Objective To investigate the pharmacokinetics of flumazenil sublingual spray in Beagle dogs. Methods Twelve Beagle dogs were grouped in a two-period, two-sequence crossover study design, receiving intravenous injection or sublingual spray administration. Blood samples （2 ml） were collected from the leg vein at 0.16, 0.33, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 6.0 and 8.0 h post-dosing. The plasma concentration of flumazenil was quantified by liquid chromatography-tandem mass spectrometry （LC-MS/MS） with an internal standard method, and key pharmacokinetic parameters were calculated. Results The t_max values for flumazenil injection and sublingual spray were 0.17 h and （0.28±0.10） h, respectively; c_max values were （8.14±0.81） and （10.41±1.72） ng/ml; and AUC_0–∞ values were （6.90±0.99） and （10.97±1.68）（ng·h）/ml. The bioavailability of the sublingual spray was （80.79±0.14）%. Conclusion Flumazenil sublingual spray demonstrated rapid absorption and high bioavailability in Beagle dogs.

The construction of a new cultural system for high-quality development in public hospitals serves as a crucial pillar for achieving their high-quality advancement.During this developmental processe stablishing a cultural framework that aligns with the new development model holds particular significance.Through content analysis methodology,it identifies 18 core elements of the new cultural system for high-quality development in public hospitals.Furthermore it synthesizes seven implementation pathways across three dimensions-organizational patientand employee perspectives:digital leadership organizational reform capability talent innovation capability resource integration capability normative constraint force value co-creation capability and employee support capability.These findings provide both theoretical and practical references for cultivating new cultural constructs that facilitate high-quality development in public hospitals.

Objective:To analyze the evaluation of the “1+1+2M” healthcare management model (outpatient core medical staff+ward core medical staff+multi interdisciplinary team+multi department coordination) by healthcare workers in a large public hospital and its influencing factors.Methods:It was a cross-sectional study, using the judgment sampling method to select 70 healthcare workers in the hospital healthcare department in November 2024. A self-designed public hospital healthcare management model evaluation questionnaire was used to investigate the “1+1+2M” healthcare management model. A total of 70 questionnaires were distributed, and 70 valid questionnaires were collected (100%). The basic information, team integration, human resource allocation, and evaluation of healthcare management models in the healthcare workers were collected. The factors affecting healthcare worker evaluation were identified with Kruskal Wallis test and multiple logistic regression analysis.Results:Among the 70 healthcare workers included in the analysis, there were 30 doctors, 30 nursing staff, and 10 management/technical personnel; 19 males and 51 females; more than 70% of the participants were aged 50 years or younger; the length of service was (19.11±9.44) years, and the length of service for healthcare was (9.79±6.06) years. Healthcare workers showed high satisfaction with the “1+1+2M” healthcare management model, with an overall satisfaction rate of 87.14% (61/70). The evaluation of work collaboration, business norms, and mode configuration by healthcare workers was positively correlated with the evaluation of healthcare management mode [very satisfied with health management mode: relatively satisfied with work collaboration ( OR=0.064, 95% CI: 0.004-0.965), satisfied with business norms ( OR=0.018, 95% CI: 0.001-0.312), relatively satisfied with business norms ( OR=0.061, 95% CI: 0.004-0.938), satisfied with mode configuration ( OR=0.006, 95% CI: 0.000-0.111); satisfied with health management mode: satisfied with business norms ( OR=0.049, 95% CI: 0.005-0.498), satisfied with mode configuration ( OR=0.074, 95% CI: 0.006-0.943)] (all P<0.05). Conclusions:The health care staff in a large public hospital have a good evaluation of the operation effect of the “1+1+2M”health management model. The higher the evaluation of work collaboration, business norms, and model configuration by the health care staff, the higher the overall satisfaction with the health management model.

Objective:This study aimed to propose an innovative modular surgical technique and explore its safety and application value in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy for advanced proximal gastric cancer invading the greater curvature.Methods:A retrospective collection was conducted on 34 patients with proximal gastric cancer invading the greater curvature who underwent laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy in the same center from October 2020 to December 2022. The technical key points, precautions and crucial steps of the modular surgical technique were summarized, and the Clinical indicators were analyzed.Results:All 34 patients successfully completed the operation under laparoscopy without conversion to open surgery. The average operation duration was 151.9±4.1 minutes, and the duration of splenic hilar lymphadenectomy was 12.9±1.5 minutes. The median intraoperative blood loss was 50(20, 50) ml, and the blood loss during splenic hilar lymphadenectomy was 5 (2, 5) ml. The median number of harvested lymph nodes was 32.0 (23.5,39.5), and the number of submitted No.10 lymph nodes was 3 (2, 4). The metastasis rate of No.10 lymph nodes was 20.6% (7/34). No patient had intraoperative complications. During the postoperative hospital stay, one patient had incision infection (Clavien-Dindo I), and one patient had pulmonary infection (Clavien-Dindo II). The time for the first postoperative feeding was 3 (2, 5) days, the time for the first postoperative flatus was 2 (2,3) days, the time for the first postoperative defecation was 3 (3, 4) days, the total postoperative drainage volume was 1047.5 (607.5,1397.5) mL, the time for postoperative drainage tube removal was 7 (6, 9) days, and the length of postoperative hospital stay was 7.0 (6.0, 9.5) days.Conclusions:The application of the innovative modular surgical technique in laparoscopic total gastrectomy combined with spleen-preserving hilar lymphadenectomy can simplify surgical process and enable safe, precise and comprehensive dissection of splenic hilar lymph nodes.

