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*

Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

Objective To observe the expression of serum carcinoembryonic antigen(CEA)and cytokeratin 19 fragment(CYFRA21-1)in peripheral blood of lung cancer patients,and to explore the prognostic value of combined imaging indicators for lung cancer patients.Methods Retrospectively analyze clinical data of lung cancer patients;all patients were followed up for six months after chemotherapy;observed the prognosis outcome of patients;included patients with cancer cell recurrence,metastasis or death in the poor prognosis group,and the rest of the patients in the good prognosis group.The baseline data,laboratory data and multi-slice spiral computed tomography(MSCT)results of the two groups before chemotherapy were compared;the application of peripheral blood biomarkers CEA and CYFRA21-1 combined with MSCT in predicting the prognosis of patients with lung cancer was analyzed.Results Among the 102 lung cancer patients who completed chemotherapy follow-up,16 had recurrence,10 had metastasis,and 5 died,accounting for 30.39％(31 cases/102 cases)of poor prognosis;the levels of CEA expression in the poor prognosis group and the good prognosis group were(28.03±8.49)and(17.03±5.78)ng·mL-1,respectively;the levels of CYFRA21-1 expression were(7.03±1.46)and(4.86±0.94)ng·mL-1,respectively;the levels of CA125 expression were(86.16±9.42)and(72.33±7.83)ng·mL-1,respectively;blood flow rates were(94.58±15.63)and(78.21±10.23)mL·s-1,respectively;surface permeability were(18.44±3.67)and(15.61±3.38)mL·min-1·100 g-1,respectively;time to peak were(26.58±5.50)and(20.15±3.49)s,respectively;tumor volume were(88.54±12.22)and(77.19±10.56)mm3,respectively;the differences between the two groups were statistically significant(all P＜0.05).The receiver operating characteristic(ROC)curve showed that the areas under the curves(AUC)of CEA and CYFRA21-1 plasma concentrations were 0.854 and 0.892;the AUC of blood flow rate,surface permeability,time to peak,and tumor volume were 0.810,0.719,0.834,and 0.744,respectively;and the AUC of the combined test was 0.954.Conclusion The levels of peripheral blood biomarkers CEA and CYFRA21-1 are highly expressed in the serum of lung cancer patients and the combination of CEA,CYFRA21-1 with imaging indicators is helpful in predicting the prognosis of lung cancer patients.

The pathogenesis of diabetic cardiomyopathy(DCM)is complex.Autophagy plays a pivotal role in the development of DCM,and whether its level is stable or not is closely related to the development of the course of DCM.Numerous active components found in traditional Chinese medicines and compound formulations have demonstrated the ability to modulate autophagy levels.These interventions occur through various mechanisms,such as hypoglycemic,anti-apoptotic,anti-inflammatory,and anti-oxidative stress pathways.By mitigating autophagy-induced myocardial damage,enhancing cardiac function,and slowing the progression of DCM,these compounds offer promising avenues for DCM management.This paper aims to consolidate and present research findings from the last 5 years.Our goal is to provide valuable insights and references for the research,development,and clinical application of Chinese medicine in the context of combating DCM.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

Mice ; Animals ; Alzheimer Disease/complications* ; Entorhinal Cortex/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Memory Disorders/etiology* ; Thalamus/metabolism* ; Disease Models, Animal

OBJECTIVE: To clarify the mechanism by which LINC01285 regulates proliferation and migration of colorectal cancer (CRC) cells and the clinical implications. METHODS: We analyzed the expression of LINC01285 in CRC tissues and normal tissues using data from Starbase public database. We also examined the expression levels of LINC01285 in 70 pairs of CRC and adjacent tissue samples collected from our center and in different CRC cell lines using RT-qPCR, and analyzed the correlation of LINC01285 expression with the clinicopathological parameters and tumor-free survival time of the patients. In CRC cell lines (SW620 and HT-29), the changes in cell proliferation, apoptosis, metastasis and epithelial-mesenchymal transition (EMT) phenotype following LINC01285 knockdown were analyzed using CCK-8 assay, flow cytometry, Transwell assay and Western blotting. RESULTS: The TCGA-COAD transcriptome sequencing data obtained from the Starbasev3.0 public database revealed a significantly higher expression level of LINC01285 in CRC tissues than in adjacent tissues (P=0.00016), which was verified by RT-qPCR results of the clinical samples (P=0.0002). In CRC patients, the expression level of LINC01285 was closely correlated with histological differentiation of the tumor (P=0.036), T classification (P=0.000), lymph node metastasis (P=0.001), TNM stage (P=0.000), Duke stage (P=0.009) and relapse-free survival (P=0.0102). In SW620 and HT-29 cells, which expressed significantly higher levels of LINC01285 than normal colorectal mucosal cells (P < 0.001), LINC01285 knockdown significantly inhibited cell proliferation (P < 0.001), increased early apoptosis, late apoptosis and total apoptosis rates (P < 0.05), suppressed cell migration and invasion (P < 0.001), upregulated the expression of E-cadherin (P < 0.001), and downregulated the expression of N-cadherin (P < 0.001). CONCLUSION The expression level of LINC01285, which modulates the EMT pathway to regulate the proliferation, apoptosis and metastasis of CRC cells, is closely correlated with the prognosis of CRC patients.
Humans ; Epithelial-Mesenchymal Transition ; Neoplasm Recurrence, Local ; HT29 Cells ; Cell Proliferation ; Colorectal Neoplasms

