Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

A UHPLC-Q-Orbitrap/MS method was developed to identify the related substances in apixaban tablets. Complete separation was accomplished with a Waters Xbridge C18 (250 mm×4.6 mm, 5 μm) column by linear gradient elution using a mobile phase consisting of 30 mmol/L ammonium acetate buffer solution (pH 4.50) and acetonitrile. The related substances were successfully characterized through the accurate mass and elemental composition of the parent ions and their product ions determined by electrospray positive ionization high-resolution Q-Orbitrap/MS methods. Under the established analytical condition, apixaban and its related substances were well separated, and 30 related substances were detected and identified by hyphenated techniques in apixaban tablets and their stressed samples. Among them, 11 were known impurities and the rest 19 were unknown related substances identified for the first time in this study. The results obtained are valuable for apixaban manufacturing process optimization and quality control.

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

Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Objective To investigate the alleviation of Nippostrongylus brasiliensis infection on dextran sulfate sodium salt (DSS)-induced ulcerative colitis in mice, and to explore the underlying mechanism. Methods Thirty male C57BL/6J mice of the SPF grade, each weighing approximately 25 g, were randomly divided into three groups, including the blank control group (NC group), DSS modeling group (DSS group), and N. brasiliensis treatment group (Nb + DSS group), of 10 mice in each group. Mice in the DSS group were orally administered with 3.5% DSS daily since day 1 (D0) for 6 successive days, and given normal drinking water since D6, and animals in the Nb + DSS group were subcutaneously injected with the third-stage larvae of N. brasiliensis at a dose of 500 larvae per mice 5 days prior to D0, followed by oral administration with 3.5% DSS daily since D0 for 6 successive days and normal drinking water since D6, while mice in the NC group were given normal drinking water. Mouse body weight and stool were observed and the disease activity index (DAI) was scored in each group during the study period. All mice were sacrificed on D9. The mouse colon length was measured, and mouse colon specimens were subjected to hematoxylin-eosin (HE) staining and histopathological scoring. In addition, the mRNA and protein expression of interleukin (IL)-1β and IL-10 was quantified in mouse colon specimens using quantitative fluorescent real-time PCR (qPCR) assay and enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expression of mucosal repair-associated molecules zonula occludens-1 (ZO-1), mucin 2 (MUC2) and claudin-1 was detected in mouse colon specimens using qPCR assay and immunofluorescence assay. Results The mice body weights, DAI scores and colon lengths were (26.26 ± 1.93), (22.39 ± 1.65), (25.00 ± 1.58) g (F = 8.06, P < 0.01); (1.89 ± 0.34), (0.47 ± 0.39), 0 points (F = 57.61, P < 0.000 1); and (42.50 ± 5.75), (56.20 ± 5.96) mm and (61.17 ± 7.88) mm (F = 13.72, P < 0.001) in the NC, DSS and Nb + DSS groups on D9, respectively, and elevated mouse body weight (P < 0.05), reduced DAI score (P < 0.000 1) and increased colon length (P < 0.01) were observed in the Nb + DSS group relative to the DSS group on D9. Pathological examinations showed that the colonic crypts were relatively intact and the inflammatory cell infiltration was lower in the mouse colon specimens in the Nb + DSS group than in DSS the group. There was a significant difference in the histopathological scores of mouse colon specimens among the NC group (0 point), the DSS group [(2.00 ± 1.22) points] and the Nb + DSS group [(0.20 ± 0.45) points] (F = 10.71, P < 0.01), respectively, and the histopathological score of mouse colon specimens was significantly higher in the DSS group than in the NC and Nb + DSS groups (both P values < 0.01). qPCR assay quantified that the relative IL-10 and IL-1β mRNA expression was 1.25 ± 0.08, 0.44 ± 0.14 and 1.30 ± 0.45 (F = 10.66, P < 0.01), and 0.22 ± 0.13, 1.14 ± 0.31 and 0.41 ± 0.19 (F = 16.89, P < 0.001) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and higher IL-10 mRNA expression and lower IL-1β mRNA expression were found in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.01). The relative MUC2, claudin-1 and ZO-1 mRNA expression was 0.87 ± 0.25, 0.34 ± 0.26 and 4.21 ± 0.55 (F = 121.60, P < 0.000 1), 1.05 ± 0.41, 0.16 ± 0.09 and 0.22 ± 0.11 (F = 14.00, P < 0.01), and 1.03 ± 0.10, 0.60 ± 0.11 and 1.64 ± 0.28 (F = 32.16, P < 0.000 1) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and significantly higher MUC2 and ZO-1 mRNA expression was quantified in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). The mean fluorescence intensities of ZO-1 and claudin-1 were 17.18 ± 2.08, 12.38 ± 1.21 and 18.06 ± 2.59 (F = 8.95, P < 0.01) and 13.50 ± 1.63, 9.66 ± 2.03 and 13.61 ± 0.97 (F = 6.96, P < 0.05) in mouse colon specimens in the NC, DSS and Nb + DSS groups, respectively, and the mean fluorescence intensities of ZO-1 and claudin-1 were significantly greater in mouse colon specimens in the Nb + DSS group than in the DSS group (both P values < 0.05). Conclusion N. brasiliensis infection may remarkably alleviate DSS-induced ulcerative colitis in mice through promoting expression of anti-inflammatory cytokines, inhibiting expression of pro-inflammatory cytokines and facilitating mucosal repair in colon tissues.

