As one of the most prevalent gastrointestinal malignancies in humans,gastric cancer(GC)is often detected at an advanced stage,resulting in a poor prognosis and ranking it the fifth leading cause of cancer-related deat...As one of the most prevalent gastrointestinal malignancies in humans,gastric cancer(GC)is often detected at an advanced stage,resulting in a poor prognosis and ranking it the fifth leading cause of cancer-related deaths.Due to their high genomic correlation with humans,mice are ideal in vivo models for investigating GC-related pathogenesis and therapeutic interventions.This review provides an overview of different GC models,including genetically engineered,transplantation-based models,and chemically or biologically induced models,and discusses the recent advancements for each type,highlighting their unique contributions to the field.In addition,it summarizes the strengths,limitations,and typical applications of these models and offers a critical assessment of their applicability in research while acknowledging their current limitations in fully mirroring human GC progression.Furthermore,we analyze how each model accurately recapitulates the complexities of human GC and evaluate their potential for clinical translation.This review provides a reference for model selection in future GC research.展开更多
Extracellular vesicles(EVs)have emerged as a promising technology for diagnostic and therapeutic applications in clinical settings over the past decade.However,their advancement is hindered by complex technological an...Extracellular vesicles(EVs)have emerged as a promising technology for diagnostic and therapeutic applications in clinical settings over the past decade.However,their advancement is hindered by complex technological and regulatory challenges.This review outlines key considerations in the manufacturing process,quality management,and nonclinical evaluation relevant to EV-based drug development.Furthermore,we summarize and compare technical regulatory requirements across major countries to help clarify the regulatory principles governing EV products.Our analysis reveals an ongoing international debate regarding the regulatory review of EVs.Nevertheless,adopting a risk-based classification framework that categorizes EV products as advanced therapeutic drugs is a rational approach.Critical challenges include the development of standardized production protocols,a clearer understanding of therapeutic mechanisms,and resolving complex regulatory issues.展开更多
Objective: To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therape...Objective: To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therapeutic mechanism. Methods: Ninety repeatedly attacking acute gouty arthritis patients were divided into the treated group ( n =60) and control group ( n =30). The treated group was treated with RBXG, and the control group was treated with Futalin tablets (diclofenac sodium). The baseline treatment including good rest, low purine diet, sufficient water drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine 600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage to establish the animal models. Results: The clinical effective rate of the treated group was 95.0% and that of the control 90.0%. Good therapeutic effects were won, insignificant difference ( P >0.05)was shown between the two groups. However, the cure rate of the treated group was 26.7% while that of the control group was 10.0%, with significant difference ( P <0.01) shown between them. The treated group had its blood uric acid lowered, which was significantly different ( P <0.05) from that of the control group. The animal experiment indicated that all the three groups treated with different dosages of RBXG, as well as the Ash bark and Smilax glabra rhizome groups had their blood uric acid content reduced in the hyperuricemic mice. Conclusion: RBXG has a quicker initiation and better treatment effects than sole anti-inflammatory and analgesic agents on the treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic or adverse reactions and therefore good for long-term administration and likely to be a safe TCM preparation to control the symptoms and reduce the onsets of repeatedly attacking of acute gouty arthritis. The animal experiment shows that both the compound preparation and part of the single ingredients in the recipe have the function of reducing blood uric acid. However, the compound recipe has better therapeutic effects, proving to be superior to single drugs.展开更多
China's participation in global governance,inspired by the 17 United Nations Sustainable Development Goals,is driven by the guiding principle of"Building a Community of Shared Future for Mankind".China h...China's participation in global governance,inspired by the 17 United Nations Sustainable Development Goals,is driven by the guiding principle of"Building a Community of Shared Future for Mankind".China has been promoting the Belt and Road Initiative and South-South Cooperation and has made significant contributions to the prosperity of human beings.Along with the opportunities that globalization brought about such as the World Health Organization and the boom in the economy,global health challenges also emerged.This resulted in certain obstacles for China when it sought to advocate the Belt and Road Initiative and when it attempted to carry out its strategy to address global health issues.What are the emerging challenges for global health?What can China do for global health?Why does global health need China?We tried to address these questions as China's global engagement continues to expand in the new era.This article makes the case for Chinese approaches,including getting involved in public health,being consistent in addressing local conditions,and sharing China's experience with handling health services and staying in the lead through government action while being guided by relative policies.China has a lot to offer in the promotion of global health and in overcoming the challenges and risks that this goal currently faces.Thus,China should be considered an inseparable part of global health governance and bilateral health development cooperation.展开更多
