OBJECTIVE To explore the transformation of the dispensing and drug pickup process in traditional Chinese medicine pharmacy （TCM Pharmacy） in our hospital based on data-intelligence-driven， aiming to improve pharmacists’ work efficiency and patients’ drug pickup experience. METHODS Value stream mapping and journey mapping were used to systematically identify non-value-added links in pharmacists’ dispensing process and key pain points in patients’ drug pickup under the traditional process. An intelligent dispensing and drug pickup system for the TCM Pharmacy was developed based on the C# and Android television platforms， and a machine-learning model was adopted to predict patients’ drug pickup waiting time. A comprehensive evaluation was performed from three perspectives： system performance， prediction accuracy， and satisfaction of pharmacists and patients. RESULTS The system successfully streamlined non-value-added links such as “waiting for writing on the board” and “searching for drugs”， and realized multimodal dynamic prompts of dispensing status through auditory （number calling） and visual （television terminal） channels. The constructed model for predicting drug pickup waiting time exhibited good fitting degree and generalization ability （mean absolute error＝4.28 min， R 2 ＝0.882）. The comprehensive satisfaction scores of pharmacists and patients in the traditional mode were significantly increased from （70.99±1.74） and （73.58±1.98） to （90.02±1.30） and （88.61±2.08） in the new system， respectively （ P ＜0.01）. CONCLUSIONS The transformation of the intelligent drug dispensing and pickup system for TCM pharmacy based on data-intelligence-driven effectively improves the efficiency of pharmacists’ dispensing work， realizes process transparency and waiting time predictability， and significantly enhances patients’ drug pickup experience.

ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma（RH） before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group， model group， lactulose group（1.5 mg·kg^-1）， high， medium and low dose groups of RH and RH steaming with wine（PRH）（8， 4， 1 g·kg^-1）. Except for the control group， the constipation model was replicated by gavage of loperamide hydrochloride（6 mg·kg^-1） in the other groups. After 2 weeks of modeling， each administration group was gavaged with the corresponding dose of drug solution， and the control and model groups were given an equal volume of normal saline， 1 time/d for 2 consecutive weeks. After administration， the feces were collected for 16S rRNA sequencing， the levels of gastrin（GAS）， motilin（MTL）， interleukin-6（IL-6）， γ-interferon（IFN-γ） in the colonic tissue were detected by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of colon were observed by hematoxylin-eosin（HE） staining， flow cytometry was used to detect the proportion changes of CD4⁺， CD8⁺ and regulatory T cell（Treg） in peripheral blood. ResultsCompared with the control group， the model group showed significantly decrease in fecal number in 24 h， fecal quality and fecal water rate（P<0.01）， the colon was seen to have necrotic shedding of mucosal epithelium， localized intestinal glands in the lamina propria were degenerated， necrotic and atrophied， a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner， the contents of GAS and MTL， the proportions of CD4⁺， CD8⁺ and Treg were significantly reduced（P<0.01）， the contents of IL-6 and IFN-γ were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the fecal number in 24 h， fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased（P<0.05， P<0.01）， the pathological damage of the colon was alleviated to varying degrees， the contents of GAS， MTL， IL-6 and IFN-γ were significantly regressed（P<0.05， P<0.01）， and the proportions of CD4⁺ and CD8⁺ were significantly increased（P<0.01）， although the proportion of Treg showed an upward trend， there was no significant difference. In addition， the results of intestinal flora showed that the number of amplicon sequence variant（ASV） and Alpha diversity were decreased in the model group compared with the control group， and there was a significant difference in Beta diversity， with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group， the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH， and there was a trend of regression of Beta diversity to the control group， the relative abundance of Lactobacillus increased， and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis， promote immune system activation， inhibit the release of inflammatory factors for enhancing the gastrointestinal function， which may be one of the potential mechanisms of their therapeutic effect on constipation.

