OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

This article summarizesd Professor Li Zhigang's experience in treating limb dysfunction after acute disseminated encephalomyelitis(ADEM)by acupuncture.Prof.Li respected the classical theory of Chinese medicine,which is to seek the root cause of the disease,clarified the disease mechanism of"deficiency of Yangming leads to longitudinal tendons and unfavorable belt veins",and followed the principle of"treating flaccidity syndrome only by taking advantage of Yangming",and combined with the morbidity characteristics of ADEM that occurs in children,emphasized the important influence of regulating the root of innate and acquired in the treatment of the disease.The importance of regulating the essence of congenital and acquired constitution in the treatment of this disease was emphasized,taking into account the importance of regulating the mind and spirit.The main acupoints of Yangming Stomach Meridian,Large Intestine Meridian,Spleen Meridian,and Governor Vessel,together with the five main points of the lower limbs and the main points of water-inducing,all together play the role of tonifying the middle energizer,benefiting the essence and filling in the marrow,and strengthening the muscles and bones.

This article summarizesd Professor Li Zhigang's experience in treating limb dysfunction after acute disseminated encephalomyelitis(ADEM)by acupuncture.Prof.Li respected the classical theory of Chinese medicine,which is to seek the root cause of the disease,clarified the disease mechanism of"deficiency of Yangming leads to longitudinal tendons and unfavorable belt veins",and followed the principle of"treating flaccidity syndrome only by taking advantage of Yangming",and combined with the morbidity characteristics of ADEM that occurs in children,emphasized the important influence of regulating the root of innate and acquired in the treatment of the disease.The importance of regulating the essence of congenital and acquired constitution in the treatment of this disease was emphasized,taking into account the importance of regulating the mind and spirit.The main acupoints of Yangming Stomach Meridian,Large Intestine Meridian,Spleen Meridian,and Governor Vessel,together with the five main points of the lower limbs and the main points of water-inducing,all together play the role of tonifying the middle energizer,benefiting the essence and filling in the marrow,and strengthening the muscles and bones.

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4⁺ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.