Pattern recognition receptors (PRRs) play a crucial role in immune responses, acting as primary sensors for microbial and host-derived signals. PRRs, which include Toll-like receptors (TLRs), retinoic acid-inducible gene 1-like receptors, nucleotide-binding oligomerization domain-like receptors, C-type lectin receptors, and various cytoplasmic DNA sensors, are essential for initiating immune responses that regulate both inflammation and tumor immunity. Recent studies have highlighted their dual roles in cancer, where they can either suppress or promote tumor progression by influencing the tumor microenvironment and modulating responses to immunotherapy. In the context of cancer, PRRs not only activate immune cells but also contribute to immune evasion mechanisms within tumors. Therapeutically, targeting PRRs represents a promising approach for cancer treatment, with related drugs showing potential to enhance the efficacy of existing immunotherapies. Numerous PRR-based agents, particularly TLR agonists, are currently under clinical investigation for their ability to augment antitumor immunity and overcome resistance to immune checkpoint inhibitors. This review examines the molecular mechanisms by which PRRs influence cancer, with a focus on recent advancements in PRR-targeted therapies and their integration with contemporary immunotherapeutic strategies.

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*

AIM: To compare the effects of different doses of alfentanil on tracheal intubation conditions, hemodynamic parameters and recovery quality in children undergoing tonsillectomy. METHODS: Ninety children undergoing tonsillectomy were randomly divided into 3 groups, and received alfentanil 20 μg/kg (A20 group), 40 μg/kg (A40 group) and 60 μg/kg (A60 group) for anesthesiainduction respectively, 30 cases in each group. The remaining anesthesia induction and maintenance protocols were the same. The Helbo-Hansen scores of the three groups were evaluated, and the MAP and HR before anesthesia induction (T0), before tracheal intubation (T1), immediately after tracheal intubation (T2), and 1 min after intubation (T3) as well as the recovery time of spontaneous breathing, eye opening time, extubated time, agitation score in PACU, and adverse drug reactions were recorded. RESULTS: Compared with A20 group, the total values of Helbo-Hansen score and cough scores in group A40 and A60 were lower (P<0.05). Compared with T0, the MAP at T1-T3 were decreased in group A40 and A60, and HR increased at T2 and T3 in group A20 while HR slowed down at T1 in group A40, and at T1-T3 in group A60 (P<0.05). Compared with A20 group, children in group A40 had lower MAP and slower HR at T1-T3, while those in group A60 had lower MAP and slower HR at T1-T3 (P<0.05). The recovery time of spontaneous breathe and extubated time were prolonged in group A60 (P<0.05). CONCLUSION: During the anesthesia induction period of tonsillectomy in children, both afentanil 40 μg/kg or 60 μg/kg combined with propofol 3 mg/kg and rocuronium 0.3 mg/kg can provide satisfactory intubation condition, while the vital signs are more stable during anesthesia induction in afentanil 40 μg/kg group and rapid extubation after operation can be achieved.

AIM: To explore whether necroptosis contributes to the high glucose (HG)-induced damage in hu-man umbilical vein endothelial cells (HUVECs).METHODS: The protein levels of receptor-interacting protein 3 (RIP3) and cleaved caspase-3 were detected by Western blot.The intracellular levels of reactive oxygen species (ROS) were deter-mined by DCFH-DA staining followed by photofluorography.Mitochondrial membrane potential (MMP) was measured by rhodamine 123 staining followed by photofluorography.RESULTS: Treatment of HUVECs with HG at different concentra-tions (10, 20 and 40 mmol/L glucose) for 24 h gradually enhanced the expression levels of RIP3.Treatment of HUVECs with HG (40 mmol/L glucose) for different time (3 h, 6 h, 9 h, 12 h and 24 h) also up-regulated the expression levels of RIP3, peaking at 9 h.Pretreatment of HUVECs with 20 μmol/L Z-VAD-FMK (an inhibitor of caspase) for 30 min before exposure to HG enhanced the expression level of RIP3.Pretreatment of HUVECs with 100 μmol/L necrostatin-1 (an inhi-bitor of necroptosis) for 1 h before exposure to HG alleviated the HG-induced injuries, such as a decrease in cell viability, an increase in ROS generation and dissipation of MMP, but up-regulated the protein level of cleaved caspase-3.CON-
CLUSION: Necroptosis mediates HG-induced injury in HUVECs.There is a negative interacting between necroptosis and apoptosis.