Objective: To study the effect of adding different concentrations of soybean lecithin in Tris based extender and to compare the results of Tris soybean lecithin extender with two commercial diluents (egg yolk-based: B...Objective: To study the effect of adding different concentrations of soybean lecithin in Tris based extender and to compare the results of Tris soybean lecithin extender with two commercial diluents (egg yolk-based: BullXcell and plant-based: OptiXcell) for Damascus goat sperm cryopreservation. Methods: The ejaculates from 4 mature male Damascus goats were obtained by using an artificial vagina. Semen samples were pooled and diluted in Tris extender supplemented with soybean lecithin at different concentrations of 1.5%, 3.0%, 6.0% and 10.0% to get better concentration to be used for further experiments, with a final concentration of 240×106 spermatozoa/mL. Semen samples were packed in straws (0.25 mL), frozen by using an automated system and stored in liquid nitrogen at -196 ℃ for 48 h. After thawing (37 ℃/30 s), the samples were evaluated for sperm quality parameters, including sperm motility, membrane integrity and acrosome integrity. Malondialdehyde concentration was estimated as a marker for lipid peroxidation. Based on the previous investigations, only Tris extender supplemented with 3.0% soybean lecithin (based on its positive results) was used versus BullXcell and OptiXcell for sperm ultrastructure evaluation and artificial insemination by using electron microscope and artificial insemination of the synchronized does. Results: There was no significant difference between Tris-soybean lecithin at 3.0% and BullXcell/OptiXcell diluents in post-thaw sperm parameters and fertility following artificial insemination;meanwhile, the other concentrations of soybean lecithin (1.5%, 6.0% and 10%) showed lower sperm parameters following cryopreservation. Conclusions: Using of Tris-soybean lecithin based extender at the level of 3.0% can be an appropriate alternative to either BullXcell or OptiXcell for Damascus goat sperm cryopreservation.展开更多
This study aimed to evaluate emerging trends of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) among 290 former blood donor HIV-1 inf...This study aimed to evaluate emerging trends of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) among 290 former blood donor HIV-1 infected patients in Hubei, China, from 2004 to 2006, all of whom had received anti-HIV-1 therapy. The presence of NRTI- and NNRTI-associated mutations were established by sequencing; genotypic and predicted phenotypic drug resistance were evaluated using HIVdb Program version 5.0.1 (http://hivdb.stanford.edu/ pages/algs/HIVdb.html). Genotypic drug resistance analysis showed significant increases in percentages of patients carrying HIV-1 strains with M41L, T215Y/F, D67N, K103N, G190A/S, Y181C/F or L210W mutations. Of the variants' predicted phenotypic drug resistance, highly significant increases were detected in percentages of patients carrying HIV-1 with high resistance to zidovudine (AZT) or stavudine (D4T) in NRTIs, and to delavirdine (DLV), efavirenz (EFV) or nevirapine (NVP) in NNRTIs; intermediate resistance to abacavir (ABC), AZT, D4T, didanosine (DDI) or tenofovir disoproxil fumarate (TDF) in NRTIs, and to etravirine (ETR) in NNRTIs; and low and potential low resistance to lamivudine (3TC), ABC, emtricitabine (FTC) or TDF in NRTIs, and to ETR in NNRTIs.展开更多
Acquired bone marrow failure diseases(ABMFD) are a class of hematopoietic stem cell diseases with a commonality of non-inherited disruption of hematopoiesis that results in pancytopenia. ABMFDs also are a group of het...Acquired bone marrow failure diseases(ABMFD) are a class of hematopoietic stem cell diseases with a commonality of non-inherited disruption of hematopoiesis that results in pancytopenia. ABMFDs also are a group of heterogeneous diseases with different etiologies and treatment options. The three most common ABMFDs are aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Stem cell transplantation is the only treatment that can cure these diseases. However, due to high therapy-related mortality, stem cell transplantation has rarely been used as a first line treatment in treating ABMFD. With the advance of personalized medicine and precision medicine, various novel cellular therapy strategies are in trial to increase the efficiency and efficacy of ABMFD treatment. This article aims to review current available stem cell transplantation protocols and promising cellular therapy research in treating ABMFD.展开更多
Objectives: Although the naphthoquinone, 7-methyljuglone (7-MJ), is active against Mycobacterium tuberculosis (MTB) in vitro, neither the cellular site nor mechanism of anti-mycobacterial action of this agent has been...Objectives: Although the naphthoquinone, 7-methyljuglone (7-MJ), is active against Mycobacterium tuberculosis (MTB) in vitro, neither the cellular site nor mechanism of anti-mycobacterial action of this agent has been identified. The primary objective of the current study was to investigate the mycobacterial outer membrane as a potential target of 7-MJ by measuring the effects of this agent (0.023 - 1.5 mg/L) on microbial ATP levels and uptake of K+ . Methods: Bioluminescence and radiometric (uptake of 86Rb+) procedures were used to assay microbial ATP levels and K+ transport respectively. Results: Exposure of MTB (strain H37Rv) to 7-MJ for 60 min resulted in dose-related decreases in both microbial ATP levels and uptake of 86Rb+ which achieved statistical significance (P + transport.展开更多
Objective: to analyze the adverse reactions of DPT vaccination in children, and to explore the relevant preventive countermeasures and application effect. Methods: in January 2020, Lianyun District began to actively i...Objective: to analyze the adverse reactions of DPT vaccination in children, and to explore the relevant preventive countermeasures and application effect. Methods: in January 2020, Lianyun District began to actively implement the preventive intervention measures of adverse reactions to pediatric DPT vaccination, Children who have completed the vaccination of prevention countermeasures in Lianyun District before the implementation of this study (January 1,2017 to December 31,2019) and after the implementation (January 1,2020 to December 31,2021). As the routine guidance group (23,921 doses) and the preventive intervention group (11,383 doses), monitoring the adverse reactions and satisfaction with vaccination care in both groups, analyze the effects of the preventive intervention. Results: the general response (0.31%) and total incidence of adverse reaction (0.31%) were significantly lower than the conventional guidance group (0.18%, 0.18%) (P <0.05), and the incidence of abnormal response between the two groups (P> 0.05). Parent satisfaction with vaccination care in the preventive intervention group (99.90%) was significantly higher than that in the conventional guidance group (92.75%) (P <0.05). Conclusion: there are some risks of adverse reactions after vaccination with DPT vaccine, mainly general reactions, which can reduce the risk of adverse reactions and have high application value, which is worth promotion and reference.展开更多
Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initi...Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.展开更多
Follicular helper T （TFH） cells represent a distinct subset of CD4＋ helper T （TH） cells specialized in providing help to B cells. They are characterized by their unique transcriptional profile （Bcl6）, surface m...Follicular helper T （TFH） cells represent a distinct subset of CD4＋ helper T （TH） cells specialized in providing help to B cells. They are characterized by their unique transcriptional profile （Bcl6）, surface marker expression （CXCR5, PD-1, ICOS and CD4OL） and cytokine production pattern （IL-21 and IL-6）. TFH cells provide help to B cells both to form germinal centers （GCs） and to differentiate into memory B cells and plasma cells for generation of humoral responses. However, there is emerging evidence that implicates TFH cells in the development of various human pathologies, such as autoimmune diseases, immunodeficiency and lymphoma. This review focuses on the current progress in this area including mouse and human studies. A clearer understanding of the mechanisms of TFH cell-mediated immunity and pathology may be exploited for rational development of therapeutic strategies. Cellular＆ Molecular Immunology（2012） 9, 380-385; doi：10.1038/cmi.2012.26; published online 13 August 2012展开更多
Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophag...Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 （PLP2-TM） of coronaviruses acts as a novel autophagy- inducing protein. Intriguingly, PLP2-TM induces incom- plete autophagy process by increasing the accumula- tion of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2- TM interacts with the key autophagy regulators, LC3 and Beclinl, and promotes Beclinl interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclinl partially reverses PLP2-TM＇s inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results sug- gested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclinl, which in turn modulates coronavirus replication and antiviral innate immunity.展开更多
Plant intracellular nucleotide-binding leucine-rich repeat(NLR)receptors with an N-terminal Toll/Interleukin-1 recep-tor(TIR)domain detect pathogen effectors to produce TIR-catalyzed signaling molecules for activation...Plant intracellular nucleotide-binding leucine-rich repeat(NLR)receptors with an N-terminal Toll/Interleukin-1 recep-tor(TIR)domain detect pathogen effectors to produce TIR-catalyzed signaling molecules for activation of plant immunity.Plant immune signaling by TIR-containing NLR(TNL)proteins converges on Enhanced Disease Suscepti-bility 1(EDS1)and its direct partners Phytoalexin Deficient 4(PAD4)or Senescence-Associated Gene 101(SAG101).TNL signaling also require helper NLRs N requirement gene 1(NRG1)and activated disease resistance 1(ADR1).In two recent remarkable papers published in Science,the authors show that the TIR-containing proteins catalyze and produce two types of signaling molecules,ADPr-ATP/diADPR and pRib-AMP/ADP.Importantly,they demonstrate that EDS1-SAG101 and EDS1-PAD4 modules are the receptor complexes for ADPr-ATP/diADPRp and Rib-AMP/ADP,respec-tively,which allosterically promote EDS1-SAG101 interaction with NRG1 and EDS1-PAD4 interaction with ADR1.Thus,two different small molecules catalyzed by TIR-containing proteins selectively activate the downstream two distinct branches of EDS1-mediated immune signalings.These breakthrough studies significantly advance our understanding of TNL downstream signaling pathway.展开更多
SARS coronavirus （SARS-CoV） develops an antagonis- tic mechanism by which to evade the antiviral activities of interferon （IFN）. Previous studies suggested that SARS-CoV papain-like protease （PLpro） inhibits act...SARS coronavirus （SARS-CoV） develops an antagonis- tic mechanism by which to evade the antiviral activities of interferon （IFN）. Previous studies suggested that SARS-CoV papain-like protease （PLpro） inhibits activa- tion of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism（s） used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro effi- ciently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain （PLpro-TM） from SARS-CoV inhibits STING/ TBKl/IKKE-mediated activation of type I IFNs and dis- rupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBKI. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKK~, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activa- tion of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is dis- rupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3- TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction withSTING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.展开更多
The hygiene hypothesis was proposed more than two decades ago,but its mechanism remains unclear.This review focuses on recent advances in the field,especially on the role played by dendritic cells(DCs)and their modula...The hygiene hypothesis was proposed more than two decades ago,but its mechanism remains unclear.This review focuses on recent advances in the field,especially on the role played by dendritic cells(DCs)and their modulating effects on various infections and allergic diseases,including allergic asthma.DCs isolated from mice long after the resolution of an infection were reported to have a significant modulating effect on allergen-specific Th2 responses in both in vitro and in vivo systems.These DCs showed DC1-like and/or tolerogenic DC capacity,which allowed for the inhibition of allergic responses by immune deviation(enhancing Th1 response)and immune regulation(through regulatory T-cell and Th2 hyporesponsiveness)mechanisms.These findings represented a significant advance in the elucidation of the mechanisms underlying the hygiene hypothesis.Further investigation on the mechanisms by which DCs are‘educated’by infectious agents and the influence of the type,time,and extent of infections on this‘education’process will help us understand immune regulation in disease settings and in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.展开更多
