MRGPRX2 antagonists possess the potential for the treatment of allergic rhinitis, atopic dermatitis, and chronic urticaria. Previously, we identified a class of diaryl urea (DPU) MRGPRX2 antagonists with sub-micromolar IC₅₀ values in vitro. However, the structure-activity relationship remains unclear. Herein, we adopted a "relative symmetry with electronegativity of different key-groups" strategy for further modification of DPUs to achieve a promising MRGPRX2 antagonist with higher activity and safety. Electrostatic potential energy analysis and biological evaluation revealed that B-1023 and B-5023, that possess relatively symmetric electron-withdrawing substituents, remarkable inhibited mast cell degranulation at a sub-micromolar IC₅₀ in vitro and alleviated anaphylactic symptoms. Furthermore, B-1023, mitigated antigen-induced pulmonary inflammation (AIPI) in mice and competitively bonded to MRGPRX2. In summary, the "relative symmetry with electronegativity of different key-groups" strategy provided a drug design pattern for MRGPRX2 antagonists and identified promising antiallergic precursors for AIPI treatment.

The nervous system not only affects the core processes of tumors such as proliferation, metastasis and angiogenesis, but is also closely related to symptoms such as tumor-related pain and cachexia. Meanwhile, tumor cells can invade adjacent tissues through nerve pathways to induce perineural invasion, which promotes tumor development. This article reviews the research progress in role of the nervous system in tumor occurrence and development from perspectives of tumor perineural invasion, neurotrophic factors, autonomic and sensory nerves, and influence of the neuroimmune system in tumors, in order to provide new perspective and method for tumor treatment.

The nervous system not only affects the core processes of tumors such as proliferation, metastasis and angiogenesis, but is also closely related to symptoms such as tumor-related pain and cachexia. Meanwhile, tumor cells can invade adjacent tissues through nerve pathways to induce perineural invasion, which promotes tumor development. This article reviews the research progress in role of the nervous system in tumor occurrence and development from perspectives of tumor perineural invasion, neurotrophic factors, autonomic and sensory nerves, and influence of the neuroimmune system in tumors, in order to provide new perspective and method for tumor treatment.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Infrared thermography is an advanced technology that utilizes infrared detectors to sense the infrared thermal radiation emitted from the human body's surface,converting it into electrical signals.These signals are then processed by computers to generate planar temperature color images,providing an intuitive display of the body surface temperature distribution.Rheumatic diseases,as prevalent conditions that significantly impact the quality of life of millions of people worldwide,pose significant challenges in diagnosis and assessment.Traditional diagnostic and evaluation methods,while possessing certain clinical value,exhibit non-negligible limitations.With the advancements and increasing popularity of infrared thermography technology,combined with the progress in medical image recognition and artificial intelli-gence algorithms,this technology has demonstrated increasingly prominent advantages in the field of rheu-matology.By employing this non-invasive and highly efficient technique for analyzing superficial tissue thermal radiation distribution,early and precise diagnosis of rheumatic diseases,as well as dynamic mo-nitoring of disease progression,becomes feasible.This technological advancement enhances the accuracy and efficiency of rheumatic disease diagnosis,thereby alleviating the burden on healthcare systems and optimizing the allocation of medical resources.Furthermore,infrared thermography introduces new vitality into the diagnosis and treatment monitoring of rheumatic diseases.It enables clinicians to detect subtle changes in body surface temperature that may indicate underlying inflammatory or metabolic processes associated with rheumatic conditions.This capability facilitates early intervention and personalized treat-ment strategies,ultimately contributing to improved patient outcomes and satisfaction.The integration of infrared thermography with advanced image processing algorithms and artificial intelligence further ampli-fies its potential,enabling automated analysis and interpretation of thermal images,thus reducing the dependence on manual interpretation and enhancing the reproducibility and reliability of diagnostic results.In conclusion,infrared thermography represents as a promising tool in the management of rheu-matic diseases,offering a non-invasive,cost-effective,and efficient means for early diagnosis,monito-ring,and therapeutic evaluation of diseases.As technology continues to evolve,the application of infra-red thermography is expected to advance further in rheumatic diseases.

