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

BACKGROUND:Inflammation,oxidative stress and bacterial infection are the main causes of delayed wound healing in diabetes.In recent years,various inorganic nanomaterials have been widely used in the treatment of skin wound healing due to their antibacterial activities,but their effects on anti-oxidation and anti-inflammation are limited. OBJECTIVE:To investigate the effect of Prussian blue nanoparticles on the wound repair of diabetes in terms of antioxidant,anti-inflammatory and photothermal antibacterial activities. METHODS:Prussian blue nanoparticles were prepared and characterized.(1)In vitro:The biocompatibility of Prussian blue nanoparticles with different concentrations was detected by MTT assay.The cytoprotective effect of Prussian blue nanoparticles and the intracellular reactive oxidative species level were examined under the condition of hydrogen peroxide.The ability of Prussian blue nanoparticles to decompose hydrogen peroxide and superoxide anion radicals was tested;the effect of Prussian blue nanoparticles on lipopolysaccharide-induced macrophage inflammation was investigated.The photothermal antibacterial activity of Prussian blue nanoparticles was detected by the plate colony counting method.(2)In vivo:ICR mice were intraperitoneally injected with streptozotocin to establish a diabetes mouse model.After the model was successfully established,a 6 mm wound was created on the back with a hole punch.There were the control group(no treatment),the Prussian blue group and the Prussian blue with light group.The wound healing and histomorphological changes were observed. RESULTS AND CONCLUSION:(1)In vitro:Prussian blue nanoparticles in 25-200 μg/mL were non-toxic to cells.Prussian blue nanoparticles had the extremely strong antioxidant capacity and mitigated the intracellular reactive oxidative species at a high oxidative stress environment,resulting in a pronounced cytoprotective effect.The Prussian blue nanoparticles not only exhibited hydrogen peroxide degradation activity but also showed strong superoxide scavenging ability.Prussian blue nanoparticles also displayed significant anti-inflammatory activity and extremely strong antibacterial ability after light irradiation.(2)In vivo:After 14 days,the wound sizes of the Prussian blue group and Prussian blue with light group were significantly reduced,and the healing speed of Prussian blue with light group was the fastest.Hematoxylin-eosin and Masson staining showed a lot of granulation tissue formation and collagen deposition in the Prussian blue group and the Prussian blue with light group,of which the Prussian blue with light group was the most.Immunofluorescence staining displayed that,compared with the control group,the expressions of α-SMA and CD31 were increased significantly in Prussian blue group and Prussian blue with light group(P<0.05),but F4/80 expression was decreased significantly in Prussian blue group and Prussian blue with light group(P<0.05),indicating more obvious improvement in the Prussian blue with light group.(3)These results showed that Prussian blue nanoparticles could promote the skin wound healing of the diabetes mouse model by exerting anti-inflammatory,antioxidant and antibacterial effects.

