OBJECTIVE To investigate the effect of Huangqin decoction （HQD）-based self-assembled nanoparticles （SAN） co-loaded with terbinafine （TBF） （TBF-HQD-SAN NPs） on the transdermal absorption of TBF. METHODS High-speed centrifugation combined with dialysis was used to separate HQD-SAN， and TBF-HQD-SAN NPs were obtained by loading TBF using the ultrasound magnetic stirring method； the particle size distribution， Zeta potential and polydispersity index （PDI） of the nanoparticle were characterized， and the encapsulation efficiency （EE） and drug loading （DL） of TBF were determined； using in vitro and in vivo transdermal experiments， the differences in transdermal performance between TBF-HQD-SAN NPs and TBF raw materials， as well as TBF and HQD-SAN physical mixture （TBF-HQD-SAN PM）， were compared and analyzed. RESULTS TBF- HQD-SAN NPs were spherical with a particle size of （177.60±2.57） nm， a PDI of 0.197 4±0.007 9， and a Zeta potential of （－14.63±0.85） mV. The EE and DL of TBF were （99.49±0.71）% and （3.22±0.10）% ， respectively. In vitro transdermal experiments， compared with TBF raw materials， the steady-state permeation rate （Jss） and skin retention of TBF-HQD-SAN NPs increased by 3.34 times and 27.56 times， respectively （P＜0.05）； compared with TBF-HQD-SAN PM， its Jss and skinretention were increased by 2.04 times and 7.44 times， respectively （P＜0.05）. In vivo transdermal experiments 69号） showed that， the area under the drug-time curve and the maximum concentration of TBF-HQD-SAN NPs increased by 2.13 times and 2.06 times respectively compared to TBF raw materials， and increased by 1.59 times and 1.65 times respectively compared to TBF-HQD-SAN PM （P＜0.05）. CONCLUSIONS TBF-HQD-SAN NPs can significantly enhance the in vitro and in vivo transdermal absorption efficiency and skin retention of TBF.

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Objective Utilizing patient journey mapping to decipher disease management behaviors,barriers,and needs in young and middle-aged liver transplant recipients,providing implications for self-management optimization and quality of life improvement.Methods Using purposive sampling,12 young and middle-aged liver transplant patients who attended outpatient clinics or were hospitalized in liver transplant center of a tertiary hospital in Qingdao were selected for semi-structured interviews from September to November 2024.Thematic extraction and analysis were performed using Colaizzi's 7-step analysis,ultimately resulting in the development of a patient journey map.Results The journey stages were divided into transplantation decision-making period,transplantation waiting period,perioperative period,and post-discharge management period,and the journey key elements were designed as behaviors,barriers,and needs.A total of 25 themes were extracted,including behaviors(such as referrals to higher-level hospitals,verification of treatment options),barriers(such as lack of decision-making autonomy,health information-seeking barriers),and needs(such as shared decision-making,financial assistance).Ultimately,resulting in a map of the disease management journey for young and middle-aged liver transplant recipients.Conclusion The behaviors,barriers,and needs in disease management among young and middle-aged liver transplant recipients demonstrate distinct phase-specific patterns.Healthcare providers should deliver precise and dynamic interventions tailored to each clinical phase,aiming to foster optimal self-management behaviors,address phase-specific banriers,and meet evolving patient needs throughout the transplant continuum.

