ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point， this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding， 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups （10 mice per group）： The 12-month-old control group （12MCON）， the 15-month-old control group （15MCON）， and the 15-month-old group with a high-fat diet （15MHFD）. The 12MCON and 15MCON groups were continuously fed a standard diet， while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups （10 mice per group）： the 20-month-old control group （20MCON）， the model group， and the low-， medium-， and high-dose Liangyi Paste groups （2.91 ， 5.82 ， 11.64 g·kg^-1·d^-1， respectively）. The 20MCON group was continuously fed a standard diet， while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age， the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage， while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage （when the mice reached 20 months of age）， tissue samples were collected. Hepatic TG levels were measured using assay kits； liver histology and lipid deposition were observed via hematoxylin-eosin （HE） and oil red O staining； reactive oxygen species （ROS） were detected by enzyme-linked immunosorbent assay （ELISA）； Cu²⁺， superoxide dismutase （SOD）， and malondialdehyde （MDA） levels were measured by colorimetry； mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction（Real-time PCR） and Wes automated protein expression system. ResultsCompared with 12MCON， the 15MCON group showed significantly increased hepatic TG， Cu²⁺， ROS， and MDA levels （P<0.01）， decreased SOD （P<0.01）， hepatocyte swelling， and disordered arrangement. The mRNA and protein levels of ferredoxin 1 （FDX1）， dihydrolipoamide S-acetyltransferase （DLAT）， heat shock protein 70 （HSP70）， dihydrolipoamide dehydrogenase （DLD）， pyruvate dehydrogenase E1 subunit-β （PDHB）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and peroxisome proliferator-activated receptor γ （PPARγ） were significantly elevated （P<0.05， P<0.01）. Compared with 15MCON group， the 15MHFD and 20MCON groups exhibited further increases in TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group， and no significant lipid deposition was observed in the 20MCON group. FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and protein levels were significantly increased （P<0.05， P<0.01）. Compared with 20MCON group， the model group demonstrated markedly elevated TG， Cu²⁺， ROS， and MDA （P<0.01）， reduced SOD （P<0.01）， severe hepatic steatosis， and upregulated expression of FDX1， DLAT， HSP70， DLD， PDHB， Nrf2， and PPARγ mRNA and proteins （P<0.05， P<0.01）. All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.

BACKGROUND:Studies have shown that metformin has anti-inflammatory,anti-tumor,anti-aging and vasoprotective effects,and can inhibit the progression of osteoarthritis,but its specific mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism of metformin on cartilage protection in a rat model of osteoarthritis. METHODS:Forty male Sprague-Dawley rats were randomly divided into four groups(n=10 per group):blank,control,sham-operated,and metformin groups.The blank group did not undergo any surgery.In the sham-operated group,the joint cavity was exposed.In the model group and the metformin group,the modified Hulth method was used to establish the osteoarthritis model.At 1 day after modeling,the rats in the metformin group were given 200 mg/kg/d metformin by gavage,and the model,blank,and sham-operated groups were given normal saline by gavage.Administration in each group was given for 4 weeks consecutively.Hematoxylin-eosin staining,toluidine blue staining,and safranin O-fast green staining were used to observe the morphological structure of rat knee joints.Immunohistochemical staining and western blot were used to detect the protein expression of SOX9,type Ⅱ collagen,a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),Beclin1,P62,phosphatidylinositol 3-kinase(PI3K),p-PI3K,protein kinase B(AKT),p-AKT,mammalian target of rapamycin(Mtor),and p-Mtor in rat cartilage tissue. RESULTS AND CONCLUSION:The results of hematoxylin-eosin,toluidine blue and safranin O-fast green staining showed smooth cartilage surface of the knee joints and normal histomorphology in the blank group and the sham-operated group,while in the model group,there was irregular cartilage surface of the knee joint and cartilage damage,with a decrease in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.In the metformin group,there was a significant improvement in the damage to the structure of the cartilage in the knee joints of the rats,and the cartilage surface tended to be smooth,with an increase in the number of chondrocytes and the content of proteoglycans in the cartilage matrix.Immunohistochemistry staining and western blot results showed that compared with the control and sham-operated groups,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the model group was significantly decreased(P<0.05).Conversely,the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly increased(P<0.05).Furthermore,compared with the model group,the expression of SOX9,type Ⅱ collagen,and Beclin1 proteins in the cartilage tissue of rats in the metformin group was significantly increased(P<0.05),while the expression of ADAMTS5,P62,as well as p-PI3K,p-AKT,and p-Mtor proteins was significantly decreased(P<0.05).To conclude,Metformin can improve the autophagy activity of chondrocytes and reduce the degradation of cartilage matrix in osteoarthritis rats by inhibiting the activation of PI3K/AKT/Mtor signaling pathway,thus exerting a protective effect on articular cartilage.

