In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

Background: s/Aims: Anti-mitochondrial M2 antibody (AMA-M2) is a specific marker for primary biliary cholangitis (PBC) and it could be also present in non-PBC individuals. Methods: A total of 72,173 Chinese health check-up individuals tested AMA-M2, of which non-PBC AMA-M2 positive individuals were performed follow-up. Baseline data of both clinical characteristics and laboratory examinations were collected in all AMA-M2-positive individuals. Least absolute shrinkage and selection operator (LASSO) regression was performed to investigate the potential variables for developing PBC. Results: A total of 2,333 individuals were positive with AMA-M2. Eighty-two individuals had a medical history of PBC or fulfilled the diagnostic criteria of PBC at baseline, and 2,076 individuals were non-PBC. After a median follow-up of 6.6 years, 0.6% developed PBC, with an accumulative 5-year incidence rate of 0.5%. LASSO regression showed that levels of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), immunoglobulin M (IgM), eosinophilia proportion (EOS%), gamma globulin percentage, and hemoglobin (HGB) were potential variables for developing PBC. Multivariate Cox regression is used to construct a predictive model based on 7 selected variables, and time-dependent receiver operating characteristic analysis showed that the area under the curve of the prediction model at 3, 5, and 10 years were, respectively, 1.000, 0.875, and 0.917. Conclusions This study offers insights into the onset of PBC among individuals who tested positive for AMA-M2 during routine health check-ups. The prediction model based on ALP, GGT, IgM, EOS%, gamma globulin percentage, HGB, and sex has a certain predictive ability for the occurrence of PBC in this population.

Objective To evaluate the effect of dapagliflozin on myocardial function in early spontaneously hypertensive rats(SHR)with layer-specific global longitudinal strain(GLS).Methods A total of 45 male SHR aged 6 weeks were randomly divided into control group(normal saline),dapagliflozin group[1 mg/(kg·day)],and losartan group[10 mg/(kg·day)].Fifteen male Wistar-Kyoto(WKY)rats at same age with normal blood pressure were subjected and served as blank control group.During 8 weeks of intervention,systolic blood pressure(SBP)was measured,and conventional echocardiography and two-dimensional speckle tracking echocardiography(2DSTE)were performed and the results were collected to acquire the longitudinal strain of each layer of left ventricular(LV)myocardium.The parameters were compared among the groups.The pathological changes of myocardium were observed in each group of rats.Results Compared with the WKY group,LV ejection fraction(LVEF)and LV fraction shortening(LVFS)at week 8 were decreased in the control group(P＜0.05),but no such decreases were observed in the dapagliflozin group and the losartan group.The GLS of endo-myocardium(GLSendo)at the 6th week was decreased,and GLSendo,GLSmid and GLSepi at the 8th week were all decreased in the control group than the WKY group(all P＜0.05).But there were no statistical differences in the above 3 indicators in the dapagliflozin and losartan groups when compared with the WKY group(all P＞0.05).The pathological results showed that myocardial interstitial fibrosis was observed in the control group at the 6th week.Conclusion Dapagliflozin can effectively improve myocardial function in early SHR.

Objective To establish a mouse model of H1N1 influenza wind-heat syndrome by combining climate intervention with influenza virus nasal drops.Methods Seventy-two BALB/c mice were divided randomly into nine groups:a Control group,wind-heat(FR)groups(FR-3Day,FR-5Day),and Model groups(1LD-3Day,2LD-3Day,3LD-3Day,1LD-5Day,2LD-5Day,2LD-5Day,3LD-5Day)(n=8 mice per group).Mice in the Control group were housed in a normal environment,while mice in the FR and Model groups were kept in wind-heat conditions for 7 d.Mice in the Model groups received nasal PR8 influenza virus infection on the 8th day,and mice in the Control and FR heat groups received equal amounts of physiological saline nasal drops.After virus challenge,each group was housed in a normal environment and samples were taken on days 3 and 5.The appearance of the mice was observed and recorded and the lung index,routine blood parameters,lung tissue pathology,serum interleukin(IL)-6 levels,and virus titers were detected in each group based on their behavioral status,stools,and body temperature.Results After 7 d of wind-heat intervention,mice in the FR groups showed no significant abnormalities in terms of appearance,stools,body temperature,routine blood parameters,or lung tissue pathology compared with the Control group.The appearance,lung index,red blood cell count,hemoglobin,hematocrit,pathological result,and body temperature in the Model groups worsened progressively with increasing time and toxin dosage,while the neutrophil percentage,lymphocyte percentage,virus titer,and serum IL-6 levels peaked on day 3 after viral attack,for the same viral dose,and then decreased slightly on day 5.Conclusions PR8 nasal drops and 7 d of wind-heat climate intervention can be used to establish a mouse model of influenza wind-heat syndrome.

Objective To investigate the clinical efficacy of internal decompression based on white matter tract preservation in the treatment of malignant middle cerebral artery infarction(MMCAI).Methods A retrospective analysis was conducted on 54 patients with MMCAI.Patients were divided into a study group(n=26)and a control group(n=28)according to the surgical approach.Patients in the study group underwent preoperative fusion of CT,CTP,DWI,and DTI imaging data within a neuronavigation system.This fusion visualized the spatial relationships between the infarct core(IC),ischemic penumbra,and the corticospinal tract(CST).Subsequently,IC resection combined with decompressive craniectomy(DC)was performed while protecting the CST.Patients in the control group underwent DC alone.Key outcome measures included:changes in fractional anisotropy(FA)within the affected CST projection area at 1 month postoperatively;and 6-month postoperative mRS score,mortality,and surgical complications at 6 months postoperatively.Results At 1 month postoperatively,FA in the affected CST projection area were significantly higher in the study group than in the control group(0.092±0.013 vs.0.082±0.008,P<0.05).At the 6-month follow-up,the postoperative mRS score in the study group was significantly lower than that in the control group[2.3(1.3,4.5)vs.3.9(2.4,5.5),P<0.05]and a lower mortality rate(11.5%vs.39.3%,P<0.05)compared to the control group.However,there were no statistically significant differences between the two groups in the incidence of postoperative intracranial hemorrhage,intracranial infection,or epilepsy(P>0.05).Conclusion Internal decompression based on white matter tract protection combined with DC can reduce mortality and contribute to improving function outcomes in patients with MMCAI.