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

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

ObjectiveTo investigate the mechanism of Renshen Guben oral liquids（RGOL） in treatment of mice with renal fibrosis based on metabolomics and network pharmacology. MethodC57BL/6 mice were randomly divided into control group， model group and RGOL group， 12 mice in each group. Except for the control group， mice in the other groups were induced into unilateral ureteral obstruction（UUO） model by UUO. After preparation of the model， an aqueous solution of 4.2 g·kg^-1 extract powder was administered by gavage to RGOL group for 14 d， and an equal amount of distilled water was administered by gavage to the control and model groups. After the last administration on the 14^th day， urine was collected and detected by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QQQ-MS/MS） with 0.1% formic acid aqueous solution as mobile phase A， and acetonitrile-isopropanol（70∶30） as mobile phase B for gradient elution（0-1 min， 5%B； 1-5 min， 5%-30%B； 5-9 min， 30%-50%B； 9-11 min， 50%-78%B； 11-13.5 min， 78%-95%B； 13.5-14 min， 95%-100%B； 14-16 min， 100%B； 16-16.1 min， 100%-5%B； 16.1-18 min， 5%B）， column temperature of 40 ℃， flow rate of 0.4 mL·min^-1， electrospray ionization（ESI）， collection range of m/z 50-900. Through network pharmacology， the targets of components in RGOL and the targets of renal fibrosis were analyzed interactively， and the key components and key targets were screened by network topology analysis， and DAVID platform was used to predict the signaling pathways of RGOL for the treatment of renal fibrosis. ResultA total of 7 differential metabolites involving 8 metabolic pathways were identified in RGOL for the treatment of renal fibrosis. The network pharmacology revealed that 36 key components in RGOL were related to 7 differential metabolites， mainly ginsenosides， notoginsenosides and nucleotides. Based on the herbs-components-targets-pathways network， a total of 23 key targets related to the treatment of renal fibrosis by RGOL were highlighted， which together with the differential metabolites were involved in linoleic acid metabolism， arginine biosynthesis， tricarboxylic acid cycle（TCA）， arginine and proline metabolism and other pathways. ConclusionBased on metabolomics and network pharmacology， this study preliminarily identified 7 differential metabolites， 36 potential pharmacodynamic components and 23 key targets and 4 key pathways in RGOL for the treatment of renal fibrosis， providing an experimental basis for the clinical application and mechanism study of this preparation.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

Over the past decade, traditional Chinese medicine (TCM) has widely embraced systems biology and its various data integration approaches to promote its modernization. Thus, integrative pharmacology-based traditional Chinese medicine (TCMIP) was proposed as a paradigm shift in TCM. This review focuses on the presentation of this novel concept and the main research contents, methodologies and applications of TCMIP. First, TCMIP is an interdisciplinary science that can establish qualitative and quantitative pharmacokinetics-pharmacodynamics (PK-PD) correlations through the integration of knowledge from multiple disciplines and techniques and from different PK-PD processes

Pancreatic cancer has poor prognosis and lymph node metastasis is a poor prognostic factor in patients with resectable pancreatic cancer. The metastatic prevalence of para-aortic lymph node (PALN) ranges from 9.1% to 26.5% and it is listed as the distant metastatic group in pancreatic cancer. Nevertheless, it is controversial whether PALN metastasis is the contraindication of surgery in resectable pancreatic cancer for the shortage of level Ⅰ evidence.This study concluded that PALN metastasis indicated poor prognosis in patients with pancreatic cancer, but some patients with PALN metastases could benefit from surgery and their survival could be much improved after the combination of surgery and adjuvant therapy. Therefore, it is not wise to refuse surgery for all pancreatic cancer patients with PALN metastasis and the clinicians can cautiously choose the patients to do surgery. Besides, there are mainly retrospective studies rather than prospective and multicenter studies to explore the prognosis of pancreatic cancer patients with PALN metastasis. Thus, more prospective and multicenter studies are needed to decide whether PALN metastasis is an independent prognostic factor in patients with resectable pancreatic cancer.

