1.Research progress of nano drug delivery system based on metal-polyphenol network for the diagnosis and treatment of inflammatory diseases
Meng-jie ZHAO ; Xia-li ZHU ; Yi-jing LI ; Zi-ang WANG ; Yun-long ZHAO ; Gao-jian WEI ; Yu CHEN ; Sheng-nan HUANG
Acta Pharmaceutica Sinica 2025;60(2):323-336
Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.
2.Effect and Mechanism of Menispermi Rhizoma Total Alkaloids on Antiviral Infection
Xuejiao WANG ; Qiqi LI ; Yanli YU ; Xia LIU ; Min LI ; Zhe LIU ; Xin JIA ; Yao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):37-44
ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon (IFN-Ⅰ) signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus (H1N1), vesicular stomatitis virus (VSV), and cerebral myocarditis virus (EMCV) were detected by fluorescent inverted microscope, flow cytometry, Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and Western blot. A mouse model infected with H1N1 was constructed, and the mice were divided into a control group, H1N1 model group, Menispermi Rhizoma total alkaloids groups (10, 20, 30 mg·kg-1), and oseltamivir group (40 mg·kg-1), so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells, and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells (IFNAR1-/--A549) and IFN-Ⅰ pathway was detected. ResultCompared with the control group, the virus proliferated significantly in the model group (P<0.01). Compared with the model group, Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1, VSV, and EMCV in vitro (P<0.01), inhibit the weight loss of the mice infected with the H1N1 in vivo, and improve the survival rate of mice (P<0.05). In addition, Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.
3.Study on policy texts in the field of medical insurance payment system in China from the perspective of policy tools
Wen-Yi ZHENG ; Qing-Wen DENG ; Yu XIA ; Liu LIU ; Ying-Yao CHEN ; Yi YANG
Chinese Journal of Health Policy 2024;17(1):30-35
Objective:To analyze the release and distribution characteristics of Chinese medical insurance payment policies,and to provide reference for future policy formulation in the field of medical insurance payment construction.Methods: Content analysis method was used to construct a two-dimensional framework of "policy goals-policy tools",and text analysis was carried out according to 63 policy documents.Results: A total of 493 policy codes were completed.From the perspective of policy goals,the policy objectives of Chinese medical insurance payment mainly focused on three aspects: improving the payment level,optimizing the medical insurance environment,and standardizing the supervision regulations.From the perspective of policy tools,environmental policy tools are the most used policy tools,followed by supply and demand tools.There is a shortage of financial input and talent training in all policy objectives,so more attention should be paid to demonstration and Category of payment.Conclusion: Our country puts forth effort to build a perfect medical insurance payment system,but should further strengthen policy content supplement,optimize the structure of policy tools,and give full play to the payment ability of medical insurance when pulling the demand of medical insurance payment and driving the supply of medical insurance payment.
4.Establishment of SHERLOCK-HBA Detection Method and Its Application in Blood Identification
Qian-Wei YAO ; Hong-Xia HE ; Sheng HU ; Yi-Xia ZHAO ; Yu LUO ; An-Quan JI ; Qi-Fan SUN
Progress in Biochemistry and Biophysics 2024;51(8):1971-1982
ObjectiveRapid and accurate identification of body fluid traces at crime scenes is crucial for case investigation. Leveraging the speed and sensitivity of nucleic acid detection technology based on SHERLOCK, our research focuses on developing a peripheral blood SHERLOCK-HBA detection system to detect mRNA in forensic practice. MethodsShort crRNA fragments targeting the blood-specific mRNA gene HBA were designed and screened, alongside RPA primers. Optimal RPA primers were selected based on specificity and amplification efficiency, leading to the establishment of the RPA system. The most efficient crRNA was chosen based on relative fluorescence units (RFU) generated by the Cas protein reaction, and the Cas protein reaction system was constructed to establish the SHERLOCK-HBA detection method. The RPA and Cas protein reaction systems in the SHERLOCK detection system were then individually optimized. A total of 79 samples of five body fluids were tested to evaluate the method’s ability to identify blood, with further verification through species-specific tests, sensitivity tests, mixed spots detection, aged samples, UV-irradiated samples, and actual casework samples. ResultsThe SHERLOCK reaction system for the peripheral blood-specific marker HBA was successfully established and optimized, enabling detection within 30 min. The method demonstrated a detection limit of 0.001 ng total RNA, better than FOB strip method and comparable to RT-PCR capillary electrophoresis. The system could detect target body fluids in mixed samples and identify blood in samples stored at room temperature for three years and exposed to UV radiation for 32 h. Detection of 11 casework samples showed performance comparable to RT-PCR capillary electrophoresis. ConclusionThis study presents a CRISPR/Cas-based SHERLOCK-HBA detection system capable of accurately, sensitively, and rapidly identifying blood samples. Introducing CRISPR/Cas technology to forensic body fluid identification represents a significant advancement in applying cutting-edge molecular biology techniques to forensic science.The method’s simplicity, shorter detection time, and independence from specialized equipment make it promising for rapid blood sample identification in forensic cases.
