This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Allergen-specific immunotherapy（AIT） remains the only therapeutic approach with the potential to modify the natural course of allergic rhinitis（AR）. Nevertheless, considerable inter-individual variability exists in patients'responses to AIT. To facilitate more reliable assessment of treatment efficacy, the China Rhinopathy Research Cooperation Group（CRRCG） convened young and middle-aged nasal experts in China to formulate the present consensus. The recommended subjective outcome measures for AIT comprise symptom scores, medication scores, combined symptom and medication scores, quality-of-life assessments, evaluation of disease control, and assessment of comorbidities. Objective indicators may supplement these measures. Currently available objective approaches include skin prick testing, nasal provocation testing, and allergen exposure chambers. However, these methods remain constrained by practical limitations and are not yet appropriate for routine implementation in clinical efficacy evaluation. In addition, several biomarkers, including sIgE and the sIgE/tIgE ratio, sIgG4, serum IgE-blocking activity, IgA, cytokines and chemokines, as well as immune cell surface molecules and their functional activity, have been shown to have associations with AIT outcomes. While these biomarkers may complement subjective assessments, they are subject to significant limitations. Consequently, large-scale multicenter trials and real-world evidence are required to strengthen the evidence base. The present consensus underscores the necessity of integrating patients'subjective experiences with objective testing throughout the treatment process, thereby providing a more comprehensive and accurate framework for efficacy evaluation. Looking forward, future investigations should prioritize the incorporation of multi-omics data and artificial intelligence methodologies, which hold promise for overcoming current limitations in assessment strategies and for advancing both the standardization and personalization of AIT.
Humans ; Allergens/immunology* ; China ; Consensus ; Desensitization, Immunologic ; Immunoglobulin E ; Quality of Life ; Rhinitis, Allergic/therapy* ; Treatment Outcome ; East Asian People

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Objective:To analyze the mutant spectrum of clonal hematopoiesis of indeterminate potential(CHIP)related mutations and clinical characteristics and to explore the correlation and the possible mechanism between CHIP-related mutations and cardio-cerebrovasculars events(CCEs)in patients with myeloproliferative neoplasms(MPNs).Methods:The clinical data and next-generation sequencing results of 73 MPN patients in Beijing Anzhen Hospital from August 2019 to July 2022 were retrospectively analyzed.Statistical analyses were conducted by multivariate logistic regression for the effects of CHIP-related mutations and inflammatory cytokines on CCEs for MPNs patients.Results:Fifty-five cases of MPN(75.3％)showed positive in CHIP-related genes.There was no significant difference in variant allele frequency of CHIP-related gene between essential thrombocythemia(ET)and polycythemia vera(PV).CHIP-related gene mutations were mainly single gene mutations,with mutation rate from high to low as JAK2V617F(63.0％,46/73),ASXL1(16.4％,12/73),TET2(11.0％,8/73),DNMT3A(9.6％,7/73),SRSF2(6.9％,5/73),SF3B1(4.1％,3/73),TP53(1.4％,1/73)and PPM1D(1.4％,1/73).The mutation rate of CHIP-related genes in MPN patients＞60 years old was significantly higher than that in the patients ≤ 60 years old[91.7％(33/36)vs 59.5％(22/37)].CCEs occurred in 27 MPNs patients(37.0％,MPNs/CCEs),and 5 had recurrent CCEs,all of which were arterial events.Age(62.8±12.8 years vs 53.9±15.8 years,P=0.015),IL-1β level(17.7±26.0 vs 4.3±8.6,P=0.012),IL-8 level(360.7±598.6 vs 108.3±317.0,P=0.045),the proportion of the patients with thrombosis history(29.6％vs 2.2％,P=0.020),and the detection rate of CHIP-related mutations(88.9％vs 67.4％,P=0.040)in the group with CCEs were higher than those in the group without CCEs.Multivariate Logistic regression analysis showed that age(OR=0.917,95％CI:0.843-0.999,P=0.047),thrombosis history(OR=34.148,95％CI·2.392-487.535,P=0.009),any CHIP-related mutations(OR=16.065,95％CI·1.217-212.024,P=0.035),and elevated levelofIL-1β(OR=0.929,95％CI:0.870-0.992,P=0.027)were independent risk factors for MPNs/CCEs.CHIP-related gene mutations were not associated with CCEs in MPN patients,but DNMT3A(OR=88.717,95％CI:2.690-292.482,P=0.012)and ASXL1(OR=7.941,95％CI:1.045-60.353,P=0.045)were independent risk factors for CCEs in PV.Conclusion:There is a higher mutation rate of CHIP-related genes in MPN patients,especially those over 60 years old.Older age,thrombosis history,CHIP-related mutations and IL-1βelevated levels are independent risk factors for CCEs in MPN.DNMT3A and ASXL1 mutations are independent risk factors for CCEs in PV patients.CHIP-related gene mutations and inflammatory cytokine IL-1 β elevated levels may be the novel risk factors for CCEs in MPN.

