Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is challenging.There is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor control.However,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint blockade.Using single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in TIL-Bs.HNSCC samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised clustering.This classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to immunotherapy.We found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC patients.Overall,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.

Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.

The p21 activated kinase 4 (PAK4) is serine/threonine protein kinase that is critical for cancer progression. Guided by X-ray crystallography and structure-based optimization, we report a novel subseries of C-3-substituted 6-ethynyl-1H-indole derivatives that display high potential and specificity towards group II PAKs. Among these inhibitors, compound 55 exhibited excellent inhibitory activity and kinase selectivity, displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line B16. Compound 55 exhibited potent in vivo antitumor metastatic efficacy, with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models, respectively. Further mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition (EMT).

Methyltransferase like 13 (METTL13), a kind of methyltransferase, is implicated in protein binding and synthesis. The upregulation of METTL13 has been reported in a variety of tumors. However, little was known about its potential function in head and neck squamous cell carcinoma (HNSCC) so far. In this study, we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level. Increased METTL13 was negatively associated with clinical prognosis. And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro. Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail, the key transcription factor in EMT, hence regulating the progression of EMT. Furthermore, Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes. Altogether, our study had revealed the oncogenic role of METTL13 in HNSCC, and provided a potential therapeutic strategy.
Head and Neck Neoplasms ; Humans ; Squamous Cell Carcinoma of Head and Neck/genetics*

Objective:To investigate the value of rate-pressure product (RPP) in predicating the prognosis of postural tachycardia syndrome (POTS) in children.Methods:Fifty-three children (26 males and 27 females) aged 5 to 15 who had syncope of unknown reasons or presyncope and were diagnosed with POTS by head-up tilt test (HUTT) at the Children′s Syncope Specialist Clinic, the Second Xiangya Hospital, Central South University from April 2012 to May 2019 were selected as the POTS group.Thirty-eight children aged 5 to 16 (19 males and 19 females) who underwent medical examinations at the Children′s Health Specialist Clinic of the Second Xiangya Hospital, Central South University over the same period were enrolled as controls (control group). POTS children were followed up after intervention and they were divided into the response group ( n=40) and the non-response group ( n=13) according to the follow-up results.The products (RPP0, RPP5, RPP10) of the heart rate (HR0, HR5, HR10) and systolic blood pressure (SBP0, SBP5, SBP10) at baseline (HUTT 0 min), HUTT 5 min and HUTT 10 min were calculated.Statistical analysis was performed using SPSS 22.0 software and EmpowerStats software. Results:(1) There was no statistical difference in age and gender between the POTS group and the control group (all P> 0.05). (2) HR5 [(115.45±14.50) times/min vs.(95.79±13.89) times/min], HR10 [(120.57±16.13) times/min vs.(96.05±12.43) times/min], RPP5 (12 814.55±2 304.56 vs.10 371.42±1 910.20), and RPP10 (13 449.17±2 360.40 vs.10 523.18±1 771.48) in the POTS group were significantly higher than those in the control group( t=0.799, 7.842, 5.747, 6.446, all P<0.01). No statistical difference of HR0 and RPP0 was observed between the 2 groups (all P>0.05). (3) In the POTS group: HR5 [(98.73±12.43) times/min vs.(113.77±17.65) times/min], HR10 [(96.90±13.96) times/min vs.(119.08±13.52) times/min], RPP5 (11 125.45±1 952.35 vs.12 914.69±3 192.12) and RPP10 (10 819.58± 2 144.26 vs.13 375.46±2 807.01) in the response group were significantly lower than those in the non-response group( t=3.406, 5.012, 2.432, 3.455, all P<0.01). HR0 and RPP0 were no significantly different between the 2 groups(all P>0.05). (4) When SBP10<114 mmHg(1 mmHg= 0.133 kPa), the probability of response after POTS intervention increased by 10% with every 1 mmHg increase in SBP10, and there was a non-linear relationship between the 2 group ( P<0.05). (5) The receiver operating characteristic curve suggested that when RPP5 was 11 548.50, the sensitivity and specificity to predict the response after POTS intervention were 81.82% and 61.70%, respectively.When RPP10 was 10 988.00, the sensitivity and specificity were 77.78% and 86.21%, respectively. Conclusions:RPP is closely related to the intervention effect of POTS in children.RPP5 and RPP10 can predict the prognosis of POTS in children.There is a non-linear relationship between SBP10 and the intervention effect of POTS in children.