We previously reported that massive infiltration of neutrophils in C3H/HeN （C3H） mice could not efficiently control Chlamydia muridarum （Cm） infection and might contribute to the high susceptibility of these mice ...We previously reported that massive infiltration of neutrophils in C3H/HeN （C3H） mice could not efficiently control Chlamydia muridarum （Cm） infection and might contribute to the high susceptibility of these mice to lung infection. To further define the nature of neutrophil responses in C3H mice during chlamydial infection, we examine the expression of adhesion molecules and CDllb related to neutrophils infiltration and activation, respectively, following intranasal Cm infection. The results showed that the expression of selectins （E-selectin, P-selectin and L-selectin）, and intercellular cell adhesion molecule-1 （ICAM-1） in the lung of C3H mice increased more significantly than in C57BL/6 （B6） mice, the more resistant strain. These results correlated well with the massive neutrophils infiltration in C3H mice. In contrast, CDllb expression on peripheral blood and lung neutrophils in C3H mice exhibited a significant reduction compared with B6 mice during the late phage of infection （day 14）. These findings suggest that the high-level expression of adhesion molecules in C3H mice may enhance neutrophils recruitment to the lung, but the decline of CDllb expression on neutrophils may attenuate neutrophil function. Therefore, CDllb down-regulation on neutrophils may contribute to the failure of C3H mice to control chlamydial lung infection.展开更多
A multicenter prospective epidemiological survey on the etiologic agents of invasive candidosis was conducted in Russia in the period of 2012-2014. Samples were collected from 284 patients with invasive candidosis and...A multicenter prospective epidemiological survey on the etiologic agents of invasive candidosis was conducted in Russia in the period of 2012-2014. Samples were collected from 284 patients with invasive candidosis and Candida species isolated by culture. The species were identified by DNA sequencing and MALDI-TOF mass- spectrometry. A total of 322 isolates were recovered, in which 96% of Candida species belonged to six major species, namely, C. albicans （43.2%）, C. parapsilosis （20.2%）, C. glabrata （11.5%）, C. tropicalis （9.6%）, C. krusei （6.2%）, and C. guilliermondii （5.3%）. Most Candida species were isolated from blood samples （83.23%）. Notably, the prevalence rate of C. albicans reduced from 52.38% to 32.79% （2012 vs. 2014） （P = 0.01） whereas that of non-C. albicans increased from 47.62% （2012） to 67.21% （2014） （P〈 0.01）. Species distribution differed among geographical regions; specifically, the prevalence rate of C. albicans as an etiologic agent of invasive candidosis in Siberian Federal region was significantly higher than that in other Federal regions. Results indicated a shift from C. albicans to non-C, albicans. Therefore, a detailed investigation on the contributing factors and appropriate treatment of invasive candidosis is needed.展开更多
Cellular ＆ Molecular Immunology（2012） 9, 367-368; doi：10.lO38/cmi.2012.27; published online 7 September 2012In recent years, follicular helper T （TFH） cells have become a hot topic for immunologists due to their...Cellular ＆ Molecular Immunology（2012） 9, 367-368; doi：10.lO38/cmi.2012.27; published online 7 September 2012In recent years, follicular helper T （TFH） cells have become a hot topic for immunologists due to their pivotal role in modulatingantlbocly-mealatea immune responses.by their unique surface marker展开更多
Chemokines and their receptors are important mediators of leukocyte trafficking and recruitment and sometimes work as modulators of T-cell responses during infections and inflammation.Modulating the biological activit...Chemokines and their receptors are important mediators of leukocyte trafficking and recruitment and sometimes work as modulators of T-cell responses during infections and inflammation.Modulating the biological activity of chemokines has been found to influence the course of diseases.However,little is known about the role of chemokine responses during chlamydial lung infections.We therefore analyzed the dynamics of multiple chemokines,which are frequently associated with type 1(Th1)T cell immune responses,and their receptors for their expression in the lungs during Chlamydia muridarum(Cm)infections.We also examined the relationship between chemokine responses and the development of Th1 responses as well as the clearance of infection.Our results showed that in parallel with the high levels of gamma interferon(IFN-c)and IL-12 production in the lungs and draining lymph nodes,and the expansion of IFN-c-producing CD4 and CD81 T cells,the production of the cell-related chemokines RANTES,IFN-c-inducible protein-10(IP-10)and macrophage inflammatory protein-1a(MIP-1a)and their receptor CCR1 was elevated in the lung tissues after infection.Interestingly,in a later phase of infection,the expression of RANTES and IP-10 remained elevated but the expression of MIP-1a and CCR1 decreased to a low level,which suggests a closer association with the pattern of Th1 cytokine responses in the process of infection.These results suggest a close association between the MIP-1a response and the Th1-type T-cell responses in chlamydial lung infections .展开更多
基金the Wenzhou Municipal Science and Technology Bureau Program,Grant/Award Number:Y2023075the Key R&D Program of Zhejiang Province,Grant/Award Number:2020C03029+2 种基金the Natural Science Foundation of Zhejiang,Grant/Award Number:LQ22H160010the General Scientific Research Projects of the Zhejiang Provincial Education Department,Grant/Award Number:Y202147055Wenzhou Major Scientific and Technological Innovation Project,Grant/Award Number:ZY2022015。
文摘As one of the most prevalent gastrointestinal malignancies in humans,gastric cancer(GC)is often detected at an advanced stage,resulting in a poor prognosis and ranking it the fifth leading cause of cancer-related deaths.Due to their high genomic correlation with humans,mice are ideal in vivo models for investigating GC-related pathogenesis and therapeutic interventions.This review provides an overview of different GC models,including genetically engineered,transplantation-based models,and chemically or biologically induced models,and discusses the recent advancements for each type,highlighting their unique contributions to the field.In addition,it summarizes the strengths,limitations,and typical applications of these models and offers a critical assessment of their applicability in research while acknowledging their current limitations in fully mirroring human GC progression.Furthermore,we analyze how each model accurately recapitulates the complexities of human GC and evaluate their potential for clinical translation.This review provides a reference for model selection in future GC research.
