Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

OBJECTIVE: To evaluate the short-and medium-term efficacy of posterior medial branch block in the treatment of persistent pain after percutaneous vertebral augmentation. METHODS: From January 2018 to January 2023, a total of 1, 062 patients with osteoporotic vertebral compression fractures underwent percutaneous vertebral augmentation. Among them, 32 elderly patients who experienced persistent low back pain after surgery and subsequently received posterior medial branch block and cryoablation were included. Six patients died during follow-up, leaving 26 patients for final analysis (1 male, 25 females). The mean age was (82.96±5.66) years (ranged, 76 to 94 years). The mean body mass index was (23.76±3.08) kg·m^-2(ranged 18.1 to 27.2 kg·m^-2). The bone mineral density T-value ranged from -2.5 to -4.3 with a mean of (-3.09±0.56). The mean volume of bone cement injected was 6.00 (5.38, 7.00) ml. Fracture locations were T₁₁ (2 cases), T₁₂ (7 cases), L₁ (10 cases), L₂ (6 cases), and L₃ (1 case). The mean interval from vertebral augmentation to block treatment was (7.12±2.22) months (rangd 6 to 12 months). The vertebral augmentation procedures were percutaneous kyphoplasty(PKP) in 12 cases and percutaneous vertebroplasty (PVP) in 14 cases. At the 2nd week, 3rd month, and 6th month after the block, the numerical rating scale(NRS), Oswestry disability index(ODI), patient satisfaction, and pain relief rate at the 6th month were evaluated. Relationships between pain relief rate at the 6th month after the last treatment and possible influencing factors were analyzed. RESULTS: Compared with X-ray films after percutaneous vertebral augmentation, the X-ray films before block showed an increase in kyphotic angle and vertebral compression rate, with statistically significant differences(P<0.05). At the 2nd week, 3rd month, and 6th month after posterior medial branch block and cryoablation, NRS and ODI scores were significantly lower than before the block(P<0.05). Among the 26 patients, 5 received additional cryoablation. At the 6th month after the last treatment, 19 patients reported excellent or good satisfaction. Univariate binary Logistic analysis showed all P>0.05, and no independent factor affecting final satisfaction or pain relief at 6 months after the last treatment was identified. CONCLUSION Posterior medial branch block(with cryoablation) can effectively improve short-and medium-term symptoms and function in patients with persistent axial low back pain after percutaneous vertebral augmentation for osteoporotic vertebral fractures.
Humans ; Male ; Female ; Aged ; Spinal Fractures/surgery* ; Aged, 80 and over ; Osteoporotic Fractures/surgery* ; Vertebroplasty/adverse effects* ; Nerve Block/methods*

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Objective To comparatively analyze the clinical characteristics of primary bilateral macronodular adrenal hyperplasia(PBMAH)and adrenal cortisol-producing Adenoma(CPA),and enhance the understanding of two diseases.Methods The clinical data of 85 PBMAH patients(PBMAH group)and 195 CPA patients(CPA group)diagnosed at Department of Endocrinology,the First Medical Center of Chinese PLA General Hospital,from September 2014 to August 2024 were retrospectively analyzed.The demographic characteristics,comorbidities,biochemical indicators,adrenocorticotropic hormone-cortisol(ACTH-F)levels,and adrenal imaging features and treatment conditions were compared between the two groups.Results(1)General characteristics:Compared with CPA group,PBMAH group had older age at diagnosis and a higher proportion of male patients.(2)Clinical characteristics:Compared with CPA group,PBMAH group had a longer disease duration,a higher proportion of subclinical Cushing's syndrome(CS),and a higher proportion of hypertension,impaired glucose tolerance/diabetes,bone mass reduction or osteoporosis,with higher serum potassium levels,and the differences were statistically significant(P<0.01).(3)Hormone levels:Both PBMAH and CPA groups showed ACTH-F rhythm disorder,significantly increased cortisol levels and suppressed ACTH.Compared with PBMAH group,CPA group had stronger autonomous cortisol secretion ability,manifested by increased midnight serum cortisol(F0:00),16:00 serum cortisol(F16:00),24-hour urinary free cortisol(24 h UFC)levels and lower 8:00 serum ACTH(ACTH8:00)and 16:00 serum ACTH(ACTH16:00)(P<0.01).After low-dose dexamethasone suppression test(LDDST),CPA group showed lower suppression rates of ACTH and cortisol,and higher proportions of paradoxical elevation in serum cortisol and 24 h UFC compared with PBMAH(P<0.01).Conclusions PBMAH has a longer disease course and higher proportions of comorbid metabolic disorders than CPA,mostly manifested as subclinical Cushing's syndrome.CPA has stronger autonomous cortisol secretion ability,with cortisol less likely to be suppressed after LDDST and more obvious paradoxical elevation of cortisol and 24 h UFC.