Objective To analyze the influencing factors for carotid plaque formation in patients with essential hypertension(EH)with LASSO-Cox regression.Methods A retrospective analysis was conducted on 325 patients with new-onset hypertension admitted to the First Affiliated Hos-pital of Zhengzhou University from March 2020 to March 2021.Among them,308 completed a fol-low-up of 2-year,and then according to carotid plaque occurred or not(the carotid intima-media thickness≥1.5 mm),they were divided into in the occurrence group(85 cases)and non-occur-rence group(223 cases).Clinical data and circular RNA expression level were compared between the two groups.LASSO regression model was used to screen out the predictors of carotid plaque formation,and Cox regression model was employed to explore the influencing factors of the for-mation.Results The occurrence group had significantly advanced age,higher body mass index and CIMT,larger proportion of diabetes mellitus,and elevated serum uric acid and homocysteine(Hey)levels,but lower high-density lipoprotein cholesterol(HDL-C)than the non-occurrence group(P＜0.01).In addition,the expression levels of has-circ-0105130,has-circ-0109569,has-circ-0072659,has-circ-0079586 and has-circ-0064684 were obviously higher in the occurrence group than the non-occurrence group(P＜0.01).Multivariate Cox regression analysis showed that has-circ-0109569 and Hcy were independent risk factors for carotid plaque formation(P＜0.05,P＜0.01),and HDL-C was an independent protective factor(P＜0.01).The AUC value of for the combination of has-circ-0109569,HDL-C and Hcy in prediction of carotid artery plaques was 0.977(95％CI:0.953-0.991,P＜0.01).Conclusion High has-circ-0109569 and Hcy and low HDL-C levels are risk factors for carotid plaque formation in the EH patients.

Objective:To retrospectively analyze the cases of inflammatory myofibroblastic tumor (IMT) involving the sinonasal skull base, and to investigate their clinical characteristics, diagnostic approaches, and treatment outcomes, in order to improve understanding of this rare entity.Methods:Clinical data from five patients with pathologically confirmed sinonasal skull base IMT who underwent surgical treatment at Xiangya Hospital of Central South University between April 2010 and June 2023 were reviewed. Information on clinical presentation, laboratory findings, imaging features, histopathological and immunohistochemical results, treatment strategies, and follow-up outcomes was collected. A comprehensive analysis was performed in combination with a literature review to summarize the clinical features, diagnostic methods, and therapeutic approaches for sinonasal skull base IMT.Results:The five patients (aged 18 to 68 years) were all diagnosed based on histopathological and immunohistochemical examinations. The lesions primarily involved the nasopharynx, clivus, sphenoid sinus, and maxillary sinus. Major clinical symptoms included nasal obstruction, headache, blood-tinged nasal discharge, and facial numbness or pain. All patients underwent surgical resection; two of them also received adjunctive glucocorticoid therapy. During follow-up ranging from 1 to 143 months, two patients experienced tumor recurrence, three patients had no recurrence with significant symptomatic improvement.Conclusions:Histopathology combined with immunohistochemistry is critical for the diagnosis of sinonasal skull base IMT. Complete surgical excision when feasible remains the primary treatment strategy.

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Didangtang is a classic formula for treating blood stasis and heat， as recorded in the Treatise on Febrile Diseases， and it has been highly praised by medical practitioners throughout history. It has been recorded in many traditional Chinese medical texts and used to this day. This article comprehensively examined the records of Didangtang in different ancient versions of Treatise on Febrile Diseases by excavating and sorting out related ancient medical books and modern literature. It also investigated the dosage unit measurement， preparation method， and content of the formula in medical books throughout history. The article provided a detailed summary and exploration of the origins and processing methods of rhubarb， peach kernels， leeches， and flies in the formula. At the same time， it reviewed the clinical practice of Didangtang by medical practitioners throughout history in relevant medical books， mainly including the adjustment of dosage forms， the increase or decrease in medicinal taste and dosage， the expansion of clinical application， and the creation and elucidation of similar formulas. Although there may be differences in the above information among medical practitioners throughout history， the basic idea of attacking blood stasis and heat is consistent. In addition， based on clinical practice， the author adhered to the principle of treating stasis and heat disease as the first reference when using Didangtang. It was suggested that blood should be circulated instead of stopping in the treatment of stasis and heat accumulation syndrome. At the same time， it was believed that the use of the method of attacking stasis and heat to regulate brain diseases and mental illnesses derives from the fact that removing stasis and generating new energy can nourish the heart and mind， providing ideas for the treatment of such diseases with Didangtang. On this basis， modern clinical and animal experiments have shown that Didangtang has certain effects in improving microcirculation disorders， regulating blood rheology and hemodynamics， enhancing insulin resistance， and inhibiting inflammatory reactions. This may be an important mechanism for the formula to ''conquer blood stasis and heat''. This article explored the textual research and clinical mechanism of Didangtang， presenting facts and evidence， so as to provide a reference for the clinical application of Didangtang and the research on other prescriptions.