Objective:To analyze the clinical characteristics of adult Chinese patients with syncope.Methods:This is a cross-sectional survey study. Patients with preliminary diagnosis of syncope in the Emergency Department, Geriatrics and Cardiology Outpatient Department, or Syncope Unit of 37 hospitals in 19 provinces, autonomous regions and the Hong Kong Special Administrative Region from June 2018 to March 2021 were included in this study. The clinical features of these patients with syncope were analyzed.Results:A total of 4 950 consecutive patients with syncope were included in this study. The age was (56.3±16.8)years, and 2 604 cases (52.6%) were male. The most common type of syncope was neurally mediated syncope (2 345 (47.4%)), followed by cardiac syncope (1 085 (21.9%)), orthostatic hypotensive syncope (311 (6.3%)), and unexplained syncope accounted for nearly one third (1 155 (23.3%)). Predisposing syncope was more common in patients under 65 years of age(2 066(72.4%) vs. 786(27.6%),χ 2=136.5, P<0.001). Presyncope was more common in patients with neurally mediated syncope (1 972(79.0%) vs.1 908(73.9%), χ 2=17.756, P<0.001). Premonitory symptoms were more common in women(1 837(80.0%) vs. 1 863(73.0%),χ 2=33.432, P<0.001). Presyncope syndrome was more common in patients under 65 years of age (2 482(77.8%) vs. 1 218(73.4%),χ 2=17.523, P=0.001). Cyanosis was more common in ≥65 years old patients (271(18.2%) vs. 369(12.7%), χ 2=23.235, P<0.001). Urinary incontinence was more common in old patients aged ≥65 years(252(15.2%) vs. 345(10.8%), χ 2=19.313, P<0.001). Family history was more common in patients with cardiogenic syncope compared with other types of syncope (264(24.3%) vs. 754(19.5%), χ 2=11.899, P=0.001). Hypertention(1 480(30.5%)), coronary heart disease(1 057(21.4%)), atrial flutter and atrial fibrillation(359(7.2%)), second degree atrioventricular block(236(4.8%)) were common complications of syncope. The proportion of patients with coronary heart disease was significantly higher in cardiac syncope than that of other types of syncope(417(38.4%) vs. 640(16.6%), χ 2=241.376, P<0.001). Other common complications included cerebrovascular diseases (551 (11.1%)) and diabetes mellitus (632(12.8%)). Conclusions:Neurally mediated syncope is the most common syncope in adult Chinese population. Patients with predisposing conditions and premonitory conditions are younger. Presyncope is more common in women. The proportion of family history and coronary heart disease is higher in patients with cardiogenic syncope.

Introduction: Non-adherence to antihypertensive medications is a leading cause of uncontrolled hypertension and its complications. However, data on the factors associated with non-adherence to antihypertensive medications in the communities of Sarawak, Malaysia, are limited. This study aimed to examine the prevalence and determinants of medication non-adherence among patients with uncontrolled hypertension. Methods: A cross-sectional study was conducted using the systematic sampling method in four government primary healthcare clinics in Sarawak. A self-administered questionnaire was used to obtain socio-demographic data and evaluate non-adherence. Blood pressure was measured, and relevant clinical variables were collected from medical records. Multivariate logistic regression was used to determine the determinants of medication non-adherence. Results: A total of 488 patients with uncontrolled hypertension were enrolled in this study. The prevalence of medication non-adherence was 39.3%. There were four predictors of medication non-adherence among the patients with uncontrolled hypertension: tertiary educational level (odds ratio [OR]=4.21, 95% confidence interval [CI]=1.67–10.61, P=0.010), complementary alternative medication (OR=2.03, 95% CI=1.12–3.69, P=0.020), non-usage of calcium channel blockers (OR=1.57, 95% CI=1.02–2.41, P=0.039) and 1 mmHg increase in the systolic blood pressure (OR=1.03, 95% CI=1.00–1.05, P=0.006). Conclusion Because of the high prevalence of medication non-adherence among patients with uncontrolled hypertension, primary care physicians should be more vigilant in identifying those at risk of being non-adherent. Early intervention should be conducted to address non-adherence for blood pressure control.
Patient Compliance ; Hypertension ; Primary Health Care ; Malaysia