基金supported by Zhongshan Major Science and Technology Project(2022A1004).
文摘Extracellular vesicles(EVs)have emerged as a promising technology for diagnostic and therapeutic applications in clinical settings over the past decade.However,their advancement is hindered by complex technological and regulatory challenges.This review outlines key considerations in the manufacturing process,quality management,and nonclinical evaluation relevant to EV-based drug development.Furthermore,we summarize and compare technical regulatory requirements across major countries to help clarify the regulatory principles governing EV products.Our analysis reveals an ongoing international debate regarding the regulatory review of EVs.Nevertheless,adopting a risk-based classification framework that categorizes EV products as advanced therapeutic drugs is a rational approach.Critical challenges include the development of standardized production protocols,a clearer understanding of therapeutic mechanisms,and resolving complex regulatory issues.
基金Supported by Project of Science and Technology Commis sion Foundation of Jiangsu Province in 1998
文摘Objective: To observe the clinical effect of Rebixiao granule (热痹消颗粒剂, RBXG) in treating repeatedly attacking acute gouty arthritis and through experimental study on blood uric acid to explore RBXG's therapeutic mechanism. Methods: Ninety repeatedly attacking acute gouty arthritis patients were divided into the treated group ( n =60) and control group ( n =30). The treated group was treated with RBXG, and the control group was treated with Futalin tablets (diclofenac sodium). The baseline treatment including good rest, low purine diet, sufficient water drinking and urine alkalization, etc. was then given to both groups. Hypoxanthine 600 mg/kg and niacin 100 mg/kg was applied to hyperuricemic mice by gastrogavage to establish the animal models. Results: The clinical effective rate of the treated group was 95.0% and that of the control 90.0%. Good therapeutic effects were won, insignificant difference ( P >0.05)was shown between the two groups. However, the cure rate of the treated group was 26.7% while that of the control group was 10.0%, with significant difference ( P <0.01) shown between them. The treated group had its blood uric acid lowered, which was significantly different ( P <0.05) from that of the control group. The animal experiment indicated that all the three groups treated with different dosages of RBXG, as well as the Ash bark and Smilax glabra rhizome groups had their blood uric acid content reduced in the hyperuricemic mice. Conclusion: RBXG has a quicker initiation and better treatment effects than sole anti-inflammatory and analgesic agents on the treatment of repeatedly attacking acute gouty arthritis, showing no obvious toxic or adverse reactions and therefore good for long-term administration and likely to be a safe TCM preparation to control the symptoms and reduce the onsets of repeatedly attacking of acute gouty arthritis. The animal experiment shows that both the compound preparation and part of the single ingredients in the recipe have the function of reducing blood uric acid. However, the compound recipe has better therapeutic effects, proving to be superior to single drugs.
基金This study was funded by grants from the National Natural Science Foundation of China(81601787,81871681)the Natural Science Foundation of Jiangsu Province(BK20160192)+3 种基金the Fundamental Research Funds for the Central Universities funded by the Ministry of Education of China(JUSRP51710A)the Bill and Melinda Gates Foundation(OPP1161962)China Medical Boardthe National First-Class Discipline Program of Food Science and Technology(JUFSTR20180101).
文摘China's participation in global governance,inspired by the 17 United Nations Sustainable Development Goals,is driven by the guiding principle of"Building a Community of Shared Future for Mankind".China has been promoting the Belt and Road Initiative and South-South Cooperation and has made significant contributions to the prosperity of human beings.Along with the opportunities that globalization brought about such as the World Health Organization and the boom in the economy,global health challenges also emerged.This resulted in certain obstacles for China when it sought to advocate the Belt and Road Initiative and when it attempted to carry out its strategy to address global health issues.What are the emerging challenges for global health?What can China do for global health?Why does global health need China?We tried to address these questions as China's global engagement continues to expand in the new era.This article makes the case for Chinese approaches,including getting involved in public health,being consistent in addressing local conditions,and sharing China's experience with handling health services and staying in the lead through government action while being guided by relative policies.China has a lot to offer in the promotion of global health and in overcoming the challenges and risks that this goal currently faces.Thus,China should be considered an inseparable part of global health governance and bilateral health development cooperation.