Objective:To explore the relationship between blood urea nitrogen (BUN) levels and the risk of all-in-hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pneumonia.Methods:This study was a secondary analysis of a multicenter, retrospective cohort study, with data sourced from the DATADRYAD database of five hospitals in Japan (Kameda Hospital, Hyogo Hospital, Awa Hospital, Saiseikai Hospital, and Ichinomiyanishi Hospital). The database included 1 237 cases of AECOPD with pneumonia hospitalized from April 2008 to August 2019, aged≥40 years. After excluding 11 cases with missing BUN level data at admission, a total of 1 226 patients were included in this secondary analysis. BUN level at admission was used as the target independent variable, and all-cause in-hospital mortality during hospitalization was the dependent variable. Risk ratio regression analysis was used to assess the independent correlation between BUN level and the risk of in-hospital mortality due to AECOPD complicated with pneumonia; generalized additive models and smoothing curve fitting methods were applied to explore nonlinear relationships, followed by subgroup analyses to evaluate the consistency of the association across different subgroups and further validate the reliability of the findings.Results:After adjusting for potential confounding factors such as gender and age, BUN levels were positively correlated with the risk of all-cause in-hospital mortality [ OR=1.09(95% CI: 1.01-1.17), P=0.032]. There was a relationship between BUN levels and the risk of all-cause in-hospital mortality, with a turning point at 43.3 mg/dl. The sizes and 95% CI on either side of the turning point were 1.04(0.93-1.16) and 1.08(1.05-1.12), respectively. When BUN>43.3 mg/dl, BUN was correlated with the risk of all-cause in-hospital mortality, with an 8.0% increase in the risk of death for every 1.0 mg/dl increase in BUN ( P<0.05); when BUN<43.3 mg/dl, there was no significant relationship between BUN and the risk of all-cause in-hospital mortality ( P=0.534). Subgroup analysis indicated that in each subgroup of gender, age, source hospital, fever, respiratory, heart rate, crackles in the lungs, change in mental status, corticosteroid therapy, intubation, complete assistance with activities of daily living, medical insurance, and length of hospital stay, the OR value of BUN level had good stability (all OR>1.00) with the risk of all-cause mortality in AECOPD patients with pneumonia. Conclusions:BUN levels are associated with the risk of all-cause in-hospital mortality in patients with AECOPD complicated with pneumonia. When BUN>43.3 mg/dl, BUN levels are positively correlated with the risk of all-cause in-hospital mortality in these patients.

AIM: To investigate the association between HOXA1 and FOXF2 gene variants and genetic susceptibility in multigenerational families with exotropia, and to elucidate the molecular genetic etiological mechanisms of exotropia.METHODS:A total of 10 multigenerational families with a definitive history of exotropia were recruited from September 2023 to February 2025, comprising 165 members(87 exotropia patients and 78 normal controls). Detailed ophthalmological examinations were performed, family pedigrees were constructed, peripheral blood samples were collected, genomic DNA was extracted, and PCR amplification followed by Sanger sequencing were used to detect exons and flanking sequences of the HOXA1 and FOXF2 genes. Identified variants were subjected to pathogenicity classification and association analyses.RESULTS:Among the 10 families, 5 variant sites in HOXA1(c.218G>A, c.385C>T, c.496A>G, c.652T>C, c.874C>T)and 4 in FOXF2(c.102C>T, c.344G>A, c.576T>C, c.892A>G)were identified. The HOXA1 c.496A>G variant showed statistically significant differences between carrier and noncarrier in exotropia angle, exotropia type, stereoscopic vision, and parallax(all P<0.05). The age of onset of FOXF2 gene c.344G>A mutation carrier group was younger than that of the non-carrier group(t=3.55, P=0.004).CONCLUSION:HOXA1 and FOXF2 gene variants are significantly associated with genetic susceptibility to exotropia, particularly influencing age of onset and deviation angle, offering novel targets for molecular diagnosis and precision treatment of exotropia.

