ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

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

Objective:To investigate whether there is an association between the total dose of breast cancer radiotherapy, the mean dose of radiation field involving the heart and its substructures, and the long-term incidence of coronary heart disease (CHD) in patients.Methods:A retrospective analysis was conducted on 1125 patients with breast cancer who received radiotherapy with radiation fields involving the hear at Beijing Hospital from January 2009 to June 2022. The heart and its substructures of 54 patients were manually delineated, trained an automatic delineation model, and applied this model to the original radiotherapy planning images to automatically extract dosimetric parameters for the heart and substructures in the original plan. Based on the follow-up results, 1125 breast cancer patients were categorized into the CHD event group ( n=19) and non-event group ( n=1106). Wilcoxon rank-sum test, Chi-square test and adjustment for confounding factors using inverse probability weighting were used to compare the mean radiation dose received by the heart and its substructures, age at presentation, history of smoking, history of alcohol consumption, history of hypertension, and history of diabetes between two groups. The influencing factors of CHD were analyzed by univariate and multivariate logistic regression models. Results:The mean heart dose ( P=0.035), mean dose of right atrium ( P=0.049), right coronary artery ( P=0.013), septum ( P=0.045), and right ventricle ( P=0.039) of the event group were higher than that of the non-event group, and the differences were statistically significant. History of alcohol consumption was an independent risk factor for long-term CHD events in the breast cancer patients ( OR=7.35,95% CI: 1.56-25.58, P=0.004). After adjusting for confounding factors using inverse probability weighting, age at presentation was an independent risk factor for long-term CHD events ( OR=1.03, 95% CI: 1.01-1.05, P=0.004). Conclusions:In the breast cancer population with traditional high-risk factors of CHD receiving radiotherapy, the possibility of CHD probably remains high even if the dose of radiation field involving the heart and its substructures is low. Compared to traditional risk factors of CHD, the mean dose to the heart and its substructures in the radiation field of breast cancer patients exerts less impact on the occurrence of CHD after radiotherapy.

BACKGROUND:Pinoresinol diglucoside promotes bone formation and bone matrix synthesis and accelerates bone tissue repair.However,the mechanism of action and effects of this compound in osteoblasts need to be further explored. OBJECTIVE:To investigate the effect and mechanism of action of pinoresinol diglucoside on dexamethasone-treated osteoblasts based on the Wnt/β-catenin signaling pathway. METHODS:Different concentrations of dexamethasone groups and pinoresinol diglucoside groups were set to treat osteoblasts for 24 hours,and the optimal intervention concentrations were screened.Osteoblasts were treated with dexamethasone,pinoresinol diglucoside and inhibitor XAV-939.Then,control group,dexamethasone group,XVA-939 group,pinoresinol diglucoside group,pinoresinol diglucoside+XVA-939 group were set up.Cell counting kit-8 assay was used to detect cell activity.Alkaline phosphatase activity and caspase3/7 enzyme activity in cells were detected.Annexin V/PI staining and EdU assay were used to detect cell apoptosis and proliferation.Real-time qPCR and western blot were used to detect the mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen,respectively. RESULTS AND CONCLUSION:After dexamethasone and pinoresinol diglucoside intervened in osteoblasts for 24 hours,10 μmol/L dexamethasone was found to be the optimal intervention concentration for cell inhibition,and cell proliferation was most pronounced at a concentration of pinoresinol diglucoside of 100 μmol/L.Compared with the dexamethasone group,alkaline phosphatase activity was significantly enhanced(P<0.05)and caspase3/7 enzyme activity was significantly reduced(P<0.05)in the pinoresinol diglucoside group.Annexin V/PI staining and cell proliferation assay by EdU method showed that pinoresinol diglucoside inhibited apoptosis and promoted proliferation of osteoblasts after dexamethasone intervention.The mRNA and protein expression levels of Wnt3a,β-catenin,c-myc,osteocalcin,and type I collagen were significantly higher in the pinoresinol diglucoside group and pinoresinol diglucoside+XVA-939 group compared with the dexamethasone and XVA-939 groups(P<0.05).To conclude,pinoresinol diglucoside can inhibit osteoblast apoptosis after dexamethasone intervention,protect osteoblast activity and promote osteoblast proliferation by activating the Wnt/β-catenin signaling pathway,which may play a role in delaying steroid-induced osteonecrosis of the femoral head.

Objective To predict the poorly differentiated subtype of stage T1 invasive lung adenocarcinoma based on the morphological and quantitative characteristics of preoperative CT images.Methods The CT images,clinical information and pathological report of 333 cases with stage T1 lung adenocarcinoma in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and the Second Affiliated Hospital of Naval Medical University were retrospectively analyzed.All data were divided into histological subtypes according to the WHO Classification of Chest Tumors(5th Edition).CT signs include the maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,lobular sign,vacuole sign,air bronchial sign,halo sign,bronchial truncation sign,vascular cluster sign,pleural depression sign.Clinical factors included gender,age,smoking history,tumor markers,and spread through air spaces.Independent predictors of poorly differentiated subtypes of lung adenocarcinoma were obtained via univariate and multivariate logistic regression analysis,and the clinical model,CT model and combined model were constructed based on the analysis results.Results In univariate logistic regression analysis,gender,smoking history,tumor markers,spread through air spaces,maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,vacuole sign and vascular cluster sign were significantly related to poorly differentiated subtypes.Multivariate logistic regression analysis showed that gender,tumor markers,vacuole sign,minimum diameter,and nodule type were independent influencing factors of poorly differentiated subtypes of lung adenocarcinoma.Clinical model,CT model and combined model were constructed based on the analysis results.Area under the curve(AUC)of the clinical model,CT model and combined model were 0.772[95％confidence interval(CI)0.712-0.831],0.776(95％CI 0.714-0.837)and 0.825(95％CI 0.776-0.874)for the poorly differentiated subtypes,respectively.The combined model had a higher AUC,with the better prediction.There was significant difference in predicting lung adenocarcinoma poorly differentiated subtypes between the clinical model and combined model(P=0.019).Conclusion Logistic regression model based on CT signs has good diagnostic value in predicting poorly differentiated lung adenocarcinoma in stage Ⅰ.

Metastatic uveal melanoma (MUM) is a rare but highly invasive ocular malignant tumor with poor prognosis.At present, there is a lack of standardized methods for the treatment of MUM, resulting in poor prognosis.However, in recent years, the emergence of immune checkpoint inhibitors, new immune drug Tebenfos, comprehensive targeted therapy, combined sequential therapy and other treatment methods has brought new hope to MUM patients.This review aims to summarize the latest progress in the diagnosis, treatment, and prognosis of MUM.

In the context of the new medical reform,the formation mechanism of drug prices is one of the important is-sues of this round of medical reform.Drug prices involve the interests of drug companies,hospitals,patients,and other parties,so it is particularly important to establish a reasonable mechanism for the formation of drug prices to safeguard the interests of all parties.This paper first analyzes the characteristics of drugs and the drug market,and then discusses the actual situation and challenges faced by the formation mechanism of drug prices.On this basis,it proposes basic principles for drug pricing and opti-mization recommendations for the formation mechanism of drug prices in the context of the new medical reform.This can provide a reference for the country to formulate relevant drug price policies and promote the rational development of drug prices.

Metastatic uveal melanoma (MUM) is a rare but highly invasive ocular malignant tumor with poor prognosis.At present, there is a lack of standardized methods for the treatment of MUM, resulting in poor prognosis.However, in recent years, the emergence of immune checkpoint inhibitors, new immune drug Tebenfos, comprehensive targeted therapy, combined sequential therapy and other treatment methods has brought new hope to MUM patients.This review aims to summarize the latest progress in the diagnosis, treatment, and prognosis of MUM.

Objective To predict the poorly differentiated subtype of stage T1 invasive lung adenocarcinoma based on the morphological and quantitative characteristics of preoperative CT images.Methods The CT images,clinical information and pathological report of 333 cases with stage T1 lung adenocarcinoma in the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University and the Second Affiliated Hospital of Naval Medical University were retrospectively analyzed.All data were divided into histological subtypes according to the WHO Classification of Chest Tumors(5th Edition).CT signs include the maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,lobular sign,vacuole sign,air bronchial sign,halo sign,bronchial truncation sign,vascular cluster sign,pleural depression sign.Clinical factors included gender,age,smoking history,tumor markers,and spread through air spaces.Independent predictors of poorly differentiated subtypes of lung adenocarcinoma were obtained via univariate and multivariate logistic regression analysis,and the clinical model,CT model and combined model were constructed based on the analysis results.Results In univariate logistic regression analysis,gender,smoking history,tumor markers,spread through air spaces,maximum diameter,minimum diameter,location,nodule type,CT value,proportion of solid components,burr sign,vacuole sign and vascular cluster sign were significantly related to poorly differentiated subtypes.Multivariate logistic regression analysis showed that gender,tumor markers,vacuole sign,minimum diameter,and nodule type were independent influencing factors of poorly differentiated subtypes of lung adenocarcinoma.Clinical model,CT model and combined model were constructed based on the analysis results.Area under the curve(AUC)of the clinical model,CT model and combined model were 0.772[95％confidence interval(CI)0.712-0.831],0.776(95％CI 0.714-0.837)and 0.825(95％CI 0.776-0.874)for the poorly differentiated subtypes,respectively.The combined model had a higher AUC,with the better prediction.There was significant difference in predicting lung adenocarcinoma poorly differentiated subtypes between the clinical model and combined model(P=0.019).Conclusion Logistic regression model based on CT signs has good diagnostic value in predicting poorly differentiated lung adenocarcinoma in stage Ⅰ.

In the context of the new medical reform,the formation mechanism of drug prices is one of the important is-sues of this round of medical reform.Drug prices involve the interests of drug companies,hospitals,patients,and other parties,so it is particularly important to establish a reasonable mechanism for the formation of drug prices to safeguard the interests of all parties.This paper first analyzes the characteristics of drugs and the drug market,and then discusses the actual situation and challenges faced by the formation mechanism of drug prices.On this basis,it proposes basic principles for drug pricing and opti-mization recommendations for the formation mechanism of drug prices in the context of the new medical reform.This can provide a reference for the country to formulate relevant drug price policies and promote the rational development of drug prices.