Nine compounds were isolated and purified from 90% ethanol extract of Alstonia mairei Lévl by using various chromatographic methods, including silica gel, SephadexLH-20, MCI Gel and ODS column chromatography, combined with semi-preparative liquid phase separation methods. Modern spectroscopic methods (1D and 2D NMR, UV, IR, MS, etc.) were used to identify the structures of the isolated compounds. They were identified as mairoside A (1), 3′,6-di-O-sinaloylsucrose (2), myristic acid (3), methyl myristate (4), ethyl myristate (5), 3,4,5-trimethoxycinnamic acid (6), 3,4,5-trimethoxybenzoic acid (7), vinoline (8), kaempferol-3-O-rutinoside (9), among which compound 1 is a new glycoside, compounds 4 and 5 are new natural products, and the nuclear magnetic data of compound 4 were reported for the first time.

The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

Resveratrol(Res) is a kind of polyphenolic compound, possessing multiple biological activities such as antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. In recent years, the cardiovascular protective mechanism of Res has become a research hotspot. Studies have shown that Res has a protective effect on the cardiovascular system through various pathways, such as inhibiting oxidative stress, regulating ferroptosis of cells, improving ischemia-reperfusion(I/R) injury, regulating lipid metabolism, suppressing inflammatory responses, and enhancing endothelial function. It can also alleviate cardiotoxicity caused by drugs and chemicals. In terms of oxidative stress, Res reduces the level of intracellular reactive oxygen species(ROS) by enhancing the expression of proteins such as silent information regulator 1(SIRT1) and regulating mitochondrial function, thereby alleviating myocardial cell damage. Regarding ferroptosis, Res inhibits the occurrence of ferroptosis by regulating the expression of proteins related to iron metabolism. Res can also improve I/R injury through mechanisms such as activating autophagy and the mitochondrial quality control network. In regard to improving endothelial function, Res protects the function of endothelial cells by regulating multiple signaling pathways, such as downregulating the PREP1-mediated pathway. Res can also regulate lipid metabolism and inhibit the progression of atherosclerosis. In terms of inflammatory responses, Res exerts anti-inflammatory effects through mechanisms such as inhibiting the nuclear factor-kappa B(NF-κB) signaling pathway. In addition, Res has an improving effect on cardiotoxicity caused by different drugs or environmental factors. However, the clinical application of Res still faces limitations such as poor pharmacokinetic properties. In the future, in-depth exploration is needed at multiple levels from basic research to clinical application to clarify the dose-response relationship and standardize the standards of medication regimens with the expectation of providing more effective strategies for the prevention and treatment of cardiovascular diseases.
Humans ; Resveratrol/pharmacology* ; Animals ; Cardiotonic Agents/pharmacology* ; Oxidative Stress/drug effects* ; Cardiovascular Diseases/genetics* ; Cardiovascular System/metabolism* ; Signal Transduction/drug effects*

PURPOSE: To evaluate the diagnostic accuracy of the observational chart for traumatic limb swelling (OCTLS) for osteofascial compartment syndrome (OCS). METHODS: This was a descriptive-longitudinal study. Data of 316 patients who underwent surgical treatment for tibial fractures in our department from January 2015 to December 2023 were collected. Patients with Gustilo type II or higher open fractures, vascular injury, or bilateral fractures were excluded from the study. Two groups of double-blinded investigators independently assessed patients for the presence of OCS using 2 distinct diagnostic methods. Three senior orthopedic trauma surgeons evaluated patients with post-fracture calf swelling for OCS and the need for fasciotomy based on clinical signs and their extensive clinical experience. Subsequently, fasciotomy was performed according to their judgment, followed by postoperative examination of muscle and soft tissue conditions. Additionally, a follow-up evaluation was conducted to assess for complications such as ischemic muscle contracture. Another 3 trained researchers used OCTLS to grade swelling severity and determine the need for fasciotomy. The final diagnostic gold standard of OCS was determined by referring to whether there was escape of muscles at fasciotomy and/or color change in the muscles or muscle necrosis intraoperatively, and neurological abnormality or contracture at the last follow-up. The results of the 2 diagnostic methods were compared with the final diagnostic result. Kappa consistency test, paired χ² test (McNemar test), and receiver operating characteristic curve were used to evaluate the diagnostic efficacy of the 2 diagnostic methods. RESULTS: Of the 316 patients, 211 were finally included in the study, including 160 males and 51 females, with an average follow-up time of (14.5 ± 2.7) months. Among the 211 patients with tibial fracture-associated swelling, 42 were definitively diagnosed with OCS. Based on clinical symptoms and signs judgment, among the 65 fasciotomy patients, 38 were confirmed as correct, while among the 146 non-fasciotomy patients, 4 developed ischemic muscle contractures. Based on the OCTLS for assessment, fasciotomy was correctly recommended in 36 out of 43 cases, while 6 out of 168 non-fasciotomy patients developed OCS. Compared to the use of the gold standard, clinical signs judgment showed moderate consistency (McNemar's test p < 0.001, Kappa = 0.618, p < 0.001), whereas OCTLS demonstrated strong agreement (McNemar's test p = 1.000, Kappa = 0.808, p < 0.001). Receiver operating characteristic analysis revealed higher diagnostic accuracy for OCTLS (area under curve = 0.908, 95% CI: 0.843 - 0.972) compared to clinical signs judgment (area under curve = 0.872, 95% CI: 0.812 - 0.933). OCTLS achieved superior accuracy (93.8% vs. 85.3%, χ² = 8.221, p < 0.001) and a lower fasciotomy rate (20.4% vs. 30.8%, χ² = 6.023, p = 0.014). CONCLUSION Compared to clinical signs judgment, OCTLS significantly reduces unnecessary fasciotomy, improves diagnostic accuracy for OCS, and enables non-invasive, dynamic, and quantitative assessment, making it a valuable tool for clinical practice.
Humans ; Compartment Syndromes/etiology* ; Male ; Female ; Adult ; Tibial Fractures/surgery* ; Middle Aged ; Fasciotomy ; Edema/etiology* ; Longitudinal Studies ; Aged ; Young Adult