Objective To investigate the relationship between serum C-C motif ligand 23 (CCL23),Stanniocalcin-1 (STC1) levels and prognosis in patients with severe hypertensive intracerebral hemorrhage (HICH). Methods A total of 122 severe HICH patients who visited the Department of Neurosurgery,Hohhot First Hospital from March 2021 to March 2023 were regarded as the study subjects (HICH group),122 patients with mild HICH during the same period (mild group) and 122 healthy individuals who underwent physical examinations were considered healthy. HICH patients were separated into survival group(n=94) and death group(n=28)based on prognosis. ELISA was applied to detect serum levels of CCL23 and STC1. Spearson on method was used to analyze correlations and multivariate COX regression was used to investigate the influencing factors of prognosis in HICH patients,and ROC curve was applied to analyze the predictive value of serum CCL23 and STC1 levels for the prognosis. Kaplan-Meier was applied to analyze the relationship between serum CCL23,STC1 levels and clinical outcomes. Results Serum CCL23(53.32±10.85pg/ml,78.49±11.21pg/ml,112.47±11.53pg/ml)and STC1 (15.12±2.63ng/ml,19.07±2.58ng/ml,22.15±2.75ng/ml)levels in the healthy group,mild disease group and HICH group were increased successively,and the differences was statistically significant (F=856.967,215.043,all P<0.05). The serum levels of CCL23 (108.02±13.51pg/ml) and STC1 (21.06±3.28ng/ml) in the survival group were lower than those in the death group(127.41±13.55 pg/ml,25.83±3.23 ng/ml),the Glasgow coma (GCS) score (8.95±0.92 ) of the survival group was higher than that of the death group(7.61±0.77),and the differences were statistically significant (t=6.663,6.810,7.005,all P<0.001). The serum levels of CCL23 and STC1 were negatively correlated with GCS score (r=-0.481,-0.426,all P<0.001). CCL23[OR(95％CI):1.240(1.091～1.409)],STC[OR(95％CI):1.754(1.215～2.533)]and GCS[OR(95％CI):0.087(0.020～0.382)]score were the influencing factors for poor prognosis in HICH patients . The AUC(95％CI) of CCL23 combined STC1 in the prediction of the prognosis of HICH patients was 0.939 (0.880～0.974) which was higher than that of single diagnosis (Z=1.974,2.040,P=0.048,0.041),the sensitivity and specificity of combined diagnosis were 85.71％ and 94.68％,respectively. The 6-month follow-up survival rate of patients with high expression of CCL23 and STC1 (51.06％ vs 93.33％,56.86％ vs 91.55％) was lower than that of patients with low expression of CCL23 and STC1,and the differences were statistically signrficant (Log rank x2=34.777,23.781,all P<0.05). Conclusion The serum levels of CCL23 and STC1 are high in severe HICH patients,which are closely related to their prognosis. High expression of CCL23 and STC1 may indicate poor clinical outcomes in patients.

Objective To investigate the relationship between serum C-C motif ligand 23 (CCL23),Stanniocalcin-1 (STC1) levels and prognosis in patients with severe hypertensive intracerebral hemorrhage (HICH). Methods A total of 122 severe HICH patients who visited the Department of Neurosurgery,Hohhot First Hospital from March 2021 to March 2023 were regarded as the study subjects (HICH group),122 patients with mild HICH during the same period (mild group) and 122 healthy individuals who underwent physical examinations were considered healthy. HICH patients were separated into survival group(n=94) and death group(n=28)based on prognosis. ELISA was applied to detect serum levels of CCL23 and STC1. Spearson on method was used to analyze correlations and multivariate COX regression was used to investigate the influencing factors of prognosis in HICH patients,and ROC curve was applied to analyze the predictive value of serum CCL23 and STC1 levels for the prognosis. Kaplan-Meier was applied to analyze the relationship between serum CCL23,STC1 levels and clinical outcomes. Results Serum CCL23(53.32±10.85pg/ml,78.49±11.21pg/ml,112.47±11.53pg/ml)and STC1 (15.12±2.63ng/ml,19.07±2.58ng/ml,22.15±2.75ng/ml)levels in the healthy group,mild disease group and HICH group were increased successively,and the differences was statistically significant (F=856.967,215.043,all P<0.05). The serum levels of CCL23 (108.02±13.51pg/ml) and STC1 (21.06±3.28ng/ml) in the survival group were lower than those in the death group(127.41±13.55 pg/ml,25.83±3.23 ng/ml),the Glasgow coma (GCS) score (8.95±0.92 ) of the survival group was higher than that of the death group(7.61±0.77),and the differences were statistically significant (t=6.663,6.810,7.005,all P<0.001). The serum levels of CCL23 and STC1 were negatively correlated with GCS score (r=-0.481,-0.426,all P<0.001). CCL23[OR(95％CI):1.240(1.091～1.409)],STC[OR(95％CI):1.754(1.215～2.533)]and GCS[OR(95％CI):0.087(0.020～0.382)]score were the influencing factors for poor prognosis in HICH patients . The AUC(95％CI) of CCL23 combined STC1 in the prediction of the prognosis of HICH patients was 0.939 (0.880～0.974) which was higher than that of single diagnosis (Z=1.974,2.040,P=0.048,0.041),the sensitivity and specificity of combined diagnosis were 85.71％ and 94.68％,respectively. The 6-month follow-up survival rate of patients with high expression of CCL23 and STC1 (51.06％ vs 93.33％,56.86％ vs 91.55％) was lower than that of patients with low expression of CCL23 and STC1,and the differences were statistically signrficant (Log rank x2=34.777,23.781,all P<0.05). Conclusion The serum levels of CCL23 and STC1 are high in severe HICH patients,which are closely related to their prognosis. High expression of CCL23 and STC1 may indicate poor clinical outcomes in patients.