Macrophages, existed in almost all organs of the body, are responsible for detecting tissue injury, pathogens, playing a key role in host defense against a variety of invading pathogens triggering inflammatory responses. Emerging evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification, which is responsible for normal immune responses. However, numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation, mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal expression. Notably, E3 ubiquitin ligases, responsible for recognizing the substrates, are key enzymes in the ubiquitin-proteasome system (UPS) composed of ubiquitin (Ub), ubiquitin-activating E1 enzymes, ubiquitin-conjugating E2 enzymes, E3 ubiquitin ligases, 26S proteasome, and deubiquitinating enzymes. Intriguingly, several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation, including Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and the receptor for advanced glycation end products (RAGE). Herein, we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation, as well as the inhibitors and agonists targeting E3 ligases in macrophage-mediated inflammation, providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.

This study aimed to investigate the influence of anti-cross-reactive carbohydrate determinant IgE antibodies (anti-CCD IgE) on the detection of allergen-specific IgE (sIgE) antibodies, as well as the application value of anti-CCD IgE adsorbents in detecting allergen sIgE. In this cross-sectional study, a total of 2 636 test samples from patients who received treatment in West China Hospital of Sichuan University and tested allergen sIgE using the western blot method from October 2020 to May 2021 were analyzed. In these samples, 709 samples tested postive of allergen sIgE. 46 stochastic venous serum samples that tested positive in both sIgE and anti-CCD IgE and 1 serum sample that tested positive in sIgE but negative in anti-CCD IgE were collected. These samples were processed by anti-CCD IgE adsorbents, followed by allergen sIgE detection. The difference between the two detection results before and after adsorption was analyzed. The allergen test results showed that the positive rate of anti-CCD IgE in samples was 2.6% (69/2 636) during the period of sample collection. After treatment with anti-CCD IgE adsorbents, the top three allergen-sIgE of the positive rate changed from tree combination 2 (willow/poplar/elm), common ragweed and peanut to dust mite combination, cockroach and crab. The positive anti-CCD IgE results of 46 samples all turned negative and the total positive sIgE antibody dropped by 62.8%; the positive rate of sIgE antibodies with the class result ≥2 significantly decreased after treatment with anti-CCD IgE adsorbents, especially the positive rate of common ragweed dropped by 96.2%. The results of positive samples showed that multiple sIgE antibodies declined by different ranges, involving up to 11 antibodies with a maximum decline of 4 classes. Strongly positive sIgE antibodies (the class result ≥4) also had a high conversion rate of negative (25.0%-100%). The positive sIgE antibodies in about 60% of the samples decreased by more than 2, and the sIgE antibodies in 17.4% of the samples turned completely negative. There was no change in the allergen sIgE detection results of the sample with negative anti-CCD IgE after treatment. In conclusion, sIgE antibodies including targeting common ragweed, humulus, tree combination 2 (willow/poplar/elm), etc. are susceptible to false positives caused by anti-CCD IgE. Treatment of samples with anti-CCD IgE adsorbents can significantly reduce the risk of false positives caused by anti-CCD IgE. It is necessary to pretreat samples that were anti-CCD IgE positive with anti-CCD IgE adsorbents, which can make laboratory results more accurate and provide a reference for diagnosis and prevention of allergic diseases.

