Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To explore the the detection of MMP-2,-7,-9,and-12 enzymatic activity using the CEACAM1-derived fluorescent peptide substrate Site 84,investigating the application of substrate Site 84 to distinguishing between MMP-2 and MMP-9 in the gelatinase spectrum of MMPs.Methods The fluorescent enzymatic method was employed to observe the detection of MMP-2,-7,-9,and-12 enzymatic activity using substrate Site 84;further observations were made on the sensitivity and specificity of substrate Site 84 to enzymatic activity of MMP-2 and MMP-9 within the gelatinase spectrum;the kinetic parameters(Km and Kcat)of the enzymatic reaction between substrate Site 84 and MMP-2 were obtained.Results Using Site 84 as a substrate,enzymic kinetics curves for MMP-12,-7,-2 were obtained,but no enzymatic activity curve for MMP-9 was observed.Furthermore,Site 84 specifically detected the enzymatic activity of MMP-2 within the gelatinase spectrum,capable of detecting low concentration(0.6 μM)of MMP-2 enzymatic activity,but no obvious enzymatic reaction was observed for high concentration(6 μM)of MMP-9;the kinetics parameters for the enzymatic reaction between Site 84 and MMP-2 were Km=315 μM,Kcat/Km=2 565/MS.Conclusion The CEACAM1-derived substrate Site 84 serves as a novel fluorescent peptide substrate,enabling the acquisition of enzymatic activity curves for MMP-12,-7 and-2,and specifically detecting the enzymatic activity of MMP-2 within the MMP gelatinase spectrum.

The purpose of this paper is to systematically summarize the gene polymorphisms associated with osteoporosis(OP)susceptibility in Zhuang ethnic group in Guangxi.These genes mainly encode vitamin D receptor,estrogen receptor,calcitonin receptor,and adiponectin.The genotype and allele distribution frequency were compared between Zhuang ethnic group and other ethnic groups,which can clarify the existing genes and the potential gene polymorphism associated with OP in Zhuang ethnic group.The findings provide a representative solution for the subsequent research on the genes associated with OP susceptibility in ethnic minorities.

OBJECTIVES: To develop a Chinese version of the Long-Term Conditions Questionnaire (LTCQ) and to test its reliability and validity in Chinese patients with chronic diseases. METHODS: With the consent of the original authors, a Chinese version of LTCQ was developed according to the cultural adjustment guidelines. A questionnaire survey was conducted on 319 patients with chronic diseases in Sir Run Run Shaw Hospital, Wuyi County First People's Hospital and Hangzhou Gongchen Bridge Street Health Service Center. The questionnaire was evaluated by item analysis (including frequency analysis, total question correlation method and critical ratio method), reliability analysis (Cronbach's alpha coefficient) and validity analysis [including content validity (expert scoring method) and structural validity (exploratory factor analysis)]. RESULTS The Chinese version of the LTCQ included 20 entries, with a Cronbach's alpha coefficient of 0.926, a retest reliability of 0.829, a split-half reliability of 0.878, an entry content validity index of 1, and a content validity index at the questionnaire level of 1. Four common factors were extracted by exploratory factor analysis, namely physical state and daily life, psychological state, support and coping, and safe environment, with a cumulative variance contribution rate of 67.244%. Discussion: The Chinese version of the LTCQ developed in this study has good reliability and validity and it may be used to assess the long-term conditions of patients with chronic diseases in China.
Humans ; Asian People ; China ; Chronic Disease ; Quality of Life ; Reproducibility of Results ; Surveys and Questionnaires

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.
Humans ; Organoids ; Neovascularization, Pathologic ; Technology

Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.

【Objective】 To investigate the effect of exosomes produced by hepatitis B virus (HBV)-infected cells on the phenotype and function of macrophages. 【Methods】 The exosomes secreted by HepAD38 cells, which were capable of producing HBV and HepG2 cells, were collected by ultracentrifugation combined with immunosorbent method.The quality and purity of the extracted exosomes were verified by nanoparticle tracking analysis (NTA), scanning electron microscope and Western blot.The M0 THP-1 macrophages differentiated by PMA were stimulated by HepAD38 derived- or HepG2 derived exosomes.Total RNA and protein samples were collected at different time points after stimulation.Real-time fluorescence quantitative PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect cytokine mRNA and protein expressions, respectively.Meanwhile, neutral red assay was performed to analyze macrophage pinocytosis activity, and a commercial kit was used to measure reactive oxygen species (ROS) in THP-1 macrophages.Human reverse transcription chip detection was performed to obtain the microRNAs profile of the exosomes.And the effect of selected miRNA on macrophages was further confirmed by qRT-PCR. 【Results】 Compared with HepG2-derived exosomes, HepAD38-derived exosomes increased the mRNA and protein expressions of IL-1β, MCP-1 and TNFα significantly.However, no difference of pinocytosis capacity or ROS production was found between the HepAD38-derived exosomes group and HepG2-derived exosomes group.Human reverse transcription chip detection results were verified by KEGG analysis and qRT-PCR, and it was found that miR-6824-3p could also significantly increase the expression levels of IL-1β, MCP-1 and TNFα after high expression. 【Conclusion】 This study found that exosomes produced by HepAD38 cells may stimulate macrophages to produce inflammatory factors such as IL-1β, MCP-1 and TNFα through miR-6824-3p, thereby playing a role in HBV infection.