Objective:To analyze the value of shear wave velocity (SWV) combined with thyroid stimulating hormone (TSH) in the diagnosis of hyperthyroidism.Methods:Thirty-five patients with hyperthyroidism who were treated and confirmed in the Fuyang Affiliated Hospital of Anhui Medical University from December 2017 to September 2019 were selected as hyperthyroidism group, and 30 cases of normal health check-up patients in the outpatient department were selected as control group. All of the patients and medical persons were checked by conventional two-dimensional ultrasound and SWV, and the SWV and serum TSH, thyrotrophin receptor antibody(TRAb), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) expression levels of two groups were tested and compared. The correlation relationship in SWV value and serum TSH, TRAb, TGAb, TPOAb levels of hyperthyroidism patients was analyzed by Pearson methods. The receiver operating characteristic curve (ROC curve) method was used to analyze the value of SWV, serum TSH and SWV combined with serum in diagnosis of hyperthyroidism.Results:The SWV values of upper pole, middle pole and lower pole in the hyperthyroidism group had no significant differences ( P>0.05). The SWV values of upper hole, middle pole and lower pole of the left and right lobe of thyroid in the hyperthyroidism group were significantly higher than those in the control group [left lobe: (2.41 ± 0.34) m/s vs. (2.07 ± 0.28) m/s, (2.44 ± 0.39) m/s vs. (2.08 ± 0.25) m/s, (2.46 ± 0.43) m/s vs. (2.04 ± 0.30) m/s; right lobe: (2.47 ± 0.42) m/s vs.(2.01 ± 0.25) m/s, (2.41 ± 0.40) m/s vs. (1.95 ± 0.23) m/s, (2.43 ± 0.35) m/s vs. (2.06 ± 0.24) m/s] ( P<0.01). The serum TSH level in the hyperthyroidism group were significantly lower than that in the control group [(0.05 ± 0.03) kU/L vs. (2.74 ± 1.17) kU/L], while serum TRAb, TGAb and TPOAb levels were significantly higher than those in the control group [(15.82 ± 5.54) U/L vs. (0.55 ± 0.13) U/L, (290.63 ± 145.03) kU/L vs. (25.63 ± 7.12) kU/L, (627.17 ± 250.33) kU/L vs. (34.32 ± 5.95) kU/L], and the differences were statistically significant ( P<0.01). In the hyperthyroidism group, the SWV was negatively correlated with serum TSH ( r=- 0.862, P<0.05), but positively correlated with serum TRAb, TGAb and TPOAb ( r=0.763, 0.837, 0.804, P<0.05). The area under curve(AUC), sensitivity and specificity of combined diagnosis of hyperthyroidism with SWV value and serum TSH were 0.936, 94.29% and 91.43%, which was better than that of SWV (0.803, 80.00%, 74.29%) and serum TSH (0.842, 82.86%, 77.14%). Conclusions:SWV combined with TSH has a high clinical value in the diagnosis of hyperthyroidism.

Jishou University School of Medicine has actively explored the application and effect of online teaching of "ideological and political education" in nursing courses under the COVID-19 epidemic. Taking 135 undergraduates majoring in nursing in batch 2017 as research objects, this study introduces the implementation scheme of online teaching of "ideological and political education". The results show that the online teaching of "ideological and political education" can help nursing undergraduates to establish the professional identity and cultivate medical ethics during the epidemic, to enhance the awareness of the prevention and control of the epidemic, to strengthen the understanding of relevant nursing professional knowledge, and improve students' learning attitude, worthy of reference and promotion.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

OBJECTIVE: To optimize the condition for chromosome flaking of mesenchymal stem cells to ensure the cytogenetic quality control of expanding production and clinical application. METHODS: Chromosomal flaking methods were optimized from current chromosome preparation techniques from the aspects of MSCs cell culture concentration, colchicine treatment time and low permeability time. RESULTS: By repeated pre-experiments, the optimal MSCS chromosome flaking condition of MSCs was determined as cell culture concentration of (1-2)× 10 cells per T25 cell culture bottle, and the colchicines processing time was determined as 2 hours and 10 minutes, and the low permeability was 1 hour. CONCLUSION The optimized chromosome flaking condition can fulfill the requirement of cytogenetic quality control for MSCs.
Cell Culture Techniques ; Cell Differentiation ; Cells, Cultured ; Chromosome Disorders ; Chromosomes, Human ; Cytogenetics ; Humans ; Mesenchymal Stem Cells