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Neuropathic pain is a chronic condition caused by damage or dysfunction in the nervous system. While the spleen may influence neuropathic pain, its role has been poorly understood. This study demonstrates that the spleen plays a crucial role in regulating neuropathic pain through the bed nucleus of the stria terminalis (BNST) - paraventricular nucleus of the hypothalamus (PVN) neural circuit in a chronic constriction injury (CCI) mouse model. Splenectomy, splenic denervation, or splenic sympathectomy significantly increased the mechanical withdrawal threshold (MWT) and reduced macrophage infiltration in the dorsal root ganglia (DRG) of CCI mice. Pseudorabies virus injections into the spleen revealed connections to the BNST and PVN in the brain. Chemogenetic inhibition of the BNST-PVN circuit increased macrophage infiltration in the DRG and decreased the MWT; these effects were reversed by splenectomy, splenic denervation, or sympathectomy. These findings underscore the critical role of the spleen, regulated by the BNST-PVN circuit, in neuropathic pain.
Animals ; Neuralgia/pathology* ; Septal Nuclei/physiopathology* ; Male ; Spleen/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiopathology* ; Mice, Inbred C57BL ; Splenectomy ; Mice ; Neural Pathways/physiopathology* ; Disease Models, Animal ; Ganglia, Spinal/physiopathology* ; Sympathectomy ; Macrophages

Objective To explore the application value of vesicourethral anastomosis with maximal urethral length preservation(MULP)and bladder neck preservation(BNP)in laparoscopic radical prostatectomy(LRP)or robot-assisted laparoscopic radical prostatectomy(RALP)for high-risk prostate cancer(HRPC)in terms of early urinary continence and oncology.Methods Clinical data of 23 HRPC patients who underwent LRP(including RALP)with MULP and BNP in our hospital during May 2022 and Jan.2024 were retrospectively analyzed.Patients'basic information,surgical parameters,postoperative complications,oncological outcomes and urinary incontinence were collected and analyzed.Results All operations were completed successfully without conversion to open surgery.The operation time was(108±31)min,average blood loss(112±45)mL,hospital stay(5.5±1.5)days,urethral catheterization time(12.6±1.8)days,and no patient received blood transfusion during operation.The urinary continence rates at the time of catheter removal,and at 1,3,and 6 months after surgery were 39.1％,65.2％,73.9％,and 91.3％,respectively.Two patients had positive margins,both of which were at the neurovascular bundle.No patient developed surgery-related complications,urinary obstruction or fistula after surgery.Conclusion Vesicourethral anastomosis with MULP and BNP in LRP for HRPC can effectively improve patients'early urinary continence rate and postoperative quality of life without increasing the oncological risk.

Chronic heart failure （CHF） is a clinical syndrome resulting from damage to the myocardium， leading to changes in the function or structure of the heart and causing reduced pumping and/or filling capacity. Its pathogenesis is complex， potentially involving myocardial fibrosis， apoptosis and autophagy of cardiomyocytes， inflammatory responses， oxidative stress， and myocardial remodeling. Our team believes that the fundamental pathogenesis of CHF is heart-Qi deficiency， with the disease location in the heart， which is closely related to other organs. Due to heart-Qi deficiency， blood circulation weakens， leading to blood stasis， which in turn generates water-dampness and phlegm turbidity that accumulate over time and become toxic. The interaction between water stasis， Qi stagnation， blood stasis， and phlegm toxicity further weakens the body， creating a vicious cycle （deficiency， stasis， water retention， and toxicity） that is difficult to resolve. Under physiological conditions， the nuclear factor-κB （NF-κB） signaling pathway functions normally， maintaining vital activities and immune responses. However， in pathological states， the NF-κB signaling pathway becomes imbalanced， triggering inflammatory responses and other issues. Research has shown that traditional Chinese medicine （TCM） can regulate the NF-κB signaling pathway through multiple pathways， targets， and effects， effectively improving the progression of CHF. As a result， this has become a research hotspot for the prevention and treatment of the disease. Guided by TCM theory， this research group reviewed the literature to summarize the activation pathways of the NF-κB pathway and its interactions with other pathways. Additionally， the group summarized the research progress on the regulation of the NF-κB pathway in the treatment of CHF using Chinese medicines， their active ingredients， Chinese medicine compounds， and Chinese patent medicines. This study is expected to clarify the mechanisms and targets by which TCM treats CHF by regulating the NF-κB pathway， thereby guiding clinical treatment and drug development for CHF.