Objective:To systematically analyze and compare the focuses and frontiers of research on microbial resistance to disinfectants in China and abroad, and to provide suggestions for strengthening academic research on microbial resistance to disinfectants as well as the prevention and control of antimicrobial resistance in China.Methods:Relevant literature focusing on the resistance of microorganisms to disinfectants was retrieved from the China National Knowledge Infrastructure (CNKI) and Web of Science? Core Collection database from January 1, 1994 to December 31, 2018. After analyzing the basic information of the literature, co-occurrence and cluster analyses by the CiteSpace visualization software were introduced to identify and compare the similarities and differences of topics and frontiers between domestic and foreign research on microbial resistance to disinfectants.Results:A total of 234 literatures published in Chinese and 1 563 literatures in English were included. Among the 1 563 literatures in English, 97 literatures were published by domestic scholars as the first author or corresponding author, and 1 466 literatures by foreign scholars. The quality of the journals publishing these studies was relatively high. Compared with the general trend of foreign research in this field, the number of relevant articles published by domestic scholars started to decline in recent years, and the journals were relatively concentrated. According to the co-occurrence analysis on keywords, " Acinetobacter baumannii" had the highest centrality value of 0.36 among the literatures published in Chinese by domestic scholars, while " Escherichia coli" was presented with the highest centrality value of 0.63 and 0.21 in English literatures published by domestic and foreign scholars, respectively. According to the analysis of the research trends of the literatures, much more burst terms were detected in the papers published in English by foreign scholars. Among those literatures published from 1994 to 2018, the focuses on the types of pathogens had gradually shifted from Escherichia coli and Staphylococcus aureus to Klebsiella pneumoniae and Salmonella enterica, and the attention to the types of disinfectants had gradually switched from chlorhexidine and quaternary ammonium compound to sodium hypochlorite and peracetic acid. However, only a few burst terms, mainly including "bacteria" and " Pseudomonas aeruginosa" , were detected in the papers published in Chinese by domestic scholars, which emerged in an earlier period and ended in 2008 and 2010. Conclusion:Although domestic research on microbial resistance to disinfectants has made some progresses and gradually achieved international standard, comprehensive and in-depth research should be consistently strengthened to form a stable and sustainable development pattern.

Objective: To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation. Methods: Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing. Results: Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed. Conclusions This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.

Objective To explore the expressions and significance of brain natriuretic peptide (BNP),hypersensitive C-reactive protein (hs-CRP),human fibrinogen (Fib),D-Dimer and blood gas analysis in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and pulmonary hypertension (PH).Methods Totally 135 patients with AECOPD were divided into single AECOPD group (n =75) and AECOPD + PH group (n =60).The value of pulmonary systolic pressure (PASP) was measured by echocardiography.Serum BNP,hs-CRP,D-Dimer,Fib levels and arterial blood gas analysis indexes such as p(CO2) and p(O2) were compared between two groups.Results The levels of hs-CRP,BNP,D-Dimer and p(CO2) in AECOPD + PH group were significantly higher than those in AECOPD group (P ＜ 0.05),while p (O2) in AECOPD + PH group was significantly lower than that in AECOPD group.Multiple linear regression analysis showed that the levels of hs-CRP,Fib,BNP,D-Dimer and p (CO2) were positively correlated with pulmonary artery pressure (P ＜ O.05),and p (02) was negatively correlated with PASP (P ＜ 0.05).Conclusion The hs-CRP,Fib,BNP,and D-Dimer participate in the formation of AECOPD complicated with pulmonary hypertension,and systemic inflammation plays an important role in the pathogenesis of AECOPD complicated with pulmonary hypertension.