文摘Objective: To study the effect of adding different concentrations of soybean lecithin in Tris based extender and to compare the results of Tris soybean lecithin extender with two commercial diluents (egg yolk-based: BullXcell and plant-based: OptiXcell) for Damascus goat sperm cryopreservation. Methods: The ejaculates from 4 mature male Damascus goats were obtained by using an artificial vagina. Semen samples were pooled and diluted in Tris extender supplemented with soybean lecithin at different concentrations of 1.5%, 3.0%, 6.0% and 10.0% to get better concentration to be used for further experiments, with a final concentration of 240×106 spermatozoa/mL. Semen samples were packed in straws (0.25 mL), frozen by using an automated system and stored in liquid nitrogen at -196 ℃ for 48 h. After thawing (37 ℃/30 s), the samples were evaluated for sperm quality parameters, including sperm motility, membrane integrity and acrosome integrity. Malondialdehyde concentration was estimated as a marker for lipid peroxidation. Based on the previous investigations, only Tris extender supplemented with 3.0% soybean lecithin (based on its positive results) was used versus BullXcell and OptiXcell for sperm ultrastructure evaluation and artificial insemination by using electron microscope and artificial insemination of the synchronized does. Results: There was no significant difference between Tris-soybean lecithin at 3.0% and BullXcell/OptiXcell diluents in post-thaw sperm parameters and fertility following artificial insemination;meanwhile, the other concentrations of soybean lecithin (1.5%, 6.0% and 10%) showed lower sperm parameters following cryopreservation. Conclusions: Using of Tris-soybean lecithin based extender at the level of 3.0% can be an appropriate alternative to either BullXcell or OptiXcell for Damascus goat sperm cryopreservation.
基金The Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period of China (2008ZX10001-002)the Major Science and Technology Innovation Cross Project of the Chinese Academy of Sciences (KSCX1-YW-10)
文摘This study aimed to evaluate emerging trends of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) among 290 former blood donor HIV-1 infected patients in Hubei, China, from 2004 to 2006, all of whom had received anti-HIV-1 therapy. The presence of NRTI- and NNRTI-associated mutations were established by sequencing; genotypic and predicted phenotypic drug resistance were evaluated using HIVdb Program version 5.0.1 (http://hivdb.stanford.edu/ pages/algs/HIVdb.html). Genotypic drug resistance analysis showed significant increases in percentages of patients carrying HIV-1 strains with M41L, T215Y/F, D67N, K103N, G190A/S, Y181C/F or L210W mutations. Of the variants' predicted phenotypic drug resistance, highly significant increases were detected in percentages of patients carrying HIV-1 with high resistance to zidovudine (AZT) or stavudine (D4T) in NRTIs, and to delavirdine (DLV), efavirenz (EFV) or nevirapine (NVP) in NNRTIs; intermediate resistance to abacavir (ABC), AZT, D4T, didanosine (DDI) or tenofovir disoproxil fumarate (TDF) in NRTIs, and to etravirine (ETR) in NNRTIs; and low and potential low resistance to lamivudine (3TC), ABC, emtricitabine (FTC) or TDF in NRTIs, and to ETR in NNRTIs.
基金Supported by AA and MDSIF research grant to Pu JJ,No.146818American Cancer Society grant to Pu JJ,No.124171-IRG-13-043-02a Pennsylvania State University College of Medicine research grant to Pu JJ
文摘Acquired bone marrow failure diseases(ABMFD) are a class of hematopoietic stem cell diseases with a commonality of non-inherited disruption of hematopoiesis that results in pancytopenia. ABMFDs also are a group of heterogeneous diseases with different etiologies and treatment options. The three most common ABMFDs are aplastic anemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria. Stem cell transplantation is the only treatment that can cure these diseases. However, due to high therapy-related mortality, stem cell transplantation has rarely been used as a first line treatment in treating ABMFD. With the advance of personalized medicine and precision medicine, various novel cellular therapy strategies are in trial to increase the efficiency and efficacy of ABMFD treatment. This article aims to review current available stem cell transplantation protocols and promising cellular therapy research in treating ABMFD.
文摘Objectives: Although the naphthoquinone, 7-methyljuglone (7-MJ), is active against Mycobacterium tuberculosis (MTB) in vitro, neither the cellular site nor mechanism of anti-mycobacterial action of this agent has been identified. The primary objective of the current study was to investigate the mycobacterial outer membrane as a potential target of 7-MJ by measuring the effects of this agent (0.023 - 1.5 mg/L) on microbial ATP levels and uptake of K+ . Methods: Bioluminescence and radiometric (uptake of 86Rb+) procedures were used to assay microbial ATP levels and K+ transport respectively. Results: Exposure of MTB (strain H37Rv) to 7-MJ for 60 min resulted in dose-related decreases in both microbial ATP levels and uptake of 86Rb+ which achieved statistical significance (P + transport.
文摘Objective: to analyze the adverse reactions of DPT vaccination in children, and to explore the relevant preventive countermeasures and application effect. Methods: in January 2020, Lianyun District began to actively implement the preventive intervention measures of adverse reactions to pediatric DPT vaccination, Children who have completed the vaccination of prevention countermeasures in Lianyun District before the implementation of this study (January 1,2017 to December 31,2019) and after the implementation (January 1,2020 to December 31,2021). As the routine guidance group (23,921 doses) and the preventive intervention group (11,383 doses), monitoring the adverse reactions and satisfaction with vaccination care in both groups, analyze the effects of the preventive intervention. Results: the general response (0.31%) and total incidence of adverse reaction (0.31%) were significantly lower than the conventional guidance group (0.18%, 0.18%) (P <0.05), and the incidence of abnormal response between the two groups (P> 0.05). Parent satisfaction with vaccination care in the preventive intervention group (99.90%) was significantly higher than that in the conventional guidance group (92.75%) (P <0.05). Conclusion: there are some risks of adverse reactions after vaccination with DPT vaccine, mainly general reactions, which can reduce the risk of adverse reactions and have high application value, which is worth promotion and reference.