Objective:To investigate the expression level of plasma miR-320c in patients with osteoarthritis(OA), and explore the clinical significance and the role in pathogenesis of OA.Methods:The clinical data and peripheral blood of 30 patients with OA, 30 patients with connective tissue diseases and 30 healthy control individuals were collected.The levels of plasma miR-320c were detected byfluorescentquantitative reverse transcription PCR(qRT-PCR). Correlation analysis was used to explore the correlation of plasma miR-320c level with knee X-ray data and VAS pain score in OA patients.Finally the miR-320c mimic, the miR-320c inhibitor, and the control material were transfected to the chondrocyte HC-a.The proliferative capacity of HC-a chondrocytes was examined at different time points as determined by the CCK-8 assay.Results:The expression level of plasma miR-320c was significantly higher in OA group(3.26±0.55)than that in the connective tissue diseases group(1.62±0.50)and in healthy control group(1.21±0.66)( F=107.66, P<0.001). Plasma miR-320c expression was positively correlated with radiographic grade( r=0.830, P<0.001), and had no correlation with VAS pain score in OA group( P>0.05). Through repeated measurement variance analysis, the time effect, the group effect and the interaction effect between group and time showed statistically significant differences in chondrocyte proliferation between NC mimic group and miR-320c mimic group( Ftime=5256.767, Fgroup=1947.436, Ftime×group=114.314, all P<0.001). The level of proliferation was significantly reduced.Apoptosis rate of chondrocytes was significantly increased in the group transfected with miR-320c( t=7.85, P<0.01). Conclusions:The expression level of plasma miR-320c is significantly higher in osteoarthritis patients and associated with knee radiographic severity grade.Furthermore, over-expression of miR-320c could suppress the proliferation of chondrocytes.Plasma miR-320c might be potential bio-marker for osteoarthritis knee severity assessment, and involves in regulating chondrocyte growth in the pathogenesis of osteoarthritis.

Objective:To study the clinical characteristics and compliance of early-onset gout patients by case-control analysis.Methods:A total of 111 early-onset patients (onset age ≤35 years old) were included as Group A, and 111 non-early-onset patients (onset age >35 years old) with matched disease durationwere included as Group B. The differences ofclinical characteristics, causes of acute gout attack, dairy diet habits, compliance, and misunderstanding of the disease were compared.Results:Compared with the non-early-onsetgoutpatients, the early-onset patients had a higher proportion of obesity (63 cases vs 28 cases), family history (36 cases vs 20 cases) and tophus (39 cases vs 23 cases) and higher level of VAS scores (8.5±1.3 vs 7.6±1.7; χ2=22.988, P<0.01; χ2=5.749, P=0.016; χ2=5.729, P=0.017; t=4.639, P<0.01), lowerproportionof the first metatarsophalangeal joint involvement as the initial joint involvement (45.9%, 51 cases vs 59.4%, 66 cases; χ2=4.066, P=0.044), higher proportion of the ankle involvement as the initial joint involvement (34.2%, 38 cases vs 21.6%, 24 cases; χ2=4.386, P=0.036), higher proportion of alcohol drinkers and high fructose drinkers, which was more likely to relate to alcohol intake, strenuous exercise and high fructose intakeas trigger of the flare ( χ2=6.513, P=0.011; χ2=7.126, P=0.008; χ2=1.978, P=0.160), while the proportion of regular exercisers and on diet in the family was lower ( χ2=22.887, P<0.01; t=-4.917, P<0.01). The proportion of poor diet and medication compliance in Group A was higher than that in Group B(57.7%, 64 cases vs 38.7%, 43 cases; χ2=5.207, P=0.022; χ2=5.867, P=0.015). As for the reason for poor treatment compliance, early-onset gout patients were more worry about the side-effects of drugs than non-early onset patients ( χ2=4.190, P=0.041). There was no significant difference between the two groups in the main misunderstanding of gout. Conclusion:Although early onset gout patients are young, their condition is more serious, and compliance is poorer, this group of patients should be highly valued in clinical diagnosis and treatment.

