Interleukin-1 receptor-related kinase (IRAK4) is a widely expressed serine/threonine kinase involved in the regulation of innate immunity. IRAK4 plays a pivotal role as a key kinase within the downstream signaling pathway cascades of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs). The signaling pathways orchestrated by IRAK4 are integral to inflammatory responses, and its overexpression is implicated in the pathogenesis of inflammatory diseases, autoimmune disorders, and cancer. Consequently, targeting IRAK4-mediated signaling pathways has emerged as a promising therapeutic strategy. Small molecule inhibitors and degraders designed to modulate IRAK4 have shown efficacy in mitigating related diseases. In this paper, we will provide a detailed description of the structure and function of IRAK4, the role of IRAK4 in related diseases, as well as the currently reported small molecule inhibitors and degraders of IRAK4. It is expected to provide new directions for enriching the clinical treatment of inflammation and related diseases.

Objective To investigate the clinical significance and changes of serum complement in lipid metabolism disorder in patients with fatty liver disease.Methods One hundred and forty patients with FLD from October 2015 to May 2017 were included in the study,in addition,120 patients with hyperlipidemia(the hyperlipidemia group)and 130 healthy subjects(the control group)in the same period were enrolled as controls.The differences in serum lipid,liver function enzymology,immunoglobulin,serum complement among the three groups were compared.Results There were significant differences in the levels of TC,TG,HDL-C,LDL-C,apoA and apoB among the three groups(TC:(5.7±1.6)mmol/L vs.(4.2±1.0)mmol/L vs.(3.5±1.1) mmol/L,F=105.01,P<0.05;TG:(2.8± 0.6)mmol/L vs.(1.5 ± 0.3)mmol/L vs.(1.1 ± 0.2)mmol/L,F=628.46,P<0.05;HDL-C:(1.2±0.3)mmol/L vs.(1.5±0.3)mmol/L vs.(1.8±0.4)mmol/L,F=107.10, P<0.05;LDL-C:(3.6±0.9)mmol/L vs.(3.0±0.8)mmol/L vs.(2.2±0.6)mmol/L,F=109.07,P<0.05;apoA:(1.0±0.2)g/L vs.(1.2±0.2)g/L vs.(1.4±0.3)g/L,F=95.20,P<0.05;apoB:(1.1±0.2)g/L vs.(0.9±0.2)g/L vs.(0.8±0.2)g/L,F=79.04,P<0.05).The levels of TC,TG,LDL-C and apoB in the FLD group were significantly higher than those in the hyperlipidemia group and the control group.The levels of HDL-C and apoA in the FLD groups were significantly lower than those in the hyperlipidemia group and control group.The levels of TC,TG,LDL-C and apoB in the hyperlipidemia group were significantly higher than those in the control group.The levels of HDL-C and apoA in the hyperlipidemia group were significantly lower than those in the control group.There were significant differences in the levels of GGT,ALT,AST,IgG and IgM among the three groups(GGT:(77.4±15.3)U/L vs.(43.3±10.6)U/L vs.(25.5±8.2)U/L,F=668.12,P<0.05;ALT:(61.5±18.8)U/L vs.(35.7±11.2)U/L vs.(18.9±5.4)U/L,F=355.67,P<0.05;AST:(55.3±12.2)U/L vs.(32.4±12.5)U/L vs.(14.4±4.7)U/L,F=521.80,P<0.05;IgG:(15.7±3.9)g/L vs.(11.6±3.2)g/vs.,(8.5±2.6)g/L,F=162.34,P<0.05;IgM:(1.9±0.6)g/L vs.(1.2±0.4)g/L vs.(0.8±0.3)g/L,F=201.38,P<0.05).The levels of GGT,ALT,AST,IgG and IgM in the FLD group were significantly higher than those in the hyperlipidemia group and the control group.The levels of GGT,ALT,AST,IgG and IgM in the hyperlipidemia group were significantly higher than those in the control group.There were significant differences in the levels of C3,C5,ASP and BF among the mild,moderate and severe fatty liver patients(C3:(2.1±0.4) g/L vs.