Objective:To explore the relationship between blood urea nitrogen (BUN) levels and the risk of all-in-hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pneumonia.Methods:This study was a secondary analysis of a multicenter, retrospective cohort study, with data sourced from the DATADRYAD database of five hospitals in Japan (Kameda Hospital, Hyogo Hospital, Awa Hospital, Saiseikai Hospital, and Ichinomiyanishi Hospital). The database included 1 237 cases of AECOPD with pneumonia hospitalized from April 2008 to August 2019, aged≥40 years. After excluding 11 cases with missing BUN level data at admission, a total of 1 226 patients were included in this secondary analysis. BUN level at admission was used as the target independent variable, and all-cause in-hospital mortality during hospitalization was the dependent variable. Risk ratio regression analysis was used to assess the independent correlation between BUN level and the risk of in-hospital mortality due to AECOPD complicated with pneumonia; generalized additive models and smoothing curve fitting methods were applied to explore nonlinear relationships, followed by subgroup analyses to evaluate the consistency of the association across different subgroups and further validate the reliability of the findings.Results:After adjusting for potential confounding factors such as gender and age, BUN levels were positively correlated with the risk of all-cause in-hospital mortality [ OR=1.09(95% CI: 1.01-1.17), P=0.032]. There was a relationship between BUN levels and the risk of all-cause in-hospital mortality, with a turning point at 43.3 mg/dl. The sizes and 95% CI on either side of the turning point were 1.04(0.93-1.16) and 1.08(1.05-1.12), respectively. When BUN>43.3 mg/dl, BUN was correlated with the risk of all-cause in-hospital mortality, with an 8.0% increase in the risk of death for every 1.0 mg/dl increase in BUN ( P<0.05); when BUN<43.3 mg/dl, there was no significant relationship between BUN and the risk of all-cause in-hospital mortality ( P=0.534). Subgroup analysis indicated that in each subgroup of gender, age, source hospital, fever, respiratory, heart rate, crackles in the lungs, change in mental status, corticosteroid therapy, intubation, complete assistance with activities of daily living, medical insurance, and length of hospital stay, the OR value of BUN level had good stability (all OR>1.00) with the risk of all-cause mortality in AECOPD patients with pneumonia. Conclusions:BUN levels are associated with the risk of all-cause in-hospital mortality in patients with AECOPD complicated with pneumonia. When BUN>43.3 mg/dl, BUN levels are positively correlated with the risk of all-cause in-hospital mortality in these patients.

Objective Utilizing patient journey mapping to decipher disease management behaviors,barriers,and needs in young and middle-aged liver transplant recipients,providing implications for self-management optimization and quality of life improvement.Methods Using purposive sampling,12 young and middle-aged liver transplant patients who attended outpatient clinics or were hospitalized in liver transplant center of a tertiary hospital in Qingdao were selected for semi-structured interviews from September to November 2024.Thematic extraction and analysis were performed using Colaizzi's 7-step analysis,ultimately resulting in the development of a patient journey map.Results The journey stages were divided into transplantation decision-making period,transplantation waiting period,perioperative period,and post-discharge management period,and the journey key elements were designed as behaviors,barriers,and needs.A total of 25 themes were extracted,including behaviors(such as referrals to higher-level hospitals,verification of treatment options),barriers(such as lack of decision-making autonomy,health information-seeking barriers),and needs(such as shared decision-making,financial assistance).Ultimately,resulting in a map of the disease management journey for young and middle-aged liver transplant recipients.Conclusion The behaviors,barriers,and needs in disease management among young and middle-aged liver transplant recipients demonstrate distinct phase-specific patterns.Healthcare providers should deliver precise and dynamic interventions tailored to each clinical phase,aiming to foster optimal self-management behaviors,address phase-specific banriers,and meet evolving patient needs throughout the transplant continuum.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.