Objective To investigate the current situation in Chinese rheumatologic physicians' clinical diagnosis and evaluation of Takayasu's arteritis (TA).Methods Nineteen rheumatology experts and three vascular surgery specialists in China were invited to make the nationwide investigation for the first time about the diagnosis and disease activity evaluation of TA in China,through the questionnaire survey on the internet.Weighted average was used to calculate the average scores of corresponding problems.Results Chinese experts mainly adopted 1990 American College of Rheumatology (ACR) classification criteria for clinical diagnosis of TA.In details,symptoms of age,limb claudication and amaurosis,signs including pulselessness or pulse weakening,vascular bruits,increasing bilateral pulse pressure and hypertension and acute phase reactants (APR) were critical to the clinical diagnosis of TA.Besides,noninvasive imaging examinations,such as computed tomography angiography (CTA),magnetic resonance angiography (MRA),vascular ultrasonography,and positron emission tomography (PET) were also of great importance.In the aspect of disease activity assessment,Chinese experts mainly used Kerr scoring tool.APR and noninvasive radiological examinations were considered with vital value.Some TA patients with carotid artery involvement were recommended using vascular ultrasonography,while others with pulmonary artery and thoracic/abdominal aorta trunk involvement were preferred CTA other than MRA.Conclusions APR and noninvasive imaging examinations were thought with great help to make clinical diagnosis and evaluation of TA for Chinese physicians.

Six patients with Neuro-Behcet disease (NBD) were admitted in Beijing Hospital from 2000 to 2014,during the same period 344 NBD cases were reported in the literature.The clinical data of 350 Chinese NBD patients,including the symptoms,signs,laboratory tests,imaging,treatment and prognosis were retrospectively analyzed.The average onset age was 36.7 years old.The average interval time from Behcet disease (BD) to NBD was 5.6 years.NBD often occurred in male,the male/female ratio was 1.94:1.The most common manifestations were oral ulcer 94.9％ (277/292),followed by genital ulcer 69.1％ (215/311) and fever 42.1％ (131/311).The most common symptoms in neurology were limb weakness (36.9％,129/350),headache (34.0％,119/350) and sensory disturbance (21.1％,74/350),followed by bulbar symptoms (11.4％,40/350),pyramidal sign was most often (27.1％,95/350).The central neurology system (CNS) was the major target of NBD,parenchymal CNS was affected most (88.0％,308/350),non-parenchymal CNS was affected less (5.7％,20/350),peripheral neurology system (PNS) was rarely affected (6.9％,24/350).Steroids were the first-line drug for NBD,if it failed,immunosuppressive agents or biologic agents could be used.The most NBD patients had single episodes,32.0％ (49/153) had relapses with remission,7.7％ (27/350) had adverse prognosis.Analysis showed that NBD should be paid more attention.

Objective To investigate the correlation of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 gene single nucleotide polymorphism (SNP) and osteoarthritis (OA) in Beijing.Methods In this case-control study 166 OA patients and 204 normal controls were collected from Beijing.Sorted gene type by SNaPshot technique,and analyzed the difference of allele and genotype frequencies between OA and the controls.The correlation of linkage disequilibrium and haplotype of SNPs with OA was analyzed through Haploview softeware.Results Rs2132824 was the positive site with Bonferroni method after multiple testing correction (x2=0.1 1,P＜0.05),of which allele frequencies had no significant difference between OA and the control (P＞0.05).But in codominant genetic model,rs2132824 CT genotype with OA was inversely proportional to the risk of OA [OR (95％CI) was 0.52 (0.32,0.86),P＜0.05],and TT genotype was directly proportional to the risk of OA [OR(95％CI) was 3.16 (1.55,6.47),P＜0.05],while in recessive genetic model,TT genotype was in direct proportion to the risk of OA [OR (95％CI) was 3.99 (1.99,8.01),P＜0.05].Linkage disequilibrium in SNPs of rs151065,rs229077,rs56153501,rs2830580 and rs58215296 did exist,which made haplotype of rs 151065-rs229077-rs56153501-rs2830580-rs58215296 (G-T-A-C-A) directly proportional to the risk of OA [OR(95％CI) was 1.874(1.019,3.446),P＜0.05].Conclusion ADAMTS-5 gene SNP is associated with OA susceptibility risk in Beijing.Genotype CT of rs2132824 is a low risk factor for OA while TT is a hygh risk factor.Haplotype of G-T-A-C-A is connected with high risk of OA.