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

Objective To observe the clinical effect and safety of recombinant human interferon-α2b(rhIFN-α2b)combined with 5-aminolaevulinic acid photodynamic therapy(ALA-PDT)in the treatment of patients with cervical intraepithelial lesions and human papilloma virus(HPV)infection.Methods The clinical data of patients with cervical intraepithelial lesions and HPV infection were analyzed retrospectively.The patients were divided into control group and treatment group according to cohort method.The control group was treated with rhIFN-α2b gel at posterior fornix,qd.On this basis,the treatment group was treated with ALA-PDT,namely applying 5％ALA temperature-sensitive gel prepared by 118 mg of ketone valerate hydrochloride powder for external use on vaginal surface,combined with photodynamic therapy,once a week.The clinical efficacy,time to recovery from clinical symptoms,recurrence rate,changes in cytokines[interleukin-6(IL-6),interleukin-8(IL-8)and interferon-γ(IFN-γ)]and immune function[T cell subsets CD3+,CD4+,CD8+and CD4+/CD8+],and safety were compared between the two groups.Results There were 98 cases in treatment group and 100 cases in control group.The total effective rates in treatment group and control group were 93.88％and 83.00％,with statistically significant difference(P＜0.05).The relief time of lower abdominal pain in treatment group and control group were(3.65±0.52)and(5.26±0.65)d;the time to recovery from abnormal vaginal discharge were(5.77±0.83)and(7.16±0.92)d;the time to recovery from irregular vaginal bleeding were(4.82±0.62)and(6.94±0.77)d;HPV clearance rates were 58.16％and 42.00％;IL-6 levels were(0.16±0.09)and(0.23±0.05)mg·L-1;IL-8 levels were(0.47±0.05)and(0.66±0.07)mg·L-1;IFN-γ levels were(10.07±0.98)and(7.24±0.65)ng·mL-1;CD3+were(71.06±8.29)％and(61.36±6.88)％;CD4+were(48.25±5.94)％and(42.25±5.13)％;CD8+were(20.37±2.42)％and(24.69±2.51)％;CD4+/CD8+were 2.11±0.27 and 1.36±0.16;the differences were all statistically significant(all P＜0.05).Recurrence rates in treatment group and control group were 5.10％and 14.00％,with statistically significant difference(P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 26.53％and 21.00％,without statistically significant difference(P＞0.05).Conclusion The combined treatment of rhIFN-α2b and ALA-PDT is effective for patients with cervical intraepithelial lesions and HPV infection.It has obvious advantages in improving immunity,relieving inflammatory response and reducing recurrence rate,with good safety.

AIM To study the protective effects and mechanism of pueraria isoflavones on myocardial injury in ovariectomized rats.METHODS Thirty-six rats were randomly divided into the sham operation group,the model group,the estradiol valerate group(0.1 mg/kg)and the low,medium and high dose pueraria isoflavones groups(55,110,220 mg/kg).In contrast to the rats of the sham operation group having their small pieces of adipose tissue removal around the ovaries,rats of the other groups had their bilateral ovaries excised,followed by the 16-week corresponding oral drug administration 2 weeks later at a once daily frequency for,6 days a week.At the end of the 16th week,the rats had their hemodynamics[systolic pressure(SBP),diastolic pressure(DBP),mean pressure(MBP),left ventricular systolic pressure(LVSP),left ventricular diastolic pressure(LVMP),and the maximum rate of increase and decrease of left ventricular pressure during isovolumic contraction(±dp/dtmax)]detected by PowerLab;their cardiac pathological changes observed by HE staining;their levels of creatine kinase(CK),lactate dehydrogenase(LDH),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)and glucose(Glu)in plasma detected by biochemical analyzer;their myocardial level of adenosine triphosphate(ATP)detected by colorimetry;their mRNA expressions of glucose transporter 4(GLUT4),lactate dehydrogenase A(LDHA),carnitine palmitoyl transferase-1(CPT-1α),acyl coenzyme A carboxylase(ACC),liver kinase B1(LKB1),adenylate-activated protein kinase(AMPK)and peroxisome proliferator-activated receptor γ coactivator factor 1α(PGC-1α)detected by RT-qPCR;and their myocardial expressions of energy metabolism related proteins LKB1,p-AMPK/AMPK and PGC-1α detected by Western blot.RESULTS Compared with the model group,the pueraria isoflavones groups displayed decreased levels of SBP,DBP,MBP,LVSP,LVMP(P＜0.05,P＜0.01);increased-dp/dtmax(P＜0.05,P＜0.01);improved myocardial fibrinolysis,gap widening and inflammatory infiltration caused by ovariectomy;decreased activities of LDH and CK(P＜0.05);increased myocardial ATP level(P＜0.05,P＜0.01);decreased levels of TC,TG,LDL-C and Glu(P＜0.05,P＜0.01);increased HDL-C level(P＜0.05,P＜0.01);increased myocardial mRNA expressions of GLUT4,LDHA,CPT-1α,ACC,LKB1,AMPK and PGC-1α(P＜0.05,P＜0.01);and increased protein expressions of myocardial LKB1,p-AMPK/AMPK and PGC-1α(P＜0.05,P＜0.01).CONCLUSION Pueraria isoflavones are protective to myocardial injury in ovariectomized rats,and the mechanism may lie in the improvement of energy metabolism-related myocardial proteins via LKB1/AMPK/PGC-1α signaling pathway.