Current experimental and computational methods have limitations in accurately and efficiently classi-fying ion channels within vast protein spaces.Here we have developed a deep learning algorithm,GPT2 Ion Channel Classifier(GPT2-ICC),which effectively distinguishing ion channels from a test set con-taining approximately 239 times more non-ion-channel proteins.GPT2-ICC integrates representation learning with a large language model(LLM)-based classifier,enabling highly accurate identification of potential ion channels.Several potential ion channels were predicated from the unannotated human proteome,further demonstrating GPT2-ICC's generalization ability.This study marks a significant advancement in artificial-intelligence-driven ion channel research,highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data.Moreover,it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

Objective To analyze the characteristics of weekend surgery,and explore to shorten the preoperative hospital stay and average hospital stay of patients.Method Extract actual data on the number of discharged surgical patients and length of hospital stay,and use the Questionnaire Star to investigate the recognition of weekend surgeries by medical staff.Using chi square test and independent sample rank sum test,compare the differences in patients and surgical characteristics between weekend surgery and non weekend surgery,and analyze the influencing factors of surgical physicians using binary logistic regression model.Result The median length of hospital stay(3.0 days)and preoperative hospital stay(0.5 days)was lower than that of non weekend surgery patients(5.0,1.5 days);The proportion of fourth grade surgeries on weekends(28.9％)was lower than that of non weekend surgeries(37.0％);The consultation rate(10.74％)was lower than that of non weekend surgeries(17.0％);The proportion of daytime pilot surgeries(30.7％)was higher than that of non weekend surgeries(20.4％).The factors with the highest recognition among medical staff for conducting weekend surgeries were:improving patient satisfaction(84.7％)and reducing preoperative waiting risks(84.4％).The lowest factors were family support(45.5％)and multi departmental assistance and cooperation(58.8％).Conclusion Weekend surgery effectively shortens the average preoperative and average hospitalization days.Move the hospitalization consultation required for comorbidities management and preoperative examinations to the outpatient department.Mobilize the coordination and supporting resources of various departments within the hospital,and organically integrate various surgical methods such as weekend surgery and day surgery to improve the efficiency of medical operation.