Objective: To study the value of olfactory cleft scores through computed tomography (CT) in predicting the oral glucocorticoids (GC) sensitivity in chronic rhinosinusitis with nasal polyps. Methods: Fourty-seven consecutive patients with CRSwNP from the Fifth Affiliated Hospital of Sun Yat-sen University between January and March of 2018 were recruited in this prospective, single-blinded study. There were 28 males and 19 females, with age ranging from 17 to 66 years old. After a course of oral prednisone (30 mg/d for 14 d), these patients were subsequently classified into objectively GC-sensitive and -insensitive subgroup according to the change in nasal polyp size score, or subjectively GC-sensitive and -insensitive subgroup according to the change in total nasal symptom score. The following parameters were compared between GC-sensitive and -insensitve subgroups: Lund-Mackay scores, olfactory cleft scores, and blood eosinophil counts and ratio. T test and χ² test were used. Multivariate Logistic regression analysis was used for factor prediction and receiver operating characteristic (ROC) curve was used to analyze the predictive ability of those factors. Results: There were 53.2% (25/47) and 61.7% (29/47) of patients objectively and subjectively sensitive to GC therapy, respectively. All data conformed to normal distribution. The olfactory cleft score and the blood eosinophil counts and ratio in objectively GC-sensitive subgroup were significantly higher than those in objectively GC-insensitive subgroup (3.6±1.0 vs 2.2±1.4, (404.4±200.3)/μl vs (209.5±233.1)/μl, (5.25±2.59)% vs (3.17±3.46)%, t value was 3.98, 3.08, respectively, χ²=2.35, all P<0.05). The cleft score, the blood eosinophil counts and ratio also showed the same trend in subjectively GC-sensitive and -insensitive subgroup (3.6±1.0 vs 1.9±1.3, (401.4±213.6)/μl vs (171.1±200.2)/μl, (5.39±2.76)% vs (2.48±2.99)%, t value was 5.05, 3.68, respectively, χ²=3.40, all P<0.05). Multivariate Logistic regression revealed that olfactory cleft score was an independent risk factor for objective or subjective GC-sensitivity (OR=2.882, 95%CI: 1.301-6.384; OR=2.508, 95%CI: 1.248-5.039). The olfactory cleft score exhibited comparable accuracy with the blood eosinophil ratio as predictor of objective and subjective GC-sensitivity (Area under curve of olfactory cleft score was 0.775, 0.829, respectively). An olfactory cleft score of 3.5 could act as a reliable indicator for predicting the clinical response to GC therapy in CRSwNP. Conclusion Olfactory cleft score through CT scan has the potential value in predicting GC-sensitivity in CRSwNP patients.

Purpose To compare the characteristics of targeted ultrasound contrast agents of ovarian carcinoma xenograft tumor at different stages with SonoVue serving as the contract, and to explore the application value of targeted ultrasound contrast agents in diagnosis of ovarian carcinoma. Materials and Methods Fifty BALB/cNude nude mice were randomly divided into 5 groups with 10 in each group to establish subcutaneous xenograft tumor model of ovarian carcinoma. According to different inoculation time (14, 21, 28, 35, 42 d), 5 groups of nude mice underwent common contrast-enhanced ultrasound (MBc) and targeted ultrasound contrast (MBt) examination. The peak intensity (PI) and time to peak (TTP) of xenograft tumors were calculated by time-signal intensity curves, and their angiographic features were dynamically observed. Results PI in MBt group was higher than that in MBc group at different times, the difference of which was all statistically significant (P<0.05); TTP was shorter than that of MBc group, the difference between 14, 21 and 28 d was statistically significant (P<0.05); TIC curve was steeper at the early stage of inoculation. The difference between PI and TTP in MBt group was statistically significant (P<0.05). The difference of PI between 14 and 21 d, 21 and 28 d, 28 and 35 d were all statistically significant (P<0.01); differences of TTP between 14 and 21 d, 28 and 35 d were all statistically significant (P<0.01); the difference of PI and TTP compared within MBc group had no statistical significance (P>0.05). Conclusion In the early stage of inoculation, the contrast parameters PI and TTP carrying MMP-2 antibody-targeted ultrasound contrast agents are more advantageous than sonovue, which is helpful for the early diagnosis of ovarian carcinoma.

PURPOSE: MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS: Twenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA. RESULTS: After 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10+CD4+ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups. CONCLUSIONS: Our findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.
Biomarkers ; Blotting, Western ; Cell Differentiation ; Child* ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Immunotherapy* ; Interleukin-10 ; Interleukin-5 ; MicroRNAs ; Polymerase Chain Reaction ; Reverse Transcription ; Rhinitis* ; RNA, Messenger ; Sublingual Immunotherapy ; T-Lymphocytes ; TNF Receptor-Associated Factor 6

OBJECTIVE: The aim of this study is to investigate the expression of phosphofructokinase 1 and it's enzyme activity in nasopharyngeal carcinoma biopsy samples. METHOD: Sixty-one biopsy samples were detected, including 41 tissues from patients with nasopharyngeal carcinoma as experimental group and 20 tissues from patients with chronic nasopharyngitis as control group. Phosphofructokinase 1 protein was detected by Western blot and it's enzyme activity was detected. RESULT: It was observed that the expression levels of phosphofructokinase 1 protein and it's enzyme activities in the experimental group were higher than that in the control group (P < 0.01). In the experimental group, the expression levels of phosphofructokinase 1 protein and it's enzyme activities in patients with lymph node metastasis were higher than that in patients without lymph node metastasis (P < 0.01). CONCLUSION Phosphofructokinase 1 may be a marker in occurrence and metastasis of nasopharyngeal carcinoma.
Biomarkers, Tumor ; metabolism ; Biopsy ; Carcinoma ; Case-Control Studies ; Humans ; Lymphatic Metastasis ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; enzymology ; pathology ; Nasopharyngitis ; Phosphofructokinase-1 ; metabolism