Objective To discuss the application of using transulnar approach(TUA),which is used as a complementary approach,after failure of transradial approach(TRA)in performing neurointerventional surgery,and to evaluate its clinical safety and feasibility.Methods A total of 189 consecutive patients,who were admitted to the Department of Neurointerventional Surgery,Affiliated Hospital of Binzhou Medical University of China from January to August of 2023 to receive treatment,were retrospectively collected.Of the 189 patients receiving neurointerventional surgery using TRA,23 adopted TUA puncture after failure of TRA puncture.The clinical data and the surgical materials were retrospectively collected.The diameter and depth of the radial artery and ulnar artery were measured by Doppler ultrasound before the operation.A 6 F catheter sheath was used to establish intraoperative manipulation access.After treatment,Doppler ultrasonography was used to assess the occurrence of arterial puncture-related complications and the patency of artery.The technical success rate and the puncture-related complications of TUA in neurointerventional surgery were calculated and analyzed.Results All the 23 patients underwent neurointerventional surgery.The preoperative mean ulnar artery diameter of the forearm and the depth of the ulnar radial artery measured by Doppler ultrasound were(2.1±0.3)mm and(5.6±1.0)mm respectively.The success rate of using TUA after failure of TRA for neurointerventional surgery was 91.3％(21/23)and no additional re-disinfection was required during the same procedure.In 2 patients,transfemoral artery approach(TFA)was used after failure of TUA.The causes of TUA failure included failure of guide wire insertion due to repeated puncturing(n=1)and failure of catheterization due to severe pain(n=1).Postoperative forearm angiography with manual-push injection method demonstrated that ulnar artery spasm occurred in S patients(34.8％).Postoperative re-examination of Doppler ultrasonography showed that no diminished pulse of the ulnar artery or hand ischemia was observed.One patient developed fat liquefaction at the puncture site,two patients developed hematoma around the puncture point,and one patient experienced transitory numbness around the puncture point.Thirty days after treatment,the follow-up check with Doppler ultrasonography showed that no ulnar artery occlusion was observed.Conclusion During the performance of neurointerventional surgery,the use of TUA after failure of TRA,which is used as a complementary approach,is clinically safe and feasible.However,because TUA carries several certain technical difficulties such as puncturing,catheterization,deeper position and smaller diameter of ulnar artery,diffuse arterial pulsation,etc.the operators need to go through a long learning curve before his or her puncturing success rate of ulnar artery can be surely improved.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective:To establish reference ranges for left and right ventricular structure and function parameters using cardiovascular magnetic resonance (CMR) in healthy Tibetan natives residing at ultra-high altitudes, and analyze their influencing factors.Methods:This prospective study enrolled Tibetan healthy volunteers who underwent CMR examinations between September 2021 and August 2022. Participants were stratified into four age groups: 20-29, 30-39, 40-49, and 50-59 years. CMR-derived parameters included left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), left/right ventricular end-diastolic volumes (LVEDV/RVEDV), left/right ventricular end-systolic volumes (LVESV/RVESV), and end-diastolic left ventricular mass (LVM at ED). Normally distributed data were compared between genders using independent samples t-test and among age groups using ANOVA. Non-normally distributed data were analyzed with Kruskal-Wallis test. Linear regression assessed relationships between parameters and gender, age, residential altitude, body surface area (BSA), and body mass index (BMI). Results:The study included 66 volunteers (27 males, 39 females), distributed as follows: 21 (20-29 years), 15 (30-39 years), 15 (40-49 years), and 15 (50-59 years). Reference values were: LVEF (62.6±5.7)%, RVEF (55.0±7.1)%, BSA-indexed LVEDV (60.6±12.1)ml/m2, RVEDV (65.5±14.8)ml/m2, LVESV (22.7±5.9)ml/m2, RVESV (29.6±8.1)ml/m2, and LVM at ED (39.1±8.0)g/m2. Gender and age significantly affected RVEF, RVESV, and LVM at ED ( P<0.05). Multivariate regression revealed:Gender independently predicted RVEF ( β=-5.556, P=0.003), RVESV ( β=5.421, P=0.007), and LVM at ED ( β=8.338, P<0.001). Age negatively influenced RVESV ( β=-0.202, P=0.019). BSA positively correlated with LVM at ED ( β=19.980, P=0.041). No significant associations were found with residential altitude or BMI ( P>0.05). Conclusion:This study establishes preliminary reference ranges for ventricular parameters in Tibetan ultra-high altitude natives, with gender, age, and BSA identified as key determinants of cardiac structural/functional indices.