Objective:To investigate the protective effect of N-acetylcysteine (NAC) against α-amanitin (α-AMA)-induced liver injury via regulation of mitochondrial dynamic imbalance.Methods:Thirty-two ICR mice were randomly (random number) assigned to four groups ( n = 8 per group): normal control, NAC control, α-AMA poisoning, and α-AMA + NAC treatment group. After modeling, behavioral changes were observed and survival curves were plotted. Liver function markers and oxidative stress indicators were measured using ELISA. Pathological damage in liver tissue was examined, and mitochondrial ultrastructural changes were observed via transmission electron microscopy, followed by mitochondrial injury scoring. Survival rates were analyzed using the Kaplan–Meier method. One-way ANOVA was used for intergroup comparisons, followed by pairwise comparisons. Results:Compared with the control group, α-AMA intoxication significantly reduced survival rates and increased serum ALT and AST levels ( P < 0.05). Liver tissues exhibited disordered hepatic cord arrangement, cytoplasmic loosening, and edema. Mitochondria showed moderate to severe swelling, cristae fragmentation, matrix dissolution, and vacuolation, along with increased injury scores ( P < 0.05). Oxidative markers MDA and ROS were elevated, while antioxidant enzymes SOD and CAT were decreased (all P < 0.05). Mitochondrial activity was impaired, expression of fusion proteins OPA1, MFN1, and MFN2 was downregulated, and fission protein DRP1 was upregulated (all P < 0.05). Compared with the α-AMA group, NAC treatment significantly improved survival, reduced ALT and AST levels ( P < 0.05), alleviated pathological and mitochondrial ultrastructural damage, decreased MDA and ROS, increased SOD and CAT (all P < 0.05), enhanced mitochondrial activity, upregulated OPA1, MFN1, and MFN2, and downregulated DRP1 (all P < 0.05). No significant differences were observed between the normal and NAC control groups. Conclusions:NAC may attenuate α-AMA-induced acute liver injury by maintaining mitochondrial dynamic homeostasis.

Objective:To screen the differentially expressed genes(DEGs)under high phosphate-induced calcification in the vascular smooth muscle cells(VSMCs)by mRNA high-throughput sequencing technology,and to analyze the key genes and signaling pathways involved in the VSMCs calcification.Methods:The human VSMCs were divided into control group and model group.The cells in model group was exposed to the high-phosphate medium,while the cells in control group were cultured in DMEM supplemented with 10%fetal bovine serum under the same conditions.The VSMCs in two groups,stably transfected,were cultured for 12 d.The morphology of the cells in two groups were observed and photographed under inverted microscope.The DEGs were selected by Hisat2 software,and Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by Stringtie software from three aspects,such as biological processes(BP),molecular functions(MF),and cellular components(CC).The calcification of the cells in two groups was observed by Von Kossa staining method.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to analyze the expression levels of alkaline phosphatase(ALP),bone morphogenetic protein 2(BMP2),alpha-smooth muscle actin(α-SMA),tumor protein 53(Tp53),glutathione peroxidase 4(GPX4),ferritin light chain 1(Ftl1),and glycosylphosphatidylinositol-specific phospholipase D1(GPLD1)mRNA in the cells in two groups.Results:Compared with control group,there were 2 524 DEGs in the cells in model group,and there were 1 368 upregulated DEGs and 1 156 downregulated DEGs.Clustering of DEGs between the cells in two groups was distinct.The GO functional and KEGG pathway enrichment analysis results showed that the upregulated DEGs were primarily involved in regulating the microtubule cytoskeleton,cell polarity,protein localization,and cell cycle regulation among BPs;in constructing cell membrane,microtubule organization,chromosomes,and kinetochore among CCs;and functioning in phosphatidylinositol phosphate,Rho GTPase protein binding,transmembrane transport,and protein kinase regulatory activity among MFs.Downregulated DEGs were mainly involved in cytoplasmic translation,protein membrane localization,mRNA metabolism,and protein endoplasmic reticulum localization among BPs;in forming ribosome subunits,cell membrane,and autophagy among CCs;and functioning in single-stranded DNA,ribonucleoprotein complex,growth factor binding,regulating protein kinase activity,and catalytic activity among MFs.Seven signaling pathways were significantly enriched in upregulated genes,most notably in the biosynthesis of glycosylphosphatidylinositol(GPI)anchors;whereas 18 signaling pathways were significantly enriched in the downregulated genes,most notably in ferroptosis.The RT-qPCR results showed that compared with control group,the expression levels of GPX4,Ftl1,and Tp53 mRNA in the cells in model group were significantly decreased(P<0.01),while the expression level of GPLD1 mRNA was significantly increased(P<0.01);compared with control group,the expression level of α-SMA mRNA in the cells in model group was significantly decreased(P<0.01),and the expression levels of ALP and BMP2 mRNA were significantly increased(P<0.01).Conclusion:The VSMCs underwent calcification and normal cells exhibit the DEGs.The key signaling pathways in the calcification induced by high phosphate in the VSMCs include ferroptosis and GPI anchor biosynthesis,mediated primarily through GPX4,Ftl1,Tp53,and GPLD1.

Teaching clinics represent a unique form of outpatient training of resident physicians and serve as a crucial instrument and core component of standardized training of general practice residents. This article reviews the common model and innovations of teaching clinics of general practice in China, and analyzes their reported effectiveness in enhancing the capabilities of consultation of resident physicians, the teaching capabilities of general practice trainers, as well as satisfaction levels of involved participants. It outlines the challenges encountered in implementing teaching clinics, including inadequate teaching facilities and equipment, incomplete incentive system for teaching, difficulties in patient recruitment, and weaknesses in the teaching capabilities of trainers. To address these challenges, this article proposes corresponding strategies based on realistic needs, including the improvement of facilities and equipment in teaching clinics, the establishment of incentive systems for teaching clinics, the expansion of patient recruitment channels for teaching clinics, and the enhancement of training for trainers' teaching capabilities. This is envisaged to provide both theoretical bases and practical guidance for the effective execution and standardized development of teaching clinics in general practice residency training bases.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.