(1.8±0.3)g/L vs.(1.0±0.2)g/L,F=436.37,P<0.05;C5:(92.3±10.7)mg/L vs.(71.8±8.8) mg/L vs.(58.9±6.5)mg/L,F=486.09,P<0.05; ASP:(51.4±6.8)nmol/L vs.(42.5±4.4)nmol/L vs.(32.8±5.2)nmol/L,F=369.29,P<0.05;BF:(0.48±0.13)g/L vs.(0.34±0.09)g/L vs.(0.23±0.04) g/L,F=233.39,P<0.05).The levels of C3,C5,ASP and BF in the FLD group were significantly higher than those in the hyperlipidemia group and the control group.The levels of C3,C5,ASP and BF in the hyperlipidemia group were significantly higher than those in the control group.There were significant differences in the levels of C3,C5,ASP and BF among patients with mild,moderate and severe fatty liver disease(C3:(1.8±0.3)g/L vs.(2.1±0.4)g/L vs.(2.5±0.4)g/L,F=30.85,P<0.05;C5:(80.5±9.6)mg/L vs.(92.3±10.5)mg/L vs.(100.7±8.)mg/L,F=39.39,P<0.05; ASP:(42.4±6.3)nmol/L vs.(52.8±5.7)nmol/L vs.(61.9±5.6) nmol/L,F=98.19,P<0.05;BF:(0.33±0.12)g/L vs.(0.45±0.11)g/L vs.(0.57±0.09)g/L,F=41.26,P<0.05).The levels of C3,C5,ASP and BF in the mild FLD patients were significantly lower than those in moderate and severe FLD patients.The levels of C3,C5,ASP and BF in the moderate FLD patients were significantly lower than those in severe FLD patients.Conclusion The detection of C3,C5,ASP and BF levels based on routine testes has important clinical value for the assessment of the condition,the treatment and the prognosis of FLD patients.

Objective To explore the relationship between human papilloma virus (HPV) infected population and disease occur‐rence in order to provide evidence and some reasonable suggestions for people understanding this disease .Methods A total of 2 508 suspected patients in our hospital from August 2012 to August 2013 were performed the HPV subtype detection by using PCR‐re‐verse dot blot(RDB) ,including 18 kinds of high risk HPV subtypes(HPV16 ,18 ,31 ,33 ,35 ,39 ,45 ,51 ,52 ,53 ,56 ,58 ,59 ,66 ,68 ,73 , 83 ,MM4) and 5 kinds of low risk HPV subtypes (HPV6 ,11 ,42 ,43 ,44) .Finally ,the patients condition was tracked through the hospital information management system and the clinical laboratory information systems .Results The HPV detection rate was 12 .26% ,in which the high risk type was mainly HPV 52 ,accounting for 12 .66% ,followed by HPV 58 ,16 .The low risk types were mainly HPV 43 ,6 ,11 ,accounting for 14 .61% ,10 .39% and 8 .44% respectively .By the follow up observation of clinical outcomes , the homotype positive phenomena were repeatedly appeared in the patients infected by HPV 52 ,16 within 2 years .At the same time ,the thinprep cytologist test(TCT) results in 157 cases of high risk HPV infection (genotype 52 ,58 ,16 ,18 ,66 ,33 ,56 ,68) were performed the tracking analysis ,indicating that high risk HPV infection was closely associated with cervical intraepithelial ne‐oplasia (CIN)Ⅰ ,CIN Ⅱ and canceration .Meanwhile ,their leucorrhea routine detection were followed up ,which manifested by mild to moderate inflammation .Conclusion High risk HPV subtype infection is closely associated with CIN Ⅰ ,CIN Ⅱ and canceration , while the leucorrhea routine shows mild ,moderate inflammation .Therefore ,only conducting the simple leucorrhea routine analysis can not really reflect the infection status ,it is necessary to look for the ways to cooperate with the superior hospital for timely detec‐ting HPV infection situation ,moreover regular follow up of people with HPV positive is the effective pathway to prevent CIN and cervical cancer .