5.Research progress of nanomedical drug delivery system based on aerobic glycolytic regulation for tumor therapy
Yi-jing LI ; Sheng-nan HUANG ; Zi-ang WANG ; Wei-wei ZHI ; Xia-li ZHU
Acta Pharmaceutica Sinica 2024;59(9):2509-2518
Tumor is one of the serious problems threatening human health. There are some limitations in the delivery of commonly used tumor therapy technologies, and the therapeutic effect is not satisfactory, so new anti-tumor strategies need to be developed. The process of tumor cells using glycolysis to produce energy under aerobic conditions is called aerobic glycolysis, which is closely related to tumor growth, proliferation and metastasis, and can provide a new target spot for tumor treatment. Nano drug delivery system has been widely used in targeted tumor therapy because of its advantages of targeted drug delivery, improved anti-tumor efficacy and reduced toxic side effects. Numerous studies have shown that more and more nano drug delivery systems regulates aerobic glycolytic metabolism by targeting to potential targets such as signaling factors or reaction products of aerobic glycolytic process in tumors, and therefore enhance the anti-tumor effect. This paper reviews the application of nano drug delivery system in regulating tumor aerobic glycolysis, and provides theoretical references for realizing efficient targeted tumor therapy.
6.Inhibitory effects of infigratinib and its pharmacologically active metabolites on CYPs and UGTs in rat liver microsomes
Shi-Yu ZHAO ; Shuai-Bing LIU ; Xia YAO ; Xin TIAN
The Chinese Journal of Clinical Pharmacology 2024;40(16):2368-2372
Objective To evaluate the inhibitory effects of infigratinib and its pharmacologically active metabolites,BHS697 and CQM157,on cytochrome P450(CYPs)and UDP-glucuronosyltransferases(UGTs)in rat liver microsomes.Methods By adopting in vitro incubation method,the tested compounds(infigratinib,BHS697 or CQM157)and rat liver microsomes were incubated with the specific probe substrates of CYP2B6,CYP2C8,CYP2C9,CYP2C19,CYP2D6,CYP3 A4,respectively,or the specific probe substrates of UGT1A1,UGT1A3,UGT1A6,UGT1A9,UGT2B7,respectively.The production of characteristic metabolites was detected by high performance liquid chromatography-tandem mass spectrometry.The half maximal inhibitory concentration(IC50)and inhibition constant(Ki)were calculated by GraphPad Prism 8.0.Results Infigratinib,BHS697 and CQM157 weakly inhibited CYP2B6,CYP2C8,CYP2C9,CYP2C19,CYP2D6,CYP3 A4 and UGT1A6,UGT2B7 in rat liver microsomes,with IC50 values all more than 10 μmol·L-1,and moderately inhibited UGT1Al with IC50 values of 2.70,3.17,7.43 μmol·L-,respectively.Infigratinib had a moderate inhibitory effect on UGT1A9 and CQM157 had a moderate inhibitory effect on UGTIA3,with IC50 values of 5.61 and 9.57 μmol·L-1,respectively.The reversible inhibition analysis showed that infigratinib,BHS697 and CQM157 all non-competitively inhibited UGTIA1,with Ki values of 1.83,2.51 and 5.84 μmol·L-1,respectively.Conclusion Infigratinib had moderate inhibitory effects on UGT1A1 and UGT1A9 in rat liver microsomes and its pharmacologically active metabolites,BHS697 and CQM157,also had moderate inhibitory effects on UGT1A1.
