High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.

OBJECTIVE: To explore clinical effects of bone setting manipulation combined with pry reduction and Kirschner needle internal fixation in treating SandersⅡ-Ⅲ calcaneal fracture. METHODS: Clinical data of 52 patients with types Sanders Ⅱand Ⅲ calcaneal fracture (foot) treated with bone-setting manipulation combined with pry reduction and Kirscher needle internal fixation from July 2017 to July 2019 were retrospectively analyzed, including 43 males and 9 females, aged from 31 to 72 years old with an average of (50.83±10.48) years old; 15 patients with Sanders typeⅡ and 37 patients with Sanders type Ⅲ. The changes of Bühler angle, Gissane angle, calcaneus width and calcaneus height before operation and 24 months after operation were compared, and Maryland foot function score was performed to evaluate clinical effects. RESULTS: All patients were followed up from 24 to 60 months with an average of (41.50±9.86)months. The fracture healed normally and the healing time was (11.00±0.95) weeks. Bühler angle, Gissane angle, calcaneal bone width and calcaneal bone height were increased from (16.37±8.36)°, (96.27±9.62)°, (46.82±4.67) mm, (38.41±3.58) mm before operation to (31.48±8.24)°, (111.62±8.69)°, (42.06±4.83) mm, (44.21±3.82) mm at 24 months after operation, and the difference were statistically significant (P<0.01). Postoperative Maryland score at 24 months was (93.04±8.83), 40 patients got excellent result, 7 good and 5 fair. CONCLUSION Orthopedic manipulation combined with percutaneous reduction and Kirschner wire internal fixation could significantly improve Bühler angle, Gissane angle, width, and height of Sanders typeⅡ and Ⅲ calcaneal fractures, and the curative effect is satisfactory.
Humans ; Male ; Female ; Calcaneus/surgery* ; Middle Aged ; Fracture Fixation, Internal/methods* ; Adult ; Aged ; Fractures, Bone/therapy* ; Retrospective Studies ; Bone Wires ; Manipulation, Orthopedic/methods*

This study examines the effects of zearalenone(ZEA)on the survival and function of lu-teinized granulosa cells,and studies the role of activating transcription factor 6(ATF6)in regula-ting apoptosis and functional abnormalities of luteinized granulosa cells induced by ZEA.An in vitro model of luteinized granulosa cells was utilized to examine the effects of ZEA treatment on apoptosis,hormone secretion,and the expression of relevant proteins.Furthermore,the expression of ATF6 was manipulated using siRNA to elucidate its regulatory function in the ZEA-induced damage of luteinized granulosa cells in mice.Our findings revealed that ZEA inhibited the activity of luteinized granulosa cells and reduced the secretion of estradiol(E2)and progesterone(P4)in a dose-dependent manner.The expression levels of p-IRE1,ATF6 and StAR in both low(20 pmol/L)and high(40 μmol/L)ZEA groups were significantly increased after 24 h(P＜0.05).GRP78 had no significant change at low concentration treatment(P＞0.05),but significantly increased at high concentration treatment(P＜0.05).Similarly,ATF4 and p-EIF2α had no significant change at low concentration treatment(P＞0.05),but significantly decreased at high concentration treat-ment(P＜0.05).HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).After 48 h of treatment,ATF6 and GRP78 were significantly increased in both low and high concentration treatments(P＜0.05).p-IRE1 was significantly de-creased at low concentration treatment(P＜0.05),but remained unchanged at high concentration treatment(P＞0.05).ATF4,p-EIF2α,HSD3B2 and CYP19A1 were significantly decreased in both low and high concentration treatments(P＜0.05).St AR was significantly increased in both low and high concentration treatments(P＜0.05).Interference with the expression of ATF6 could sig-nificantly reduce the apoptosis induced by low concentration group(P＜0.05),and enhanced the hormone secretion in both high and low concentration groups(P＜0.05).In conclusion,ZEA can cause damage to luteinized granulosa cells and activate ATF6 signaling pathway.Interference with ATF6 can alleviate apoptosis and hormone secretion disturbance induced by low concentration ZEA,but has limited effect on damage caused by high concentration ZEA.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Objective:To preliminarily explore whether sirtuin1 (SIRT1) activation can inhibit neuronal ferroptosis in rats after traumatic brain injury (TBI) by regulating hypoxia-inducible factor-1α (HIF-1α)-mediated glycolysis.Methods:(1) Six SD rats were randomly divided into sham-operated group and TBI group, with 3 rats in each group; TBI model in the TBI group was established by hydraulic impact method, and rats in the sham-operated group underwent same surgery without impact. Cortical tissues of the two groups were sent for tandem mass tag (TMT) labeled quantitative proteomics detection to analyze the differential expression proteome; Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to detect pathway enrichment of the screened differential proteins. (2) Twelve SD rats were randomly divided into sham-operated group and 1-day, 3-day and 7-day post-TBI groups, with 3 rats in each group. Treatment methods were the same as above; Western blotting was used to detect SIRT1 protein expression. (3) Forty-eight rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+SIRT1 agonist group, with 12 rats in each group; rats in the sham-operated group and TBI group accepted treatment as above; rats in the TBI+SIRT1 agonist group were intraperitoneally injected with SRT1720 (dissolved in ≤ 5% dimethyl sulfoxide, at a dose of 20 mg/kg) within 30 minutes after modeling, twice a day (with an interval of 12 hours); and rats in the TBI+vehicle group were injected with same dose of dimethyl sulfoxide at the same time. One d after modeling, neurological deficit was assessed using modified Neurological severity score (mNSS), brain water content was measured by dry-wet weight method, histopathological changes in the cortical lesions were observed by HE staining, mitochondrial ultrastructure was examined by transmission electron microscopy, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the brain tissues were detected by colorimetry, and protein expressions of SIRT1, HIF-1α (key protein in the glycolytic pathway), glutathione peroxidase 4 (GPX4, key protein in the ferroptosis pathway), and acyl-CoA synthetase long-chain family member 4 (ACSL4, key protein in the ferroptosis pathway) were evaluated by Western blotting.Results:(1) KEGG analysis revealed that the glycolysis pathway and HIF-1 signaling pathway were obviously enriched in the cortical tissues of rats in the TBI group compared with the sham-operated group; GSEA showed that the HIF-1 signaling pathway (mmu04066) and ferroptosis pathway (mmu04216) gene sets in the cortical tissues of rats in the TBI group exhibited enrichment trends compared with those in the sham-operated group. (2) Compared with the sham-operated group, the 1-day, 3-day, and 7-day post-TBI groups had significantly decreased SIRT1 protein expression ( P<0.05), with the most prominent decline in 1-day post-TBI group. (3) Compared with the TBI+vehicle group, rats in the TBI+SIRT1 agonist group showed significantly reduced mNSS score and brain tissue water content (9.83±1.17 vs. 7.66±1.21; [83.62±0.91]% vs. [80.09±0.68]%, P<0.05). HE staining indicated clearer structure of the cortical area at the injury sites, and improved neuron morphology in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group; and transmission electron microscopy showed reduced mitochondrial shrinkage and partial restoration of cristae structures in the TBI+SIRT1 agonist group compared with those in the TBI+vehicle group. Compared with the TBI+vehicle group, the TBI+SIRT1 agonist group exhibited significantly decreased MDA content ([62.72±9.20] nmol/g vs. [39.34±3.48] nmol/g), increased SOD activity ([1.95±0.23] U/mg vs. [2.48±0.14] U/mg), elevated GPX4 protein expression (0.37±0.04 vs. 0.46±0.03), and decreased HIF-1α and ACSL4 protein expressions (1.16±0.15 vs. 0.81±0.12; 1.14±0.06 vs. 1.29±0.04), with significant differences ( P<0.05). Conclusion:SIRT1 activation can exert neuroprotective effect by inhibiting HIF-1α-mediated glycolysis and reducing neuronal ferroptosis after TBI.