Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans ; Proteomics/methods* ; Biomarkers/blood* ; Adolescent ; Young Adult ; Apolipoprotein A-I/blood* ; Machine Learning ; Tuberculosis/blood* ; Proteome/analysis* ; Male ; Hemoglobins/analysis* ; Female ; Blood Proteins/analysis* ; Adult

Objective To establish a reference interval for the pepsinogen(PG)Ⅰ,PGⅡ and PGⅠ/PGⅡ in healthy adult subjects in Zhejiang Province.Methods The data of 45 504 healthy adult subjects were collected,and the levels of serum PGⅠ and PG Ⅱ were detected by chemiluminescence microparticle immunoassay.The reference range of PGs were determined according to the CLSI-C28-A3 file.Results The median serum PGⅠ concentration in male was 132.62μg/L,PGⅡ concentration was 8.10μg/L,and PGⅠ/PGⅡ was 15.9.For females,they were 107.44μg/L,6.96μg/L and 15.0,respectively.PGI,PGⅡ concentration and PGⅠ/PGⅡ ratio were significantly higher in males than in females(P<0.001).The levels of PGⅠ and PGⅡ increased with age(P<0.001).Serum PGⅠ reference interval for male:59.79-234.97μg/L for 19-39 years old,63.33-294.62μg/L for 40-59 years old,64.25-333.61μg/L for≥60 years old,PGⅡ reference interval:3.33-22.60μg/L for 19-39 years of age,3.79-33.89μg/L for 40-59 years of age,4.15-42.08μg/L for≥60 years of age,PGⅠ/PGⅡ reference interval:those aged 19-39 years ranged from 7.3 to 31.4,those aged 40-59 years ranged from 5.8 to 30.9,and those aged≥60 years ranged from 3.9 to 30.7.The reference intervals of female PGⅠ were 48.79-215.68μg/L,52.10-276.01μg/L,and 64.34-317.20μg/L,respectively.The reference intervals of female PgⅡwere:2.87-23.93μg/L,3.41-33.31μg/L and 3.88-39.16μg/L,respectively.The reference intervals of of female PGⅠ/PGⅡ are 6.6-28.1,5.2-27.9 and 3.6-26.2.Conclusion This study determined the reference range of serum PGs deficiency in healthy subjects of different sex and age in Zhejiang Province.

To explore the role of forkhead box protein O1 (FOXO1) in the progression of glioblastoma multiforme (GBM) and related drug resistance, we deciphered the roles of FOXO1 and miR-506 in proliferation, apoptosis, migration, invasion, autophagy, and temozolomide (TMZ) sensitivity in the U251 cell line using in vitro and in vivo experiments. Cell viability was tested by a cell counting kit-8 (CCK8) kit; migration and invasion were checked by the scratching assay; apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. The construction of plasmids and dual-luciferase reporter experiment were carried out to find the interaction site between FOXO1 and miR-506. Immunohistochemistry was done to check the protein level in tumors after the in vivo experiment. We found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes GBM chemosensitivity to TMZ, which was mediated by autophagy. FOXO1 upregulates miR-506 by binding to its promoter to enhance transcriptional activation. MiR-506 could downregulate E26 transformation-specific 1 (ETS1) expression by targeting its 3'-untranslated region (UTR). Interestingly, ETS1 promoted FOXO1 translocation from the nucleus to the cytosol and further suppressed the FOXO1-miR-506 axis in GBM cells. Consistently, both miR-506 inhibition and ETS1 overexpression could rescue FOXO1 overactivation-mediated TMZ chemosensitivity in mouse models. Our study demonstrated a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in GBM in regulating invasiveness and chemosensitivity. Thus, the above axis might be a promising therapeutic target for GBM.
Animals ; Mice ; Brain Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Feedback ; Gene Expression Regulation, Neoplastic ; Glioblastoma/metabolism* ; MicroRNAs/metabolism* ; Temozolomide/therapeutic use* ; Humans ; Forkhead Box Protein O1/metabolism*

Objective    To investigate the surgical strategies and clinical efficacy of transmitral septal myectomy in the treatment of recurrent left ventricular outflow tract obstruction (LVOTO) after alcohol septal ablation. Methods    The clinical data of patients with recurrent LVOTO after alcohol septal ablation from July 2020 to July 2021 in the Department of Cardiac Surgery, Guangdong Provincial People's Hospital were retrospectively analyzed. Patients were preoperatively evaluated by echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography, 3D modeling and printing technology. A personalized surgical strategy was preoperatively developed according to multimodality imaging assessment, while visual exploration was performed on the digital model and simulated surgical resection was performed on the printed model. Results     Two female patients were enrolled, aged 62 years and 64 years, respectively. Totally endoscopic transmitral extended myectomy was successfully performed on both patients with aortic cross-clamping time of 96 min and 85 min, respectively. LVOTO was relieved immediately (subaortic peak pressure gradient decreased from 100 mm Hg to 4 mm Hg and from 84 mm Hg to 6 mm Hg, respectively) and the mitral regurgitation significantly improved after the procedure. No patient had complete atrioventricular block or required permanent pacemaker implantation. The patients were discharged uneventfully without postoperative complications. Conclusion    Personalized totally endoscopic transmitral extended myectomy combined with multimodality imaging assessment and 3D modeling and printing has an acceptable clinical effect in patients with recurrent LVOTO after alcohol septal ablation. The procedure can precisely resect the hypertrophic septal myocardium while avoiding serious complications such as septal perforation or complete atrioventricular block.

