OBJECTIVES: To explore the mechanism of cinnamic acid (CA) for improving doxorubicin-induced myocardial injury (DIC) in mice. METHODS: Network pharmacology analysis was used to obtain the key targets of CA and DIC. Male C57BL/6J mice were randomized into Sham, DOX, CA (25, 50 and 100 mg/kg)+DOX, and CA+Ferrostatin-1+DOX groups, and their myocardial function and pathology were examined by echocardiography and HE staining. Serum levels of CK-MB, LDH, MDA, IL-6, TNF‑α and myocardial ROS level were detected, and the expression levels of TLR4 and ferroptosis pathway proteins in myocardial tissue were detected by Western blotting. Cultured murine cardiomyocytes (HL-1 cells) with or without transfection with a small interfering RNA targeting TLR4 (si-TLR4) were treated with DOX or Erastin, and the cellular ROS content was measured by DCFH-DA staining; the expression level of GPX4 was detected using immunofluorescence staining. RESULTS: Network pharmacology analysis suggested that CA may improve DIC through TLR4 signaling. DOX treatment caused obvious myocardial injury in mice, which showed significantly increased serum levels of CK-MB, LDH, MDA, IL-6, TNF-α and myocardial ROS level with decreased myocardial levels of SLC7A11 and GPX4 proteins and increased levels of TLR4 and PTGS2 proteins. All these changes in the mouse models were significantly alleviated by treatment with CA, and the mice receiving CA or ferrostatin-1 treatment exhibited increased myocardial expressions of SLC7A11 and GPX4 proteins and lowered expressions of TLR4 and PTGS2 proteins. In cultured HL-1 cells, treatment with DOX and Erastin both obviously increased intracellular ROS level and decreased cellular GPX4 expression level, and these changes were strongly attenuated by TLR4 interference. CONCLUSIONS CA, as a potent herbal monomer, can effectively alleviate DIC in mice by inhibiting TLR4-mediated ferroptosis.
Animals ; Ferroptosis/drug effects* ; Toll-Like Receptor 4/metabolism* ; Myocytes, Cardiac/metabolism* ; Mice, Inbred C57BL ; Mice ; Male ; Doxorubicin/adverse effects* ; Cinnamates/pharmacology* ; Signal Transduction ; Reactive Oxygen Species/metabolism*

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

OBJECTIVE To compare the contents of schizandrin A, schizandrin B, schizandrin C, schisandrol A, schisandrol B, schisantherin A, anwuligan, and schisanhenol in Schisandrae Sphenantherae Fructus on market from 12 habitats. METHODS The samples were pre-treated by 96-well fitration plates. The assay was performed on ACE EXCEL 1.7 C18-AMIDE(100 mm×2.1 mm, 1.7 μm) column with 0.1% formic acid-water(A) and methanol(B), gradient elution, flow speed was 0.4 mL·min–1. Ion source was electric spray ion source, positive ion monitoring mode, multireaction monitoring mode for quantitative analysis. Linear, instrument precision, stability, repeatability, average recovery were investigated. RESULTS The content of schisantherin A in 10 of 12 producing areas reached the standard of ≥0.2% of Schisandrae Sphenantherae Fructus in 2020 Edition of Chinese Pharmacopoeia. CONCLUSION UHPLC-MS/MS is suitable for simultaneous determination of multiple components in Schisandrae Sphenantherae Fructus. The Schisandrae Sphenantherae Fructus in the market basically meet the national legal standards.

Purpose/Significance By integrating clinical and biological sample information,a big data research platform for biologi-cal sample information resources is built to provide one-stop data retrieval,integration and analysis services for researchers,and a data governance system is established,so as to improve the level of hospital clinical research infrastructure construction.Method/Process Common data model and data governance technology are adopted to integrate data sources from different vendors through extraction,trans-formation,loading and other steps to provide a unified data access portal.Result/Conclusion The big data research platform for biologi-cal sample information resources has the advantages of multi-dimensional data screening and rapid integrated analysis,which can pro-vide support for clinical research.

Objective:To explore the application value of multimodal MRI imaging in early neurological deterioration (END) and clinical prognosis prediction of acute ischemic stroke (AIS).Methods:A total of 200 AIS patients admitted to the Chengde Central Hospital from October 2019 to October 2022 were selected as the study subjects. Based on whether END occurred within 7 days of enrollment, there were 40 cases in the occurrence group and 160 cases in the non occurrence group. The influencing factors of END occurrence in AIS patients and the predictive value of multimodal magnetic resonance imaging (MRI) parameters on END were analyzed; According to the modified Rankin (mRS) score, patients were divided into good prognosis and poor prognosis groups, and the impact of multimodal MRI imaging parameters on the risk of poor prognosis in AIS patients was analyzed.Results:There were statistically significant differences in the apparent diffusion coefficient (ADC), cerebral blood flow (CBF), and their differences before and after thrombolysis in multimodal MRI imaging parameters between the END group and the non END group, as well as in the National Institutes of Health Stroke Scale (NIHSS) score at admission, age, and time from onset to admission (all P<0.05). The difference between ADC and CBF before and after thrombolysis, time from onset to admission, NIHSS score at admission, and age were all independent influencing factors for the occurrence of END in AIS patients (all P<0.05). The area under the curve (AUC) of the combined prediction of the difference between ADC and CBF before and after thrombolysis for the occurrence of END in AIS patients was 0.924, which was higher than that predicted by a single indicator ( P<0.05). The incidence of poor prognosis in patients with END was significantly higher than that in patients without END ( P<0.05). The risk of poor prognosis in AIS patients with a difference of less than <45.83×10 -9 mm 2/s before and after ADC thrombolysis was 3.136 times higher than that in patients with ≥45.83×10 -6 mm 2/s. The risk of poor prognosis in AIS patients with a difference of less than 10.52 ml/(min·100 g) before and after ADC thrombolysis was 2.640 times higher than that in patients with ≥10.52 ml/(min·100 g). Conclusions:Multimodal MRI imaging can be used for END evaluation in AIS patients and can provide reference for clinical prognosis evaluation.