7.Advances of CRISPR/Cas-based Biosensor in Detection of Food-Borne Pathogens
Xiao-Yuan ZHANG ; Zhi-Hao YAO ; Kai-Yu HE ; Hong-Mei WANG ; Xia-Hong XU ; Zu-Fang WU ; Liu WANG
Chinese Journal of Analytical Chemistry 2024;52(4):469-480
Rapid and accurate detection methods for food-borne pathogens are essential to ensure food safety and human health.One promising innovation in this area is the clustered regularly interspaced short palindromic repeats/CRISPR-associated systems(CRISPR/Cas)biosensor,which utilizes Cas protein and CRISPR RNA(crRNA)ribonucleo protein to specifically recognize target genes,and converts target signals into detectable physical and chemical signals.The CRISPR/Cas biosensor shows many advantages,such as high specificity,programmability,and ease of use,making it promising to pathogen detection.This paper introduced the principles and characteristics of CRISPR/Cas systems,along with the strategies for signal recognition,amplification,and output based on different CRISPR/Cas biosensors,and their respective applications in food-borne pathogen detection.Furthermore,the construction principles and challenges of multiple biosensors based on CRISPR/Cas were explored,as well as their potential for simultaneous detection of multiple pathogens.Finally,the challenges and future development trends of CRISPR/Cas-based biosensors in rapid pathogen detection were discussed,aiming to provide valuable reference and inspiration for biosensor designers and food safety practitioners.
8.Research Progress of Biomimetic Imprinting Affinity Analysis Technique
Zhao-Zhou LI ; Yu-Hua WEI ; Xiao-Chong ZHANG ; Xiu-Jin CHEN ; Yao WANG ; Hua-Wei NIU ; Fang LI ; Hong-Li GAO ; Hui-Chun YU ; Yun-Xia YUAN
Chinese Journal of Analytical Chemistry 2024;52(6):763-777
Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.
9.Outcome of bariatric surgery in patients with unexpected liver cirrhosis:A multicenter study from China
Sun XIA ; Yao LIBIN ; Kang XING ; Yu WEIHUA ; Kitaghenda Kakule FIDELE ; Mohammad Sajjad Ibn Rashid ; Taguemkam Nogue ANGELINE ; Hong JIAN ; Dong ZHIYONG ; Sun XITAI ; Zhu XIAOCHENG
Liver Research 2024;8(3):172-178
Background and aims:Liver cirrhosis is a complex disease that may result in increased morbidity and mortality following bariatric surgery(BS).This study aimed to explore the outcome of BS in patients with unexpected cirrhosis,focusing on postoperative complications and the progression of liver disease. Methods:A retrospective study of bariatric patients with cirrhosis from four centers in China between 2016 and 2023 was conducted,with follow-up for one year after BS.The primary outcome was the safety of BS in patients with unexpected cirrhosis,while the secondary outcome was the metabolic efficacy of BS in this group postoperatively. Results:A total of 47 patients met the study criteria,including 46 cases of Child-Pugh class A cirrhosis and 1 case of Child-Pugh B.Pathological examination confirmed nodular cirrhosis in 21 patients(44.68%),pseudolobule formation in 1 patient(2.13%),lipedema degeneration with inflammatory cell infiltration in 3 patients(6.38%),and chronic hepatitis in 1 patient(2.13%).The average percentage of total weight loss was 29.73±6.53%at one year postoperatively.During the 30-day postoperative period,the complication rate was 6.38%,which included portal vein thrombosis,gastrointestinal bleeding,and intra-abdominal infection.Moreover,no cases of liver decompensation or mortality were reported during the follow-up period.The remission rates of comorbidities among 41 patients one year after surgery were as fol-lows:dyslipidemia 100%,type 2 diabetes 82.61%,hypertension 84.62%,and obstructive sleep apnea syndrome 85.71%. Conclusions:BS can be safely performed in patients with unexpected cirrhosis in the compensated stage of liver disease,with low postoperative morbidity and no mortality observed during one-year follow-up.
10.Immune Reconstitution after BTKi Treatment in Chronic Lymphocytic Leukemia
Yuan-Li WANG ; Pei-Xia TANG ; Kai-Li CHEN ; Guang-Yao GUO ; Jin-Lan LONG ; Yang-Qing ZOU ; Hong-Yu LIANG ; Zhen-Shu XU
Journal of Experimental Hematology 2024;32(1):1-5
Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4%)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P<0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P<0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P<0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P<0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P>0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P<0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P<0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

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