Traumatic intracranial hematoma progresses rapidly and may cause quick increase of intracranial pressure and even brain hernia, ultimately leading to coma or death. Therefore, traumatic intracranial hematoma needs prompt treatment, but the prerequisite of treatment is early examination and diagnosis. Due to the limited transportation and other reasons, the existing large-scale detection devices such as CT and MRI cannot be deployed on the rescue site or during patient transportation. Instead, the portable diagnosis devices have the characteristics of miniaturization and high flexibility, which is conducive to promoting early detection, assisting diagnosis and further guiding the formulation of treatment plans. At present, more and more attention has been paid to the portable diagnosis devices in the diagnosis of intracranial hematoma. The authors summarized the conventional diagnosis methods and application of portable diagnosis devices for traumatic intracranial hematoma, aiming to provide a reference for the diagnosis of traumatic intracranial hematoma.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

The cross regional loose medical alliance is an important carrier in the current integrated development process of medical services in the Yangtze River Delta region. Smith policy implementation process model was used to analyze the development difficulties of cross regional loose medical alliances from idealized policies, policy implementation institutions, policy target groups, and policy implementation environment. Such medical alliances were formed under the background of integrated development in the Yangtze River Delta, with Shanghai′s tertiary public hospitals as leading units and medical institutions in Jiangsu, Zhejiang, and Anhui provinces as member units. Analysis showed that the policies for such medical alliances development had not yet clearly defined the organizational management mode, operational mechanism, and implementation path, and the corporate governance structure of medical alliance was immature; The policy implementation agencies were relatively lagging behind in the support of special funds and the formulation of related supporting policies; Participation of policy target groups was insufficient and their incentive mechanisms was imperfect; There were problems in the policy implementation environment, namely inconsistent medical and health service regulations and systems in different regions, different health financing capabilities of local governments, insufficient coordination of medical institution management concepts, and a lack of unified standards in information systems. Based on the above difficulties, this study proposed to strengthen the development planning and layout of cross regional loose medical alliances, and improve the corporate governance structure; To strengthen the government′s main responsibility and improving policy implementation capabilities; To improve the internal cooperation and operation mechanism of cross regional loose medical alliances, and enhance the sense of identity of the target group; To optimize the policy implementation environment and implement various support measures, so as to provide references for further promoting the coordinated development of high-quality medical resources in the Yangtze River Delta region.

OBJECTIVE: To analyze the phenotype and genetic variant in a pedigree affected with inherited protein C (PC) deficiency. METHODS: The proband and her family members (7 individuals from 3 generations) were tested for plasma protein C activity (PC:A), protein C antigen (PC:Ag) content and other coagulation indicators. All of the 9 exons and flanking sequences of the proband's PROC gene were amplified by PCR and sequenced. Suspected variants were verified by reverse sequencing of the proband and her family members. Bioinformatic software was used to analyze the pathogenicity and conservation of the variant site. Swiss-PdbViewer was used to analyze the three-dimensional model and the interaction with the mutant amino acid. RESULTS: The PC:A and PC:Ag of the proband, her grandmother, father and elder brother were decreased to 55%, 52%, 48%, 51% and 53%, 55%, 50%, 56%, respectively. Genetic analysis showed that the four individuals have all carried heterozygous c.1318C>T (p.Arg398Cys) missense mutation in exon 9 of the PROC gene. The score of MutationTaster was 0.991, PROVEAN was -3.72, and FATHMM was -2.49, all predicted it to be a harmful mutation. Phylogenetic analysis also showed that Arg398 was weakly conservative among homologous species. Protein model analysis showed that, in the wild type, Arg398 can form a hydrogen bond with Glu341 and Lys395 respectively, when it was mutated to Cys398, the hydrogen bond with Glu341 disappears and an additional hydrogen bond was formed with Lys395, which has changed the spatial structure of the protein. CONCLUSION The heterozygous missense mutation c.1318C>T (p.Arg398Cys) of the PROC gene probably underlay the decreased PC:A and PC:Ag in this pedigree.
Aged ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Phylogeny ; Protein C Deficiency/genetics*

Objective:To investigate the relationship between radiation mode and radiation-induced taste cell injury in mouse models.Methods:The head and neck of adult C57/bl mice were exposed to 8 Gy irradiation for 1, 2 and 3 times and sacrificed at 2, 4, 7 and 14 d after irradiation. Frozen sections of taste papilla tissues were treated with specific markers by immunohistochemical staining. The changes of proliferative cells and the number of type Ⅱtaste cells at different time points under different radiation modes were observed. The effect of different radiation dose patterns upon the taste cells was assessed.Results:The count of proliferative cells was decreased significantly on the 2 nd day after radiation, and rapidly recovered to normal level on the 4 th day after radiation, which was not correlated with the dose mode. The number of type Ⅱ taste cells was decreased on the 2 nd day of the first 8 Gy radiation, decreased to the lowest on the 4 th day of the second and third 8 Gy radiation, and rose slowly on the 7 th day. Conclusions:Radiation can initially decrease and subsequently increase the number of proliferative cells to normal range. Besides, it can gradually repair the type Ⅱ taste cell injury. After high-dose irradiation, the decrease of progenitor cells with proliferative function leads to a synchronous decrease in the number of taste function cells, which may be the reason why taste dysfunction cannot be recovered for a long time after radiotherapy.