[Objective] To investigate the correlation between human leukocyte antigen (HLA) gene polymorphism and hepatitis B virus (HBV) infection. [Methods] Venous blood samples were collected from 501 healthy individuals undergoing physical examinations at Yan’an Hospital in Kunming, Yunnan Province. Enzyme linked immunosorbent assay (ELISA) was used to detect HBV halves. Based on the results of HBV half detection, the patients were divided into three groups: HBV carrier group, previous infection group, and healthy control group. The HLA-A antigen genotype was detected using polymerase chain reaction with sequence specific primers (PCR-SSP) genotyping technology, and the distribution frequency of HLA-A gene polymorphism was compared between HBV carrier group and healthy control group, as well as between previous infection group and healthy control group. SPSS17.0 software was used for data statistical analysis. [Results] In the healthy control group, the HLA-A2 positivity rate was 47.49%, and the allele frequency was 31.29%.The overall frequency of gene distribution in the healthy control group was consistent with the HLA-A allele table commonly and confirmed in China published by the Chinese Bone Marrow Bank. The HLA-A2 positivity rate and allele frequency in the HBV carrier group were 63.04% and 42.23%, respectively; The difference in HLA-A2 positivity rate and allele frequency among carriers was statistically significant (P<0.05). the HLA-A2 positivity rate and allele frequency in the HBV previous infection group were 56.14% and 35.97%, respectively, which did not significantly differ from those in the healthy control group (P>0.05). [Conclusion] HLA-A2 gene may be a susceptibility gene for chronic hepatitis B HBV carriers.

With the development of interventional technology and the innovation of interventional instruments,neurointerventional surgery has become one of the treatments for cerebrovascular diseases.Neurointervention has the advantages of less trauma,quick recovery and fewer complications.However,due to the complexity of cerebrovascular diseases and the vascular bending and variation,neurointerventional procedures often take a long time and require general anesthesia,which makes patients prone to hypothermia during surgery.At present,clinical studies on intraoperative hypothermia mainly focus on the surgical general anesthesia,and there are few studies related to hypothermia occurring in neurointerventional procedures,to which the clinical attention has not been highly paid.This paper aims to make a comprehensive review about the hypothermia during surgery,focusing on the effect of hypothermia on the body,the characteristics of neurointerventional therapy,the causes of hypothermia,and the prevention and treatment measures of intraoperative hypothermia,so as to provide reference for the medical staff working in the neurointerventional therapy department.

Objective To investigate the puncture effect of radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale with ultrasound guidance and CT verification in the treatment of V3 branch trigeminal neuralgia(TN).Methods Forty-eight V3 branch TN patients,19 males and 29 females,aged＞18 years,BMI≤28 kg/m2,undergoing radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale were selected.Patients were divided into two groups by random number table method:ultrasound guidance combined with CT verification group(group U)and CT guidance group(group C),24 patients in each groups.According to grouping result,patients received radiofrequency ther-mocoagulation of semilunar ganglion with foramen ovale puncture performed under the ultrasound guidance and CT verification or CT guidance respectively.The success cases of puncture,the number of puncture,ra-diation dose,puncture time,operation time and the occurrence of treatment complications were recorded.Numerical rating scale(NRS)scores and Barrow neurological institute(BNI)scores were recorded before surgery,2,4,12,and 24 weeks after surgery,and good postoperative pain relief rate(BNI Ⅰ or Ⅱ)was calculated.Results All patients in both groups completed puncture operationand radiofrequency thermo-coagulation.Compared with group C,group U had fewer number of puncture,lower radiation exposure,and shorter puncture and surgical times(P＜0.05).Compared with baseline before operation,NRS scores were significantly lower in both groups at 2,4,12,and 24 weeks after surgery(P＜0.05).There was no signif-icant difference in the rate of good pain relief 2,4,12,and 24 weeks after surgery between the two groups.There was no significant difference in the incidence of facial hematoma between the two groups.No other se-rious complications were found in both groups.Conclusion Radiofrequency thermocoagulation of semilunar ganglion through the foramen ovale with ultrasound guidance and CT verification is a safe and feasible method for the treatment of the V3 branch TN.Compared with CT guidance,ultrasound guidance combined with CT verification can significantly improve the puncture accuracy and reduce the radiation exposure related to treatment.

Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.