Objective:To evaluate the efficacy and safety of immunotherapy combined with chemotherapy as conversion therapy for initially unresectable locally advanced esophageal squamous cell carcinoma.Methods:This retrospective case series study analyzed clinical and pathological data of 32 patients with initially unresectable locally advanced esophageal squamous cell carcinoma who received immunotherapy combined with chemotherapy at the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University, from June 2020 to December 2024. The cohort included 27 males and 5 females, with an age ( M(IQR)) of 61(9)years (range:46 to 73 years). Five patients were diagnosed with stage Ⅲ, 27 with stage ⅣA. All patients received PD-1 inhibitor sintilimab combined with nedaplatin and albumin-bound paclitaxel. Radiological evaluations were performed every two cycles, the multidisciplinary team evaluation was conducted to determine conversion to resectable status, and patients with successful conversion underwent radical esophagectomy. Follow-up was conducted via telephone or outpatient visits every 3 to 6 months after the last treatment. The primary endpoint was R0 resection rate, secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, major pathological response (MPR) rate, event-free survival (EFS), disease-free survival (DFS) in patients with R0 resection, overall survival (OS) and safety. Kaplan-Meier method was used to plot survival curves and estimate median EFS, DFS, OS rates and their 95% CI. The 95% CI for ORR, pCR rate, MPR rate, and downstaging rate were calculated using the Clopper-Pearson method. Results:The median treatment cycle of 2(1) (range:2 to 8). As of June 2025, the median follow-up was 32.5(13.5)months (range:6.4 to 59.1 months). Among the 32 patients, 9 experienced progression or recurrence, including 2 with liver and lymph node metastases, 2 with lung metastases, 2 with thoracic vertebral metastases, and 3 with mediastinal lymph node metastases. After conversion therapy, 29 patients underwent surgery, achieving an R0 resection rate of 84.4% (95% CI:67.2% to 94.7%), a pCR rate of 27.6% (95% CI:12.7% to 47.2%), and an MPR rate of 55.2% (95% CI:35.7% to 73.6%). Grade 3 or higher surgical complications occurred in 6.9%(2/29) of patients, and grade 3 or higher treatment-related adverse events were observed in 15.6%(5/29). Among the 32 patients, the ORR was 56.3% (95% CI:37.7% to 73.6%),the 3-year EFS rate and OS rate was 59.4% (95% CI:40.8% to 86.4%) and 59.7% (95% CI:40.0% to 89.0%) respectively. Conclusion:Immunotherapy combined with chemotherapy demonstrates high conversion rates and favorable safety in the conversion therapy of initially unresectable locally advanced esophageal squamous cell carcinoma, representing a promising treatment strategy.