文摘Aim: To investigate the effects of exposure of a macrolide-resistant [erm (B)-expressing] strain of Streptococcus pneumoniae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. Methods: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was performed using reverse transcription-PCR and sequencing. Results: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibiotic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or competence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. Conclusions: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.
文摘Follicular helper T （TFH） cells represent a distinct subset of CD4＋ helper T （TH） cells specialized in providing help to B cells. They are characterized by their unique transcriptional profile （Bcl6）, surface marker expression （CXCR5, PD-1, ICOS and CD4OL） and cytokine production pattern （IL-21 and IL-6）. TFH cells provide help to B cells both to form germinal centers （GCs） and to differentiate into memory B cells and plasma cells for generation of humoral responses. However, there is emerging evidence that implicates TFH cells in the development of various human pathologies, such as autoimmune diseases, immunodeficiency and lymphoma. This review focuses on the current progress in this area including mouse and human studies. A clearer understanding of the mechanisms of TFH cell-mediated immunity and pathology may be exploited for rational development of therapeutic strategies. Cellular＆ Molecular Immunology（2012） 9, 380-385; doi：10.1038/cmi.2012.26; published online 13 August 2012
基金This research was supported by grants from the National Natural Science Foundation of China （Grant Nos. 81273231,81172799 to Z. C. and 81102478, 81471947 to Y. X.）.
文摘Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 （PLP2-TM） of coronaviruses acts as a novel autophagy- inducing protein. Intriguingly, PLP2-TM induces incom- plete autophagy process by increasing the accumula- tion of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2- TM interacts with the key autophagy regulators, LC3 and Beclinl, and promotes Beclinl interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclinl partially reverses PLP2-TM＇s inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results sug- gested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclinl, which in turn modulates coronavirus replication and antiviral innate immunity.
基金support from the National Natural Science Foundation of China(31925032 and 31870143).
文摘Plant intracellular nucleotide-binding leucine-rich repeat(NLR)receptors with an N-terminal Toll/Interleukin-1 recep-tor(TIR)domain detect pathogen effectors to produce TIR-catalyzed signaling molecules for activation of plant immunity.Plant immune signaling by TIR-containing NLR(TNL)proteins converges on Enhanced Disease Suscepti-bility 1(EDS1)and its direct partners Phytoalexin Deficient 4(PAD4)or Senescence-Associated Gene 101(SAG101).TNL signaling also require helper NLRs N requirement gene 1(NRG1)and activated disease resistance 1(ADR1).In two recent remarkable papers published in Science,the authors show that the TIR-containing proteins catalyze and produce two types of signaling molecules,ADPr-ATP/diADPR and pRib-AMP/ADP.Importantly,they demonstrate that EDS1-SAG101 and EDS1-PAD4 modules are the receptor complexes for ADPr-ATP/diADPRp and Rib-AMP/ADP,respec-tively,which allosterically promote EDS1-SAG101 interaction with NRG1 and EDS1-PAD4 interaction with ADR1.Thus,two different small molecules catalyzed by TIR-containing proteins selectively activate the downstream two distinct branches of EDS1-mediated immune signalings.These breakthrough studies significantly advance our understanding of TNL downstream signaling pathway.
文摘SARS coronavirus （SARS-CoV） develops an antagonis- tic mechanism by which to evade the antiviral activities of interferon （IFN）. Previous studies suggested that SARS-CoV papain-like protease （PLpro） inhibits activa- tion of the IRF3 pathway, which would normally elicit a robust IFN response, but the mechanism（s） used by SARS PLpro to inhibit activation of the IRF3 pathway is not fully known. In this study, we uncovered a novel mechanism that may explain how SARS PLpro effi- ciently inhibits activation of the IRF3 pathway. We found that expression of the membrane-anchored PLpro domain （PLpro-TM） from SARS-CoV inhibits STING/ TBKl/IKKE-mediated activation of type I IFNs and dis- rupts the phosphorylation and dimerization of IRF3, which are activated by STING and TBKI. Meanwhile, we showed that PLpro-TM physically interacts with TRAF3, TBK1, IKK~, STING, and IRF3, the key components that assemble the STING-TRAF3-TBK1 complex for activa- tion of IFN expression. However, the interaction between the components in STING-TRAF3-TBK1 complex is dis- rupted by PLpro-TM. Furthermore, SARS PLpro-TM reduces the levels of ubiquitinated forms of RIG-I, STING, TRAF3, TBK1, and IRF3 in the STING-TRAF3- TBK1 complex. These results collectively point to a new mechanism used by SARS-CoV through which PLpro negatively regulates IRF3 activation by interaction withSTING-TRAF3-TBK1 complex, yielding a SARS-CoV countermeasure against host innate immunity.
基金This work was supported by operating grants from the Canadian Institutes for Health Research(CIHR)the Manitoba Health Research Council(MHRC)to XY.