Objective:To discuss the effect of KIAA1522 on the proliferation,migration,and invasion of lung cancer cells,and to clarify its signaling mechanism.Methods:Bioinformatics analysis was used to detect the expression levels of KIAA1522 mRNA and protein in 75 cases of human non-small cell lung cancer(NSCLC)tissues and adjacent normal lung tissues;immunohistochemical staining was used to detect the expression of KIAA1522 protein in NSCLC tissue and adjacent normal lung tissues;Western blotting method was used to detect the expression level of KIAA1522 protein in various lung cancer cell lines.KIAA1522-small interfering(siRNA)and over-expression plasmids were transfected into the lung cancer H1299 and A549 cells,respectively.The KIAA1522-siRNA experiment was divided into blank group,negative control group(si-NC group),KIAA1522-siRNA#1 group,and KIAA1522-siRNA#2 group.The KIAA1522 over-expression experiment was divided into control group,empty vector control group(OE-NC group,transfected with KIAA1522 over-expression empty vector plasmid),KIAA1522 overexpression group(OE-KIAA1522 group,transfected with KIAA1522 over-expression plasmid),KIAA1522 over-expression+MK2206 group[OE-KIAA1522+MK2206 group,co-transfected with KIAA1522 over-expression plasmid and protein kinase B(AKT)signaling pathway inhibitor MK2206],and MK2206 group(transfected with MK2206).Western blotting method was used to verify the transfection efficiencies of the cells in various groups;MTT assay was used to detect the proliferation activities of the lung cancer cells in various groups;cell scratch assay was used to detect the migration rates of lung cancer cells in various groups;Transwell chamber assay was used to detect the numbers of invasion lung cancer cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated AKT(p-AKT),total AKT(t-AKT),cyclin D1(Cyclin D1),vascular endothelial growth factor(VEGF),and epithelial-mesenchymal transition(EMT)-related proteins[vimentin(Vimentin),N-cadherin(N-cadherin),and E-cadherin(E-cadherin)]proteins in the cells in various groups.Results:The bioinformatics analysis results showed that compared with adjacent normal lung tissue,the expression levels of KIAA1522 mRNA and protein in NSCLC tissue were significantly increased(P<0.05 or P<0.01).The immunohistochemistry staining results showed that compared with adjacent normal lung tissue,the positive expression rate of KIAA1522 protein in NSCLC tissue was significantly increased(P<0.05)and was associated with TNM stage(P<0.01).The Western blotting results showed that compared with normal lung epithelial cells BEAS-2B,the expression levels of KIAA1522 protein in lung cancer cell lines PC9,H1299,H460,A549,H1975,and H226 were significantly increased(P<0.05 or P<0.01).Compared with si-NC group,the expression levels of KIAA1522 protein in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the expression level of KIAA1522 protein in the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01).The MTT results showed that at 24,48,and 72 h of cell culture,compared with si-NC group,the proliferation activities of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the proliferation activity of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.05);compared with OE-KIAA1522 group,the proliferation activity of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the proliferation activity of the A549 cells in MK2206 group was significantly decreased(P<0.05).The cell scratch assay results showed that compared with si-NC group,the migration rates of the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the migration rate of the A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the migration rate of the A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.05);compared with OE-KIAA1522+MK2206 group,the migration rate of the A549 cells in MK2206 group was significantly decreased(P<0.05).The Transwell chamber assay results showed that compared with si-NC group,the numbers of invasion H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.01);compared with OE-NC group,the number of invasion A549 cells in OE-KIAA1522 group was significantly increased(P<0.01);compared with OE-KIAA1522 group,the number of invasion A549 cells in OE-KIAA1522+MK2206 group was significantly decreased(P<0.01);compared with OE-KIAA1522+MK2206 group,the number of invasion A549 cells in MK2206 group was significantly decreased(P<0.01).The Western blotting results showed that compared with si-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the H1299 cells in KIAA1522-siRNA#1 group and KIAA1522-siRNA#2 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.01);compared with OE-NC group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522 group were significantly increased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly decreased(P<0.05);compared with OE-KIAA1522 group,the expression levels of p-AKT,Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in OE-KIAA1522+MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05);compared with OE-KIAA1522+MK2206 group,the expression levels of Cyclin D1,Vimentin,N-cadherin,and VEGF proteins in the A549 cells in MK2206 group were significantly decreased(P<0.05 or P<0.01),while the expression level of E-cadherin protein was significantly increased(P<0.05).Conclusion:The KIAA1522 protein upregulates the expression of Cyclin D1,EMT-related proteins,and VEGF protein in lung cancer cells,promoting the proliferation,migration,and invasion of lung cancer cells,and its mechanism is related to the activation of the AKT signaling pathway.

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Objective:To analyze the real-world practices of resecting sessile colorectal polyps of varying long diameters using cold forcep polypectomy (CFP), cold snare polypectomy (CSP), or endoscopic mucosal resection (EMR).Methods:A total of 12 290 nonpedunculated colorectal polyps of long diameter ≤19 mm (from 10 295 patients) were retrospectively enrolled from January 2022 to December 2023. Polypectomy was conducted by 30 endoscopists. The polyps were categorized into three groups based on long diameter: 1-5 mm, >5-10 mm and >10-19 mm, and the differences of polypectomy methods were compared in three groups. The usage of hemostatic clips in CSP among >5-10 mm polyps and the changes in resection methods between 2022 and 2023 were analyzed.Results:CFP (6 769 polyps, 81.7%) was the predominant method for resecting 1-5 mm sessile polyps (8 289 polyps). For sessile polyps sized >5-10 mm (2 455 polyps), CSP was used most (1 372, 55.9%), although its utilization varied significantly among physicians with the median usage rate of 52.9% (40.3%, 60.0%). EMR (1 349 poolyps, 87.3%) was the main method for >10-19 mm sessile polyps. The usage rate of CSP in sessile polypectomy for polyps >5-10 mm significantly increased from 45.7% (503/1 101) in 2022 to 64.2% (869/1 354) in 2023. The overall frequency of using clip in CSP for >5-10 mm sessile polyps was 40.1% (550/1 372), demonstrating notable variability among different endoscopists with median usage rate of 48.3% (29.8%, 67.9%).Conclusion:Varied resection methods are observed among endoscopists for sessile polyps measuring ≤19 mm. CFP is primarily utilized for polyps of 1-5 mm, while CSP is favored for polyps >5-10 mm, with an increasing annual usage rate. EMR is the main approach for the polyps >10-19 mm. Additionally, notable variations in the use of metal clips during CSP are observed among different physicians.