Objective To observe the effects of a motor relearning programme (MRP) combined with different early acupuncture interventions on muscle tension and motor function recovery after cerebral infarction.MethodsA total of 90 patients with cerebral infarction who met the inclusion criteria were divided into three groups at random:a YANGMING meridian acupuncture and MRP group ( group A),an anti-spasm acupuncture and MRP group ( group B),and an MRP group ( group C ).All of the patients in all three groups were treated with routine medication.The National Institute of Health stroke scale (NIHSS),the composite spasticity scale (CSS),Fugl-Meyer assessment (FMA),the Fugl-Meyer balance scale (FM-B) and the modified Barthel index (MBI) were used to measure performance before treatment and after 4 weeks of treatment.Another comparison was intra-group between before and after treatment. ResultsThere were significant differences in the assessment results in all of the groups after treatment compared with those before treatment.After treatment,group B was superior to group C only in terms of NIHSS scores.There was no significant NIHSS score difference between groups A and C.The FMA,CSS and MBI results revealed significant differences among all three groups,with the scores of group A consistently the highest.The average FMA score in group B was significantly higher than in group C but there was no statistically significant difference in FM-B scores among the three groups. ConclusionMRP therapy combined with early acupuncture intervention can improve motor function and muscular tension after cerebral infarction.Anti-spasm acupuncture can improve motor function and control muscular tension effectively at the same time,making it beneficial for MRP training.

OBJECTIVETo evaluate the risk of nasopharyngeal carcinoma (NPC) through EB virus antibody profile by enzyme linked immunosorbent assay (ELISA).

METHODSEBNA 1/IgA, EBNA 1/IgG and zta/IgG by ELISA and VCA/IgA by immmunoenzymatic method were detected in 121 NPC patients and 332 healthy subjects (HS) in the Pearl river estuary.

RESULTSThe sensitivity rates were 85%, 83% and 79% for EBNA 1/IgA, EBNA 1/IgG and zta/IgG, all three of which if combined was the highest 92%. The specificity rates were 86%, 86% and 80% for EBNA 1/IgA, EBNA 1/IgG and zta/IgG, all three of which if combined was also the highest 93%. According to the level of odds ratio, nasopharyngeal carcinoma risk could be divided into 3 groups: low, moderate and high-risk groups. 93% of HS had low risk of NPC with the odds ratio 0.0 to 0.3. 0.4% of HS had high risk of NPC with the odds ratio of 137.9%.

CONCLUSIONELISA is more objective than the traditional immunoenzymatic method in the detection and diagnosis of NPC. The combination of EBNA 1/IgA, EBNA 1/IgG and zta/IgG is able to evaluate the risk of NPC.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Viral ; analysis ; Enzyme-Linked Immunosorbent Assay ; Epstein-Barr Virus Nuclear Antigens ; analysis ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; virology ; Risk Factors

AIM: To explore the role of extracellular signal-regulated kinases ERK1/2-STAT3 pathway in adaptive cytoprotection induced by H2O2 preconditioning in PC12 cells.METHODS: In PC12 cells,the experimental model of cytoprotection by H2O2 preconditioning against oxidative stress-induced injury was set up.The morphological changes in the apoptotic cells were observed by using of chromatin dye Hoechst 33258.The percent of apoptotic cells was determined by flow cytometry(FCM) with propidium iodide staining.The levels of p-ERK1/2 and p-STAT3 expression were detected by Western blotting assay.RESULTS: Preconditioning with H2O2 at concentration of 100 ?mol/L for 90 min obviously inhibited apoptosis induced by 300 ?mol/L H2O2,and both ERK1/2 and STAT3 were activated.UO126(10 ?mol/L,an inhibitor of ERK1/2) or AG-490(10?mol/L,an inhibitor of JAK2) significantly blocked the cytoprotection effect of H2O2 preconditioning.Moreover,UO126(10 ?mol/L) also markedly inhibited the up-regulation of p-STAT3 expression by H2O2 preconditioning.CONCLUSION: H2O2 preconditioning activates ERK1/2-STAT3 signal pathway,which may be one of the mechanisms underlying H2O2 preconditioning-induced cytoprotection.