Objective To compare the effects of ginsenosides Rg1 and Rb1 on depression-and anxiety-like behaviors in chronic unpredictable stress-induced rats.Methods Seventy male SPF grade SD rats were tested for sugar and water preference after 5 days of adaptation and divided into seven groups according to their preference index:a control group,model group,fluoxetine hydrochloride group,ginsenoside Rg1 24 mg/kg group,ginsenoside Rg1 48 mg/kg group,ginsenoside Rb1 33 mg/kg group,and ginsenoside Rb1 67 mg/kg group.All rats,except for the control group,were subjected randomly to one or two different stimulating factors every day for a total of 35 days.On the 36th day,behavioral experiments including sugar and water preference,open field,novel environment feeding inhibition,elevated cross maze,and forced swimming experiments were conducted to investigate the anti-depression and anti-anxiety effects of the treatments.Serum and hippocampal levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α and serum corticosterone were measured by enzyme-linked immunosorbent assay.Results Compared with the model group,ginsenoside Rg1 and Rb1 significantly increased sucrose consumption in the sucrose preference test and decreased immobility in the forced swimming test.Ginsenoside Rg1(48 mg/kg)significantly reduced the latency to eat in the novelty-suppressed feeding test,and ginsenoside Rg1(24 and 48 mg/kg)significantly increased the percentage of open arm entries and time in the elevated cross maze test.Serum corticosterone levels were significantly decreased in the ginsenoside Rg1 and Rb1 groups,serum IL-1β and IL-6 levels were significantly decreased in the ginsenoside Rg1(48 mg/kg)group,serum TNF-α and IL-6 levels were significantly decreased in the ginsenoside Rb1(33 mg/kg)group,and IL-1β,IL-6,and TNF-α levels in the hippocampus were significantly decreased in the ginsenoside Rg1(48 mg/kg)and Rb1(67 mg/kg)groups.Conclusions Both ginsenosides can regulate the hypothalamic-pituitary-adrenal axis and inhibit neuroinflammation,improving depression-and anxiety-like behaviors in rats induced by chronic unpredictable stress.Ginsenoside Rg1 has a significantly better anti-anxiety effect than Rb1.

Objective:This study aims to explore the synergistic effects of DIP and other medical insurance supply-side policies.Method:City A that has piloted DIP reform was set as the treatment group,and City B without reform was set as the control group.A total of 1 120 public medical institution samples from 2019 to 2022 were collected.The total medical expenses during hospitalization and some structural expenses were analyzed using DID method.Result:DIP had a significant inhibitory effect on the medical expenses,and the expenses of checkups and examinations during hospitalization in city A,but had no impact on the drug and the material expenses during hospitalization.Conclusion:DIP played a significant cost control role and effectively controlled the total medical expenses during hospitalization.The synergistic effects of price adjustment of medical services policy and national centralized drug/material procurement policy on cost control were insufficient.DIP synergized with other supply-side policies to promote rational medical cost structure.It is suggested that medical insurance departments should focus on the synergistic effects of medical insurance supply-side policies to jointly improve the efficiency of medical insurance fund utilization.

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.

Objective:To construct a prediction model for the clinical supply of blood components in Xi′an City from 2023 to 2025.Methods:Based on the blood supply data of the Blood Management Information System of Shaanxi Provincial Blood Center from January 2013 to December 2022, a gray prediction model and an exponential curve fitting model were used to construct the prediction model, and the optimal prediction model was determined according to the error parameters of the relevant indicators of the model. The supply of blood components in Xi′an from 2023 to 2025 was predicted.Results:The fitting equations of the exponential curve fitting model to predict the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were, x（1）（ t+1）=1.16e 0.04t， x（1）（ t+1）=1.04e 0.12t and x（1）（ t+1）=1.01e 1.10t, respectively. The mean absolute errors (mean relative errors) of the exponential curve fitting model in predicting the supply of suspended red blood cells, platelets and cryoprecipitate in Xi′an were 10 488.7 (0.05%), 2 114.9 (0.08%) and 3 089.6 (0.07%), respectively, which were lower than those of the gray prediction model, about 10 488.7 (3.44%), 2 152.78 (8.20%) and 3 441.35 (7.92%), respectively. The exponential curve fitting model predicted that the clinical supply of blood components in Xi′an would increase year by year from 2023 to 2025, and the clinical supply of suspended red blood cells, platelets, and cryoprecipitate in Xi′an would increase to 409 467 U, 69 818 therapeutic volume and 94 724 U, respectively by 2025. Conclusion:The exponential curve fitting model can make a good prediction of the clinical supply of blood components in Xi′an City.