文摘The hygiene hypothesis was proposed more than two decades ago,but its mechanism remains unclear.This review focuses on recent advances in the field,especially on the role played by dendritic cells(DCs)and their modulating effects on various infections and allergic diseases,including allergic asthma.DCs isolated from mice long after the resolution of an infection were reported to have a significant modulating effect on allergen-specific Th2 responses in both in vitro and in vivo systems.These DCs showed DC1-like and/or tolerogenic DC capacity,which allowed for the inhibition of allergic responses by immune deviation(enhancing Th1 response)and immune regulation(through regulatory T-cell and Th2 hyporesponsiveness)mechanisms.These findings represented a significant advance in the elucidation of the mechanisms underlying the hygiene hypothesis.Further investigation on the mechanisms by which DCs are‘educated’by infectious agents and the influence of the type,time,and extent of infections on this‘education’process will help us understand immune regulation in disease settings and in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.
文摘We previously reported that massive infiltration of neutrophils in C3H/HeN （C3H） mice could not efficiently control Chlamydia muridarum （Cm） infection and might contribute to the high susceptibility of these mice to lung infection. To further define the nature of neutrophil responses in C3H mice during chlamydial infection, we examine the expression of adhesion molecules and CDllb related to neutrophils infiltration and activation, respectively, following intranasal Cm infection. The results showed that the expression of selectins （E-selectin, P-selectin and L-selectin）, and intercellular cell adhesion molecule-1 （ICAM-1） in the lung of C3H mice increased more significantly than in C57BL/6 （B6） mice, the more resistant strain. These results correlated well with the massive neutrophils infiltration in C3H mice. In contrast, CDllb expression on peripheral blood and lung neutrophils in C3H mice exhibited a significant reduction compared with B6 mice during the late phage of infection （day 14）. These findings suggest that the high-level expression of adhesion molecules in C3H mice may enhance neutrophils recruitment to the lung, but the decline of CDllb expression on neutrophils may attenuate neutrophil function. Therefore, CDllb down-regulation on neutrophils may contribute to the failure of C3H mice to control chlamydial lung infection.
基金We acknowledge the management of Russian Ministry of Health and Sino-Russian Medical Research Center of Heilongjiang Academy of Medical Sciences, China which offered finance support, laboratory space, and equipment used in this research. We also acknowledge specific clinics and hospitals that helped in collecting clinical samples. This research was financially supported by Russian Ministry of Health, Russia Sino-Russian Medical Research Center of Heilongjiang Academy of Medical Sciences, China （Nos. CR201406 and CR201502）, National Natural Science Foundation of China （No.81301703） and Natural Science Foundation of Heilongjiang Province, China （No. QC2013C078）.
文摘A multicenter prospective epidemiological survey on the etiologic agents of invasive candidosis was conducted in Russia in the period of 2012-2014. Samples were collected from 284 patients with invasive candidosis and Candida species isolated by culture. The species were identified by DNA sequencing and MALDI-TOF mass- spectrometry. A total of 322 isolates were recovered, in which 96% of Candida species belonged to six major species, namely, C. albicans （43.2%）, C. parapsilosis （20.2%）, C. glabrata （11.5%）, C. tropicalis （9.6%）, C. krusei （6.2%）, and C. guilliermondii （5.3%）. Most Candida species were isolated from blood samples （83.23%）. Notably, the prevalence rate of C. albicans reduced from 52.38% to 32.79% （2012 vs. 2014） （P = 0.01） whereas that of non-C. albicans increased from 47.62% （2012） to 67.21% （2014） （P〈 0.01）. Species distribution differed among geographical regions; specifically, the prevalence rate of C. albicans as an etiologic agent of invasive candidosis in Siberian Federal region was significantly higher than that in other Federal regions. Results indicated a shift from C. albicans to non-C, albicans. Therefore, a detailed investigation on the contributing factors and appropriate treatment of invasive candidosis is needed.
文摘Cellular ＆ Molecular Immunology（2012） 9, 367-368; doi：10.lO38/cmi.2012.27; published online 7 September 2012In recent years, follicular helper T （TFH） cells have become a hot topic for immunologists due to their pivotal role in modulatingantlbocly-mealatea immune responses.by their unique surface marker
基金supported by a fund from the Tianjin Municipal Science and Technology Commission(07JCYBJC10600).
文摘Chemokines and their receptors are important mediators of leukocyte trafficking and recruitment and sometimes work as modulators of T-cell responses during infections and inflammation.Modulating the biological activity of chemokines has been found to influence the course of diseases.However,little is known about the role of chemokine responses during chlamydial lung infections.We therefore analyzed the dynamics of multiple chemokines,which are frequently associated with type 1(Th1)T cell immune responses,and their receptors for their expression in the lungs during Chlamydia muridarum(Cm)infections.We also examined the relationship between chemokine responses and the development of Th1 responses as well as the clearance of infection.Our results showed that in parallel with the high levels of gamma interferon(IFN-c)and IL-12 production in the lungs and draining lymph nodes,and the expansion of IFN-c-producing CD4 and CD81 T cells,the production of the cell-related chemokines RANTES,IFN-c-inducible protein-10(IP-10)and macrophage inflammatory protein-1a(MIP-1a)and their receptor CCR1 was elevated in the lung tissues after infection.Interestingly,in a later phase of infection,the expression of RANTES and IP-10 remained elevated but the expression of MIP-1a and CCR1 decreased to a low level,which suggests a closer association with the pattern of Th1 cytokine responses in the process of infection.These results suggest a close association between the MIP-1a response and the Th1-type T-cell responses in chlamydial lung infections .
