood,Danshen Decoction and Xuefu Zhuyu Decoction can be employed;for generating blood,Bazhen Decoction,Renshen Yangrong Decoction and Danggui Buxue Decoction can be employed.For nourishing heart and tranquilizing,the modified Gan Mai Dazao Decoction and Guipi Decoction can be employed.The view of"heart-blood-vessels"integration makes up for the disadvantages in separating the physique from the spirit,and in separating the structure from the function in the theory of the vessels and collaterals,and expands the approach of TCM treatment for PSD.

Abdominal war trauma is a common and high-risk type of injury in the modern battlefield,with rapid changes in condition and a high mortality rate.There is an urgent need for emerging medical technologies to improve the efficiency and success rate of first aid for military casualties.With the development of artificial intelligence(AI),5G,and other emerging technologies,the concept of intelligent medical treatment is gradually forming and can assist in the diagnosis and treatment of abdominal trauma.This paper reviews the characteristics of abdominal war trauma in modern wars,discusses the application of intelligent medical treatment for abdominal war trauma and its drawbacks to be solved,aiming to provide reference for research related to abdominal war trauma.

Objective To evaluate the efficacy and safety of preoperative bladder artery embolization followed by transurethral resection of bladder tumor(TURBt)in treating bladder cancer.Methods A retrospective analysis was conducted on the clinical data of 129 bladder cancer patients treated at the Fourth Affiliated Hospital of Soochow University from January 2021 to June 2024.Exclusions included 2 cases of acute bleeding with shock,3 cases requiring staged surgery due to poor intraoperative visualization,7 cases with other malignancies,12 cases without TURBt performed within 24 hours after embolization,and 1 case where selective bladder artery embolization failed.Patients were divided into two groups based on whether they underwent pre-TURBt embolization.Group A(n=61)underwent TURBt alone,while Group B(n=43)underwent TURBt within 24 hours after bladder artery embolization.There were no statistically significant differences in gender composition,tumor size,or other clinical characteristics between the two groups(P＞0.05).Statistical comparisons were made between the two groups regarding operation time,intraoperative blood loss,postoperative hospital stay,duration of postoperative catheterization,and incidence of adverse reactions.Results In Group A,the mean operation time was(67.9±14.2)min,intraoperative blood loss was(80.7±24.7)mL,postoperative hospital stay was(8.5±1.6)days,and catheterization duration was(6.9±1.1)days.In Group B,the mean operation time was(54.0±12.6)min,intraoperative blood loss was(58.6±27.3)mL,postoperative hospital stay was(7.3±1.4)days,and catheterization duration was(6.4±0.9)days.Operation time,intraoperative blood loss,postoperative hospital stay,and catheterization duration were significantly lower in Group B compared to Group A(P＜0.05).There was no statistically significant difference in the incidence of postoperative adverse reactions between the two groups(P＞0.05).Conclusion Preoperative bladder artery embolization followed by TURBt for bladder cancer reduces tumor blood supply,thereby decreasing intraoperative bleeding.This approach effectively minimizes surgical bleeding,shortens operation time and postoperative hospital stay,with minimal side effects.It represents a safe and effective combined treatment method worthy of clinical promotion and application.

BACKGROUND: Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths. METHODS: This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate. RESULTS: From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management. CONCLUSIONS The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.
Humans ; China/epidemiology* ; Stroke/mortality* ; Rural Population/statistics & numerical data* ; Male ; Female ; Urban Population/statistics & numerical data* ; Middle Aged ; Aged ; Aged, 80 and over ; Adult

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

In this study, Saccharomyces cerevisiae R0 was used as the chassis cell to synthesize oleanolic acid from scratch through the heterologous expression of β-amyrin synthase(β-AS) from Glycyrrhiza uralensis, cytochrome P450 enzyme CYP716A154 from Catharanthus roseus, and cytochrome P450 reductase AtCPR from Arabidopsis thaliana. The engineered strain R1 achieved shake flask titres of 5.19 mg·L~(-1). By overexpressing enzymes in the pentose phosphate pathway(PPP)(ZWF1, GND1, TKL1, and TAL), the NADH kinase gene in the mitochondrial matrix(POS5), truncated 3-hydroxy-3-methylglutaryl-CoA reductase(tPgHMGR1) from Panax ginseng, and farnesyl diphosphate synthase gene(SmFPS) from Salvia miltiorrhiza, the precursor supply and intracellular reduced nicotinamide adenine dinucleotide phosphate(NADPH) supply were enhanced, resulting in an 11.4-fold increase in squalene yield and a 3.6-fold increase in oleanolic acid yield. Subsequently, increasing the copy number of the heterologous genes tPgHMGR1, β-AS, CYP716A154, and AtCPR promoted the metabolic flow towards the final product, oleanolic acid, and increased the yield by three times. Shake flask fermentation data showed that, by increasing the copy number, precursor supply, and intracellular NADPH supply, the final engineered strain R3 could achieve an oleanolic acid yield of 53.96 mg·L~(-1), which was 10 times higher than that of the control strain R1. This study not only laid the foundation for the green biosynthesis of oleanolic acid but also provided a reference for metabolic engineering research on other pentacyclic triterpenoids in S. cerevisiae.
Oleanolic Acid/biosynthesis* ; Saccharomyces cerevisiae/metabolism* ; Industrial Microbiology ; Microorganisms, Genetically-Modified/metabolism* ; Plants/enzymology* ; Fermentation ; Metabolic Engineering

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans