Objective To construct a prediction model for the population with hypertension and diabetes to assess the risk of chronic kidney disease (CKD), and to provide a scientific basis for formulating targeted CKD prevention and control measures. Methods Based on physical examination data from community residents aged 60 years and above in Nanjing in 2022, 10 221 patients with hypertension and diabetes were selected as the study subjects. Variables associated with CKD prevalence were screened using univariate analysis, and further variable selection was performed using LASSO regression. Finally, a CKD risk prediction model was constructed based on logistic regression. The model's performance was evaluated using the ROC curve and calibration curve. Results The prevalence rate of CKD in the study population was 22.71%, with a mean age of 71.66 years. LASSO regression identified seven variables associated with CKD: age, blood urea nitrogen (BUN), hemoglobin, uric acid, triglyceride-glucose (TyG) index, urine protein-to-creatinine ratio (UPCR), and medical insurance type. The final logistic regression model incorporated six variables: age [OR=1.067 (95% CI: 1.058-1.076)], BUN [OR=1.377 (95% CI: 1.338-1.418)], hemoglobin [OR=0.992 (95% CI: 0.989-0.995)], uric acid [OR=1.004 (95% CI: 1.003-1.004)], TyG index [OR=1.445 (95% CI: 1.324-1.577)], and self-payment medical insurance [OR=1.732 (95% CI: 1.542-1.945)]. The model had an AUC of 0.759 (95% CI: 0.747-0.770) and a Brier score of 0.140 (95% CI: 0.136-0.145), indicating good predictive performance. The calibration curve showed good agreement between the predicted risk and the observed value. Conclusion The constructed LASSO-logistic regression risk prediction model in this study can effectively assess the risk of CKD in elderly individuals aged 60 years and above with hypertension and diabetes, providing a basis for early identification of high-risk individuals and the formulation of targeted CKD prevention and control measures.

OBJECTIVE To confirm trigger items for adverse drug reaction （ADR） induced by bevacizumab， to identify and analyze the occurrence of related ADR， and to establish a predictive model for severe adverse reaction （SAR） caused by this drug. METHODS Based on the global trigger tool （GTT） theory， and referencing the GTT White Paper， drug package inserts and relevant literature， trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items， electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects （divided into training and test sets at a ratio of 7∶3）， candidate feature variables were selected from 39 related variables using the Boruta algorithm， and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features， Logistic Regression， Extreme Gradient Boosting， Light Gradient Boosting Machine， Random Forest， and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve （AUC） of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations （SHAP） method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined， comprising 17 laboratory indicators， 13 clinical manifestations， and 8 intervention measures. In total， 483 patients with positive trigger items were included， and 318 patients with bevacizumab-induced ADR were identified， including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% （708/1 625） and 63.84% （318/483）， respectively. Bevacizumab-induced ADR involved 7 systems/organs， with the hematological system being the most frequently involved （64.15%）. The Boruta algorithm selected 7 vari ables： serum potassium， hematocrit， albumin-to-globulin ratio， prealbumin， hypertension history， age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR （OR＝0.234， P ＝0.002）， while a history of hypertension （OR＝2.642， P ＝0.006） and increased age （OR＝1.040， P ＝0.025） were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC， F1 score and recall rate （0.761， 0.447， 0.607）， compared to other models. SHAP evaluation results indicated that variables such as serum potassium， hematocrit， and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR， whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

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 the correlation between the inflammatory burden index(IBI)and major adverse cardiovascular events(MACEs)in patients with ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI),and to assess the efficacy of IBI in predicting in-hospital and long-term MACEs.Methods This retrospective study included 465 STEMI patients who received PCI treatment in No.904 Hospital of Joint Logistics Support Force of PLA from Dec.2017 to Dec.2021.The IBI was calculated for each patient.The predictive value for in-hospital and long-term MACEs was evaluated using receiver operating characteristic(ROC)curves,and the area under curve(AUC)was calculated.The population was grouped based on the optimal IBI cut-off value for clinical characteristic analysis.Multivariate logistic regression and Cox regression analyses were used to identify factors independently associated with MACEs.The Kaplan-Meier estimator and log-rank test were used to assess the MACE risk of different IBI groups.Results The AUC value for predicting MACEs during hospitalization in STEMI patients using IBI was 0.687,and the AUC value for predicting long-term MACEs was 0.634.Multivariate logistic regression analysis revealed that a high IBI 102.33 mg/L)independently increased the risk of MACEs during hospitalization in STEMI patients(odds ratio=10.900,95％confidence interval[95％CI]4.273-29.180,P＜0.001).Multivariate Cox regression analysis further indicated that during long-term follow-up of STEMI patients,a high IBI(≥55.88 mg/L)independently predicted MACEs(hazard ratio=1.989,95％CI 1.128-3.506,P=0.018).Conclusion IBI is a valuable predictor for the occurrence of MACEs during hospitalization and long-term follow-up after PCI in STEMI patients.

Objective To investigate the correlation between c-MYC expression and mitochondrial metabolism in malignant duct epithelial cells of pancreatic cancer patients.Methods GEPIA database was used to analyze the correlation between c-MYC expression and overall survival.The expression of c-MYC in tumor tissues was detected by immunohistochemical staining.The difference of DLAT and DLST gene expression between tumor and normal tis-sues was compared in GEPIA database.HP A database was used to analyze the correlation between c-MYC and DLAT,DLST expression in tumor tissues.The expression level of DLAT and DLST in tumor tissues was evaluated by immunofluorescence staining.Results The high expression of c-MYC gene was negatively correlated with overall survival(P＜0.01).The level of c-MYC protein was positively correlated with the pathological grade of PanIN.Compared with normal tissues,the expression of DLAT and DLST genes in pancreatic cancer cells was increased(P＜0.01).The protein level of c-MYC was positively correlated with those of DLAT and DLST(P＜0.01,P＜0.001).Conclusions The high expression of mitochondrial metabolic enzymes DLAT and DLST in pancreatic ductal adenocarcinoma cells is significantly correlated with the expression level of c-MYC,which increases with the progression of pancreatic cancer.

OBJECTIVE To prepare a self-microemulsifying drug delivery system(SMEDDS) for the oral administration of nebivolol hydrochloride(NBH) and to conduct in vitro evaluation. METHODS The solubility of NBH was determined using various oil phases, surfactants, and co-surfactants. The composition of the blank self-microemulsifying formulation was determined using pseudo-ternary phase diagrams. A centralcomposite design-response surface method was employed to screen and optimize the formulation variables, and an excess amount of NBH raw material was incorporated to determine the drug loading capacity. RESULTS The optimized composition of the NBH-SMEDDS formulation consisted of medium-chain glycerides, capryl caproyl macrogol glycerides, and 2-(2-ethoxyethoxy) ethyl acetate at a ratio of 20∶48∶32, with a drug loading capacity of 20.05 mg. The particle size, self-emulsification time, and particle size distribution range of the formulation were in agreement with the predicted values. Dissolution testing demonstrated that the overall dissolution trend of NBH-SMEDDS in the medium was higher than that of NBH powder and NBH ordinary tablet. The stability of NBH-SMEDDS was found to be satisfactory under accelerated conditions for 1, 2, and 3 months. CONCLUSION The SMEDDS shows potential for enhancing the in vitro dissolution of NBH and demonstrates good stability.

OBJECTIVE To solve the problem of insolubility of itraconazole, improve its dissolution in vitro, and provide a reference for further industrial scale-up of the itraconazole multiparticle system. METHODS Itraconazole multiparticle system pellets were dissolved in an organic solvent and prepared in a fluidized bed by bottom spraying. Itraconazole and hydroxypropyl methylcellulose were sprayed onto the surface of the sucrose pellet core to form a uniform solid dispersion. The preparation parameters of the fluidized bed bottom spray coating were investigated by single factor method. The mass ratio of drug to carrier and core weight gain of the itraconazole multiparticle system were optimized by central composite design and response surface methodology with accumulative dissolution rate, application efficiency and adhesion rate as response values. Samples were prepared to verify the optimized prescription, the microscopic hierarchical structure of the itraconazole multiparticle system was observed by scanning electron microscope, and the solid dispersion in the itraconazole multiparticle system pellets was characterized by differential scanning calorimetry(DSC) and X-ray diffraction(XRD). The dissolution curves of itraconazole pellets and the physical mixture in 0.1 mol·L−1 HCl dissolution medium were compared to verify the solubilization effect. RESULTS Single factor method was used to determine the bottom spray coating parameters of the fluidized bed. The pumping speed was set as 3.0−5.0 mL·min−1, the atomization pressure was set as 1.5 bar, the inlet air volume was set as 110 m3·h−1, and the material temperature was set as 35 ℃. According to the central composite design and response surface methodology, the mass ratio of drug to carrier of the optimized prescription was 1∶1.5 and the core weight of the pill was 75%, and the response values reached the expected value. The result of scanning electron microscopy showed that the diameter of the itraconazole multiparticle system pellet was about 910 µm, the diameter of the sucrose pellet core was about 570 µm, the thickness of the drug loading layer was about 110 µm, and the thickness of encapsulation layer was about 11 µm. The results of DSC and XRD showed that itraconazole formed a uniform solid dispersion in the itraconazole multiparticle system pellets, which was amorphous. In the dissolution medium of 0.1 mol·L−1 HCl, the accumulative dissolution rate of the multiparticle system after 90 min was about 10 times that of the physical mixture, which showed that the solubilization effect was remarkable. CONCLUSION The dissolution of itraconazole in vitro can be significantly improved by processing itraconazole into pellets with multiparticle system and forming solid dispersion.

Objective To study the effect of carboxyamidotriazole-orotate(CTO)on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells.Methods Human pancreatic cancer cell lines AsPC-1,AsPC-1/GEM(AR),PANC-1 and MiaPaCa-2 were used as the study subjects;cell survival rate was detected by sulfo-nylrhodamine B(SRB);the mRNA level of key genes for fatty acid synthesis was detected by qPCR;the protein level of the AMPK/ACC pathway was detected by Western blot;intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS).Results Comparing to control group,CTO significantly de-creased the cell viability of AsPC-1,AR,PANC-1,and MiaPaCa-2(P＜0.05).CTO down-regulated the mRNA level of key fatty acid synthesis genes(P＜0.05).CTO significantly reduced the protein expression of AMPK,ACC and c-Myc(P＜0.05),while increasing the protein expression of p-AMPK and p-ACC(P＜0.05).CTO decreased lipid metabolite content in AR cells(P＜0.05).Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway,down-regulates the expression of fatty acid synthesis-related genes,and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1,AR,PANC-1 and MiaPaCa-2.