OBJECTIVE To establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

Objective To investigate the effects of DNA demethylation drugs combined with histone deacetylase in-hibitors on fragile X mental retardation 1 neighbor protein (FMR1NB) expression and its promoter methylation in human oral cancer cells and try to find a strategy of weakening the heterogeneity of FMR1NB expression.Methods Human oral cancer cell lines Cal27 and SCC-9 were treated with decitabine (DAC) , an inhibitor of DNA meth-yltransferase, combined with trichostatin A (TSA) and valproic acid (VPA), inhibitors of histone deacetylase.Then reverse transcription-polymerase chain reaction (RT-PCR) , quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of FMR1 NB and pyrosequencing was used to detect the methylation of FMR1NB promoter.Results Compared with the blank control group, DAC and its combination with TSA and VPA significantly induced the expression of FMR1NB mRNA and protein in Cal27 and SCC-9 cells.Compared with DAC alone group, FMR1NB mRNA expression of each DAC-combined drug groups significantly increased, but FMR1NB protein did not significantly change in Cal27 cells; for SCC-9 cells, except for DAC+TSA group, the mRNA and protein levels of FMR1NB significantly increased in all other groups.In addition, there was no signifi-cant difference in the expression of FMR1 NB mRNA and protein between the three-combined drugs group and two-combined drugs groups.Further methylation assay showed that the methylation level of the overall FMR1NB promot-er and its each CpG site measured were reduced to varying degrees in all treatment groups except for three-combina-tion drug group of SCC-9.Conclusion DAC and its combination with TSA and VPA can enhance the expression of FMR1NB by mediating the demethylation of FMR1NB promoter, wherein the enhanced expression effect of the com-bination of the two drugs is stronger, suggesting that they have the potential to weaken the heterogeneity of FMR1NB expression and improve the immunotherapy effect of oral cancer.

Objective To explore the construction of a core competency framework and content for higher vocational speech-lan-guage-hearing rehabilitation technology programs based on World Health Organization rehabilitation competency framework(RCF). Methods Utilizing RCF and integrating the educational objectives for higher vocational speech-language-hearing reha-bilitation programs outlined by the Ministry of Education in 2022,as well as the technical documents from the In-ternational Association of Logopedics and Phoniatrics and the American Speech-Language-Hearing Association,this study analyzed the professional activities in speech-language-hearing rehabilitation technology to construct a competency framework based on RCF and give details in the specific content of each domain. Results The competency for speech-language-hearing rehabilitation technology encompassed seven domains:core val-ues,beliefs,practice,professionalism,learning and development,management and leadership,and research.Each domain was subdivided into specific competency elements and professional activities. Conclusion Establishing a higher vocational education system for speech-language-hearing rehabilitation technology based on RCF will help to set educational objectives,and construct curriculum systems,so that to cultivate practi-tioner who meet social needs and possess comprehensive professional skills and competencies.

Objective To investigate the serological changes of blood type and whether hemolytic reactions occurred in a patient with ABw subtype after type A therapeutic plasma exchange(TPE)retrospectively.Methods The ABO blood group identification and genotyping was carried out by microcolumn gel method,microcolumn glass bead method,saline tube method and absorption-elution test,and the laboratory results before and after TPE were analyzed.Results The patient un-derwent 2 000 mL type A TPE in other hospitals and was transferred to our hospital.On the second day of hospitalization,the test showed consistency between forward and reverse blood typing.On the third day,the detection showed that Bc was±～1+,and discrepancy was found between forward and reverse typing.The presence of B antigen was confirmed through tube method and human anti-B absorption-elution test,and was identified as ABw03 by molecular biological method.After type A TPE,Hb and Plt both temporarily decreased,creatinine slightly increased,ALT and AST continued to decrease,while TBIL,DBIL and IBIL showed a temporary decrease followed by an increase,indicating a slight hemolytic reaction.Conclu-sion Infusion of large volume of plasma may cause hemolytic reactions when ABO subtype patients contain weak A or B an-tigens.The blood type should be strictly identified according to the ABO blood type forward and reverse typing standards.Ad-ditional laboratory tests combined with molecular biology techniques are required for weak agglutination,which can reduce the missed detection of ABO subtypes and reduce the occurrence of transfusion reactions.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Objective To explore the value of combined detection of lipoprotein-associated phospholipase A2(Lp-PLA2),neuron specific enolase(NSE)and S-100 calcium binding protein β(S-100β)in the diagnosis and prognosis evaluation of acute cerebral infarction(ACI)in patients with carbon monoxide poisoning(CMP).Methods A total of 102 patients with CMP complicated with ACI admitted to the hospital from Jan-uary 2020 to November 2021 were selected as the study group,meanwhile,102 patients with simple CMP were enrolled as the control group.Patients in the study group were followed up for 6 months after discharge,ac-cording to the follow-up results,they were grouped into good prognosis group(60 cases)and poor prognosis group(42 cases).The serum levels of Lp-PLA2,NSE and S-100β were detected by enzyme-linked immunosor-bent assay(ELISA).The receiver operating characteristic(ROC)curve was applied to analyze the value of the combination of serum Lp-PLA2,NSE and S-100β in the early diagnosis and prognosis evaluation of patients with CMP and ACI.Results Compared with the control group,the levels of Lp-PLA2,NSE and S-100β in the study group were obviously higher(P<0.05).The ROC curve analysis results showed that the area under the curve(AUC)of the combined detection of serum Lp-PLA2、NSE、S-100β for the diagnosis of CMP complicat-ed with ACI was greater than the AUC of single detection of each indicator(P<0.001).Compared with the good prognosis group,the levels of Lp-PLA2,NSE and S-100β in the poor prognosis group were obviously higher(P<0.05).The results of ROC curve analysis showed that the AUC of the combined detection of ser-um Lp-PLA2、NSE、S-100β for the prognosis of patients with CMP complicated with ACI was greater than the AUC of single detection of each indicator(P<0.05).Conclusion The expression of Lp-PLA2,NSE and S-100β in serum of patients with CMP complicated with ACI is high,and the combined detection of the three has certain value in the diagnosis and prognosis evaluation for patients with CMP complicated with ACI.