AIM To study endophytic fungi from Scutellaria baicalensis Georgi.and the enzyme inhibitory activities of their secondary metabolites.METHODS Six different media were used to isolate and purify endophytic fungi from S.baicalensis by tissue homogenate method.The activities of secondary metabolites were evaluated by targeting different enzymes.The highly active strains were identified by molecular biology combined with morphology,and the highly active chemical components were tracked and separated by modern chromatographic separation technology.RESULTS Sixty-four endophytic fungal strains were isolated from S.baicalensis,and one hundred and twenty-eight secondary metabolites were obtained by fermentation.The samples with certain inhibitory activities against adenosine deaminase(ADA),β-lactamase and tyrosinase(TYR)accounted for 14.06%,3.91%and 18.75%,respectively.Strain HTS-23-2 showed high TYR inhibitory activity,and 99%homology with Aspergillus flavus by molecular identification.One compound was isolated from the fermentation samples and identified as kojic acid.CONCLUSION S.baicalensis harbors a rich diversity of endophytic fungi,which serve as a valuable resource for active substances.

Objective:Analyze the medical reimbursement rate and influencing factors under the DIP payment method to refine the DIP payment policy,promote the optimization of internal operations in medical institutions,and ensure reasonable compensation.Methods:Based on the 2022 DIP fund settlement data from 196 medical institutions in City A,the study used multiple linear regression to analyze the factors affecting medical reimbursement rate and conducted a heterogeneity analysis for medical institutions of different levels.Results:The medical reimbursement rate for medical institutions in City A in 2022 was 103.32%.Medical institutions with lower CMI standardized inpatient costs,lower rates of deviation cases,tertiary care institutions,lower proportion of level-four surgeries,and lower ratios of resident to employee medical insurance cases have higher medical reimbursement rate(P<0.05).Heterogeneity analysis reveals that therates of deviation cases,the proportion of primary care diseases,the ratio of resident to employee medical insurance cases,and the low-standard admission rate have different impacts on medical institutions of different levels.Conclusion:Medical insurance departments should improve policies for primary care diseases,dynamically adjust disease catalogs and payment standards,optimize funding levels and institutional coefficients,and increase penalties for violations to ensure effective use of funds.Medical institutions need to strengthen their understanding of policies,focus on refined internal management,promote standardized and rational diagnosis and treatment through performance assessment transformation,and leverage their own advantages in medical services to reasonably increase the medical reimbursement rate.

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Dalbergia ; Myocardial Ischemia ; Metabolomics ; Heart ; Heart Injuries ; Creatine Kinase, MB Form

Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.
Artificial Intelligence ; Enzyme Inhibitors/pharmacology* ; High-Throughput Screening Assays ; Molecular Docking Simulation

Two new ursane triterpenoids along with twelve known compounds were isolated from 80% ethanol extract of Agastache rugosa (Fisch. et. Mey.) O. Kuntze by using silica gel column, MCI column, ODS column and HPLC. The structures of the new compounds were identified as 2α,3α-dihydroxy-24-nor-urs-4(23),12(13)-dien-28-oic acid (1) and 2α,3α-dihydroxy-24-nor-urs-4(23),12(13),20(30) -trien-28-oic acid (2) by HR-ESI-MS, NMR and ECD spectral data, named agasursacid A and agasursacid B. In addition, compounds 3, 4, 6, 8 showed anti-coxsackievirus B3 (CVB3) activities with a IC₅₀ as 4.77, 1.59, 11.11 and 25.87 μmol·L^-1, resepectively.