Objective To analyze the transcriptome sequencing results of Nelson Bay virus(NBV)-infected murine RAW264.7 mac-rophages,and to screen for differentially expressed genes(DEGs)to provide a theoretical basis for exploring the mechanism of innate immune response in reovirus infection.Methods RAW264.7 cells were infected with the NBV-Miyazaki virus strain at a multiplicity of infection(MOI)of 30.We used transcriptome sequencing technologies,with q＜0.05 and|log2FC|≥ 1,for screening the DEGs in the infection and control groups.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used for enrichment analysis of DEGs.Results A total of 442 genes were differentially expressed in the infection group,of which 381 genes were significantly upregulated and 61 genes were significantly downregulated.In the GO analysis,the enrichment of DEGs was primarily related to the innate immune response,defense response to viruses,cytokine production,and cell response to cytokine stimulation.In the KEGG analysis,the enrichment of DEGs were primarily related to the Toll-like receptor,retinoid acid inducible gene Ⅰ-like receptor,PI3K/Akt,and other signaling pathways.Conclusion RAW264.7 macrophages infected with the NBV-Miyazaki virus can activate pattern recognition receptors;promote the release of cytokines,chemokines,and other immune-related factors;and enhance antibody-dependent cell-mediated cytotoxicity to exert an immune effect.This study provides a theoretical basis for exploring the mechanisms of innate immu-nity during NBV-Miyazaki virus infection.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To analyze the transcriptome sequencing results of Nelson Bay virus(NBV)-infected murine RAW264.7 mac-rophages,and to screen for differentially expressed genes(DEGs)to provide a theoretical basis for exploring the mechanism of innate immune response in reovirus infection.Methods RAW264.7 cells were infected with the NBV-Miyazaki virus strain at a multiplicity of infection(MOI)of 30.We used transcriptome sequencing technologies,with q＜0.05 and|log2FC|≥ 1,for screening the DEGs in the infection and control groups.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases were used for enrichment analysis of DEGs.Results A total of 442 genes were differentially expressed in the infection group,of which 381 genes were significantly upregulated and 61 genes were significantly downregulated.In the GO analysis,the enrichment of DEGs was primarily related to the innate immune response,defense response to viruses,cytokine production,and cell response to cytokine stimulation.In the KEGG analysis,the enrichment of DEGs were primarily related to the Toll-like receptor,retinoid acid inducible gene Ⅰ-like receptor,PI3K/Akt,and other signaling pathways.Conclusion RAW264.7 macrophages infected with the NBV-Miyazaki virus can activate pattern recognition receptors;promote the release of cytokines,chemokines,and other immune-related factors;and enhance antibody-dependent cell-mediated cytotoxicity to exert an immune effect.This study provides a theoretical basis for exploring the mechanisms of innate immu-nity during NBV-Miyazaki virus infection.

Objective:To establish reference ranges for left and right ventricular structure and function parameters using cardiovascular magnetic resonance (CMR) in healthy Tibetan natives residing at ultra-high altitudes, and analyze their influencing factors.Methods:This prospective study enrolled Tibetan healthy volunteers who underwent CMR examinations between September 2021 and August 2022. Participants were stratified into four age groups: 20-29, 30-39, 40-49, and 50-59 years. CMR-derived parameters included left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), left/right ventricular end-diastolic volumes (LVEDV/RVEDV), left/right ventricular end-systolic volumes (LVESV/RVESV), and end-diastolic left ventricular mass (LVM at ED). Normally distributed data were compared between genders using independent samples t-test and among age groups using ANOVA. Non-normally distributed data were analyzed with Kruskal-Wallis test. Linear regression assessed relationships between parameters and gender, age, residential altitude, body surface area (BSA), and body mass index (BMI). Results:The study included 66 volunteers (27 males, 39 females), distributed as follows: 21 (20-29 years), 15 (30-39 years), 15 (40-49 years), and 15 (50-59 years). Reference values were: LVEF (62.6±5.7)%, RVEF (55.0±7.1)%, BSA-indexed LVEDV (60.6±12.1)ml/m2, RVEDV (65.5±14.8)ml/m2, LVESV (22.7±5.9)ml/m2, RVESV (29.6±8.1)ml/m2, and LVM at ED (39.1±8.0)g/m2. Gender and age significantly affected RVEF, RVESV, and LVM at ED ( P<0.05). Multivariate regression revealed:Gender independently predicted RVEF ( β=-5.556, P=0.003), RVESV ( β=5.421, P=0.007), and LVM at ED ( β=8.338, P<0.001). Age negatively influenced RVESV ( β=-0.202, P=0.019). BSA positively correlated with LVM at ED ( β=19.980, P=0.041). No significant associations were found with residential altitude or BMI ( P>0.05). Conclusion:This study establishes preliminary reference ranges for ventricular parameters in Tibetan ultra-high altitude natives, with gender, age, and BSA identified as key determinants of cardiac structural/functional indices.