Objective To explore the role of ATM/hnRNPK signaling in the adriamycin resistance of acute myeloid leukemia.Methods Expression of ATM was examined in the adriamycin resistant and sensitive leukemia cell strains with Western blot.ATM expression was down-regulated by RNAi and ATM inhibitor in the adriamycin resist-ant cell strains.Expression level of hnRNPK and LC3Ⅰ/Ⅱ was detected by Western blot and adriamycin sensitivity was measured by CCK8 assay before and after modulation of ATM expression.Results ATM was overex-pressed in adriamycin resistant leukemia cell strains.The decreased expression of ATM restored the sensitivity to adriamycin.Expression level of LC3Ⅱ and hnRNPK was consistent with the modulation of ATM expression.Conclusions The ATM/hnRNPK signaling pathway may play a role in the occurrence of adriamycin resistance in acute myeloid leukemia by regulating autophagy.

Objective To explore the cut-off value of three dimensional(3D)vena contracta area(VCA)in diagnosing severe tricuspid regrugitation(TR)under different etiologies and its accuracy and practicality in clinical application.Methods From Mar 2019 to May 2021,ninety-two patients with confirmed TR underwent two dimensional(2D)and 3D transthoracic echocardiography.The correlation and consistency between 3D VCA 3D calculated based on the proximal isokinetic surface area(PISA)effective regurgitant orifice area(EROA)was calculated.Comprehensive 2D multi-parameter method was used as a reference method to calculate the cut-off value of the diagnosis of severe TR.Results A total of 85 patients were ultimately included.3D VCA and 3D PISA EROA had similar and acceptable correlations in both primary TR and secondary TR(primary TR:r=0.831,P<0.01;secondary TR:r=0.806,P<0.01).Bland-Altman analysis showed that 3D VCA overestimated TR compared with 3D PISA EROA(62%overestimated in the total patient population,51%overestimated in primary TR,and 74%overestimated in secondary TR).In secondary TR,the cut-off value of 3D VCA for diagnosing severe TR was 0.45 cm2(sensitivity 89%,specificity 82%);combining clinical symptoms,positive 2D PISA EROA results and 3D VCA results for severe TR,the chi-square value was higher than those only included clinical symptoms or incorporated clinical symptoms and positive 2D PISA EROA results(42.168 vs.26.059 and 16.759,P<0.01).Conclusion 3D VCA would overestimate TR,and had high and incremental diagnostic value for evaluating severe TR in secondary TR.

Objective To investigate anxious and depressive emotions in patients underwent cervical cancer surgery and to analyze its influencing factors.Methods A total of 304 patients who underwent primary cervical cancer surgery in Obstetrics and Gynecology Hospital,Fudan University from Oct 2018 to Jun 2021,were recruited to evaluate the clinical effect based on cervical cancer-patient reported outcome 137 scale(CC-PRO137 scale).This study focused on dimensions of depressive and anxious emotions within this scale and explored their influencing factors.Results The average scores of their depressive and anxious emotions within half a year after surgery were 4.141±0.798 and 4.020±0.616,respectively;and the average scores of depressive and anxious emotions more than one year after surgery were 4.250±0.802 and 4.097±0.613,respectively.By using statistical methods including analysis of variance and t test,it was found that there were statistically significant differences in the scores of depression and anxiety among cervical cancer patients under different postoperative adjuvant treatments and at different postoperative time points(P<0.05).However,there were no statistically significant differences in the scores of depression and anxiety among patients with different ages,surgical methods,and clinical stages of cervical cancer(P>0.05).Conclusion Patients underwent cervical cancer surgery may suffer varying degree of depressive and anxious emotions,and the main influencing factors are different adjuvant treatments and the length of time for postsurgical recovery.Medical practitioners should strengthen comfort and care for patients with cervical cancer,especially those who receive chemotherapy and radiotherapy treatments and are in the primary stage after the surgery.Formulating positive intervention measures can effectively reduce the psychological pain of patients and safeguard their physical and mental health.