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Oleanolic acid (OA), a ubiquitous pentacyclic oleanane-type triterpene isolated from edible and medicinal plants, exhibits a wide spectrum of pharmacological activities and tremendous therapeutic potential. However, the undesirable pharmacokinetic properties limit its application and development. Numerous researches on structural modifications of OA have been carried out to overcome this limitation and improve its pharmacokinetic and therapeutic properties. This review aims to compile and summarize the recent progresses in the medicinal chemistry of OA derivatives, especially on structure-activity relationship in the last few years (2010-2021). It gives insights into the rational design of bioactive derivatives from OA scaffold as promising therapeutic agents.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies with poor prognosis. There is no research about the clinical significance of serum soluble CD155 (sCD155) level for HCC. We aim to explore the prognostic and diagnostic value of sCD155 in HCC patients undergoing curative resection.Serum sCD155 level in HCC patients was determined by enzyme-linked immunosorbent assay. The prognostic significance of sCD155 was evaluated by Cox regression and Kaplan-Meier analyses. CD155 expression and biomarkers of immune cells in HCC tissues were detected by immunohistochemistry staining. The diagnostic significance of sCD155 was evaluated using receiver operating characteristic curve.Serum sCD155 level was significantly increased in HCC patients and predicted poor prognosis. The prognostic value of sCD155 remained in low recurrent risk subgroups of HCC. Serum sCD155 level was positively related to CD155 expression in HCC tissues. High serum sCD155 level was associated with decreased numbers of CD8Serum sCD155 level represents a promising biomarker for diagnosis and prognosis of HCC. High serum sCD155 level may reflect an immunosuppressive tumor microenvironment in HCC.

An optimal risk-scoring system enables more targeted offers for colonoscopy in colorectal cancer (CRC) screening. This analysis aims to develop and validate scoring systems using parametric and non-parametric methods for average-risk populations.Screening data of 807,695 subjects and 2806 detected cases in the first-round CRC screening program in Shanghai were used to develop risk-predictive models and scoring systems using logistic-regression (LR) and artificial-neural-network (ANN) methods. Performance of established scoring systems was evaluated using area under the receiver operating characteristic curve (AUC), calibration, sensitivity, specificity, number of high-risk individuals and potential detection rates of CRC.Age, sex, CRC in first-degree relatives, chronic diarrhoea, mucus or bloody stool, history of any cancer and faecal-immunochemical-test (FIT) results were identified as predictors for the presence of CRC. The AUC of LR-based system was 0.642 when using risk factors only in derivation set, and increased to 0.774 by further incorporating one-sample FIT results, and to 0.808 by including two-sample FIT results, while those for ANN-based systems were 0.639, 0.763 and 0.805, respectively. Better calibrations were observed for the LR-based systems than the ANN-based ones. Compared with the currently used initial tests, parallel use of FIT with LR-based systems resulted in improved specificities, less demands for colonoscopy and higher detection rates of CRC, while parallel use of FIT with ANN-based systems had higher sensitivities; incorporating FIT in the scoring systems further increased specificities, decreased colonoscopy demands and improved detection rates of CRC.Our results indicate the potentials of LR-based scoring systems incorporating one- or two-sample FIT results for CRC mass screening. External validation is warranted for scaling-up implementation in the Chinese population.

Colorectal cancer (CRC) is the third most common cancer in men and the second most common cancer in women worldwide. CRC is the second leading cause of cancer-related deaths. Although some progress in the treatment of CRC has been achieved, the molecular mechanism of CRC is still unclear. In this study, alcohol dehydrogenase 1C(ADH1C) was first identified as a target gene closely associated with the development of CRC by the comprehensive application of transcriptomics, proteomics, metabonomics and in silico analysis. The ADH1C mRNA and protein expression in CRC cell lines and tumor tissues was lower than that in normal intestinal epithelial cell lines and healthy tissues. Overexpression of ADH1C inhibited the growth, migration, invasion and colony formation of CRC cell lines and prevented the growth of xenograft tumors in nude mice. The inhibitory effects of ADH1C on CRC cells in vitro were exerted by reducing the expression of PHGDH/PSAT1 and the serine level. This inhibition could be partially reversed by adding serine to the culture medium. These results showed that ADH1C is a potential drug target in CRC.

The present paper was aimed to study the role of spleen tyrosine kinase (Syk) in angiogenesis in hepatopulmonary syndrome (HPS) and the underlying mechanism. Sprague Dawley (SD) rats were randomly divided into three groups: sham operation group (sham group), common bile duct ligation (CBDL) 5-week group (5W group) and R788 intervention group (R788 group). HPS model was established by CBDL. Rats in R788 group were intraperitoneally injected with R788 (20 mg/kg) once daily to week 5 after CBDL operation. The protein expression levels and distribution of Syk, p-Erk1/2, and p-Akt in lung tissue were detected by Western blot and immunohistochemistry. Immunofluorescence staining was used to observe the location of Syk expression and the number of angiogenesis in lung tissue. The results showed that, compared with sham group, 5W group exhibited up-regulated protein expression level of Syk, increased phosphorylation levels of Erk1/2 and Akt, and increased number of pulmonary microvessels. Compared with 5W group, R788 group exhibited down-regulated protein expression level of Syk, decreased phosphorylation levels of Erk1/2 and Akt, and decreased number of pulmonary microvessels. These results suggest that Syk may promote pulmonary angiogenesis in HPS model rats by activating downstream Erk1/2 and Akt signaling pathways, which provides a theoretical basis and potential drug therapeutic targets for the clinical treatment of HPS.