ObjectiveTo understand the epidemic characteristics of influenza in Beijing from 2023 to 2024, and to provide a scientific basis for the prevention and control of influenza. MethodsData on influenza-like illness (ILI) from secondary level and above hospitals, etiology surveillance data, and influenza clusters outbreaks data from 2023‒2024 were used to analyze the epidemic trend and pathogenic characteristics of influenza. Furthermore, an influenza comprehensive index was used to categorize the epidemic intensity at the severity level. ResultsA total of 2 065 857 ILI cases were reported in 2023‒2024 epidemic season, and the percentage of ILI was 3.67%. The age group of 5‒14 years accounted for the highest proportion of ILI (30.48%). A total of 41 766 throat swabs from ILI were detected, with a positive rate of 17.28%.A (H3N2) (51.86%) and B Victoria (41.93%) were the most prevalent subtypes of influenza virus. Clustered influenza outbreaks occurred mainly in primary schools (57.78%) and middle schools (35.55%), mainly caused by the influenza A (H3N2) subtype (85.93%). According to the influenza comprehensive index (I), the period of influenza activity and above (I>0.5) lasted for a total of 37 weeks, accounting for 71.15% of the entire influenza season. ConclusionCompared with previous years, the epidemic level of influenza in Beijing was increased in 2023‒2024, and the peak time became earlier. The comprehensive index method can objectively evaluate the level of influenza epidemic and provide suggestions for the future prevention and control of influenza in Beijing.

As a type of acute cerebrovascular disease,stroke is one of the most common fatal and disabling diseases in the world,which seriously threatens the quality of life of patients;however,there are still limited treatment methods for this disease in clinical practice.Traditional Chinese medicine(TCM)has a long history and good efficacy in the treatment of stroke,and the active components of TCM can alleviate nerve injury caused by stroke by improving the development and progression of various pathophysiological mechanisms such as nerve inflammation,oxidative stress,and blood-brain barrier damage.This article reviews the role of active components of TCM in the treatment of ischemic stroke,in order to provide more ideas and options for the clinical treatment of this disease in the future.

Objective:To investigate the clinical diagnosis and treatment of IgG4-related disease（IgG4-RD） primarily involving the nasal cavity and skull base. Methods:A retrospective analysis was conducted on the clinical data of 8 patients with IgG4-RD primarily involving the nasal cavity and skull base who visited the Nasal and Skull Base Surgery Department at Xiangya Hospital from October 2017 to January 2024. The cohort comprised 4 males and 4 females, aged 8 to 69 years. Clinical data, laboratory examination results, imaging findings, histopathological results, and treatment plans were collected. The clinical manifestations, diagnosis, treatment and follow-up results of IgG4-RD primarily involving nasal cavity and skull base were summarized and previous literature were also reviewed. Results:The initial symptoms in the 8 patients included nasal congestion, headache, sensory function decline, and facial deformities. Three patients also had parotid and pulmonary involvement. Among the 8 patients, 4 underwent partial surgical resection combined with glucocorticoid therapy; 1 underwent partial surgical resection combined with glucocorticoid and immunosuppressant therapy; 1 received glucocorticoid therapy alone; and 2 received glucocorticoid combined with immunosuppressant therapy. Follow-up was conducted one month after treatment, lasting from 5 to 79 months. During the follow-up period, recurrence was observed in 1 patient treated with glucocorticoid combined with immunosuppressants and in 1 patient treated with glucocorticoid alone, while the other 6 patients achieved significant remission. Conclusion:The diagnosis of nasal cavity and skull base IgG4-RD requires the combination of histopathology, laboratory tests, and imaging results. Treatment primarily includes glucocorticoids or combined immunosuppressants. For patients with significant compression symptoms, sensory function impairment, or facial deformities, surgical resection is an important treatment option. Given the high risk of recurrence, early intervention, active treatment, and long-term follow-up are crucial.
Humans ; Male ; Skull Base/pathology* ; Female ; Middle Aged ; Retrospective Studies ; Aged ; Nasal Cavity/pathology* ; Adult ; Immunoglobulin G4-Related Disease/therapy* ; Immunoglobulin G ; Child ; Young Adult ; Adolescent