Traditional Chinese medicine (TCM) is regarded as a large database containing hundreds to thousands of chemical constituents that can be further developed as clinical drugs, such as artemisinin in Artemisia annua. However, effectively exploring novel candidates is still a challenge faced by researchers.In this work, an integrated strategy combining chemical profiling, molecular networking, chemical isolation, and activity evaluation (CMCA strategy) was proposed and applied to systematically characterize and screen novel candidates, and Forsythiae fructus (FF) was used as an example.It contained four parts. First, the chemical compounds in FF were detected by ultra-high-performance liquid chromatography-mass spectrometry (UPLC/Q-TOF MS) with data-dependent acquisition, and further, the targeted compounds were screened out based on an in-house database. In the meantime, the representative MS/MS fragmentation behaviors of different chemical structure types were summarized. Second, homologous constituents were grouped and organized based on feature-guided molecular networking, and the nontargeted components with homologous mass fragmentation behaviors were characterized. Third, the novel compounds were isolated and unambiguously identified by nuclear magnetic resonance (NMR). Finally, the anti-angiotensin-converting enzyme 2 (ACE2) activities of isolated chemical constituents were further evaluated by in vitro experiments.A total of 278 compounds were profiled in FF, including 151 targeted compounds and 127 nontargeted compounds. Among them, 16 were unambitiously identified by comparison with reference standards. Moreover, 25 were classified into potential novel compounds. Two novel compounds were unambiguously identified by using conventional chromatographic methods, and they were named phillyrigeninside D (peak 254) and forsythenside O (peak 155). Furthermore, the ACE2 activity of the compounds in FF was evaluated by modern pharmacological methods, and among them, suspensaside A was confirmed to present obvious anti-ACE2 activity.Our work provides meaningful information for revealing potential FF candidates for the treatment of COVID-19, along with new insight for exploring novel candidates from complex systems.

Four previously undescribed glutamic acid derivatives, verticillamines A-D (1–4), together with six known compounds (5–10) were isolated from the bulbs of Fritillaria verticillate Willd. The structures of (1−10) were established on the basis of UV, IR, MS, 1D and 2D NMR, and the absolute configurations of compounds (1–4) were determined by calculated ECD methods. Among them, compounds (1–3) were rare 2-methyl-γ-lactam alkaloid derivatives. Moreover, both γ-lactam alkaloids (1–5) and pyrrolidine alkaloids (6–7) were discovered in Fritillaria for the first time. Compound 8 exhibited moderate cytotoxic activities against A2780 and HepG 2 cells, with IC50 values of 11.7 ± 5.2 μM and 25.6 ± 2.8 μM.

The aim of this study was to simulate pedestrian movements in the queuing process in subway stations using microscopic simulation models. The queuing process was divided into two stages – walking and selecting a queue, and entering a queue and waiting in that queue. To represent the boundary of these two stages, a novel queuing line concept was developed. This queuing line dynamically changes with factors such as pedestrian preference, queue shape and queue length. Furthermore, two corresponding microscopic simulation models were developed to handle those two stages on the basis of the social force model and the queuing rule, respectively. Typically, the queuing rule is determined by the desired force, the impact of the nearest pedestrian ahead in the same direction and a self-stopping mechanism. Two examples – a ticket office and a security check in a subway station – were used to verify the validity of the proposed models.

Objective To identify risk factors for preoperative respiratory complications associated with tracheobronchial foreign body aspiration (TFBA) by retrospectively analysing paediatric cases presenting with or without complications. Methods Paediatric patients who presented with TFBA and were admitted to hospital were enrolled in the study. Patients were divided into two groups based on occurrence of preoperative respiratory complications as confirmed by computed tomography. Age, sex, TFBA symptoms, type of foreign body, retention timeand location of the foreign body were documented and compared between the groups. Results In total, 223 children were included: group A ( n = 161) included those with respiratory complications; group B ( n = 62) included those without respiratory complications. Univariate and multivariate analyses found that type of foreign body, and symptoms differed significantly between the two groups. Conclusion Respiratory complications of TFBA in children were correlated with the type of foreign body and symptoms.

On the basis of analysis of the named,Introduces the development of teaching process of roll machine, roll machine for teaching digital tube display random results, intuitive and clear, and good use effect.

Ischemic postconditioning (IPO) had been reported as a promising method against myocardial ischemia-reperfusion (I/R) injury, but IPO was later proved with poor clinical benefit. In this study, we compared the protective effects of pinacidil-postconditioning (PPO) and IPO against myocardial I/R injury. Langendorff rat hearts were randomly assigned to one of the following groups (n=8 each): Control group, I/R group (40min ischemia and 60min reperfusion), IPO group (6 successive cycles of 10s reperfusion per 10s occlusion before fully reperfusion), PPO group (perfused with 50μM pinacidil for 5min before reperfusion). Heart performance, infarct size and mitochondrial respiratory function were evaluated, and target genes/proteins of well-known Nuclear Factor-E2 Related Factor 2 (Nrf2) were assessed. Both IPO and PPO preserved heart function and myocardial ultrastructure at the end of reperfusion (all P