Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

OBJECTIVE: To study the durability of the anti-demineralization effects of fluoride varnish after being applied to dental root surfaces. METHODS: Coronal and radicular dentin samples were prepared from extracted human teeth. Duraphat^® (DP) was applied to the dentine surfaces to form a protective film. The film-dentin interfaces were observed by scanning electron microscopy (SEM) and the fluoride element was analyzed with energy dispersive spectrometer (EDS). Thus, the differences between applying DP on crowns and roots were compared. Radicular dentin samples were prepared and randomly divi-ded into four groups: (1) Blank: DP was not applied, and demineralized in acetic acid (pH 4.5) for 4 days; (2) Blank+aging: DP was not applied, the samples were put into deionized water for 14 days at room temperature, and then demineralized in acetic acid (pH 4.5) for 4 days; (3) DP: DP was applied and demineralized in acetic acid (pH 4.5) for 4 days; (4) DP+aging: DP was applied, the samples were put into deionized water for 14 days at room temperature, and then demineralized in acetic acid (pH 4.5) for 4 days. Finally, SEM observation and EDS analysis of fluoride content were performed on film-dentin interfaces to evaluate the degree of demineralization, the morphology of DP film, and the penetration of fluorine. RESULTS: The immediate penetration depth of fluoride element from DP was deeper in the coronal dentin than that in radicular dentin. The samples in the blank and blank+aging groups demine-ralized significantly after acid etching. The DP group did not undergo demineralization, and the fluorine element penetrated to (76.00±8.94) μm below the interfaces. The structure of the protective film in the DP+aging group was damaged, but the underneath dentin did not undergo demineralization. The fluorine element still remained at a depth of (5.00±3.53) μm below the interfaces. CONCLUSION DP has an anti-demineralization effect on the root surface, and this effect can still be exerted for a period of time after losing the structure of protective film. It has the ability to prevent root caries and a certain durability.
Humans ; Tooth Root/drug effects* ; Fluorides, Topical/pharmacology* ; Tooth Demineralization/prevention & control* ; Dentin/drug effects* ; Fluorides ; In Vitro Techniques ; Cariostatic Agents/pharmacology*

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.

Occupational noise-induced hearing loss (NIHL) is an irreversible sensorineural hearing loss that severely endangers workers’ health, making early screening crucial. This article reviewed the research progress on early screening methods for occupational NIHL, introduced the testing mechanisms of three core screening methods—tympanometry, otoacoustic emissions, and extended high-frequency audiometry —and summarized their clinical application advantages and limitations. It is proposed that multimodal combined detection (e.g., the combination of tympanometry, otoacoustic emissions, and extended high-frequency audiometry) can significantly improve the accuracy and comprehensiveness of early screening. Meanwhile, future studies with prospective cohort design are encouraged to verify the long-term monitoring value of each method and to strengthen the joint development of screening technologies with cutting-edge approaches such as machine learning, in order to further improve screening efficiency and provide stronger protection for workers’ hearing health.

OBJECTIVE To explore the effect and safety of dapagliflozin on cardiac function and renal function， blood glucose， and quality of life in patients with heart failure （HF） combined with chronic kidney disease （CKD）. METHODS A total of 156 patients with HF combined with CKD admitted to Shangqiu First People’s Hospital from January 1， 2021 to January 1， 2023 were included. According to the random number table， the patients were randomly divided into conventional treatment group （n＝80） and dapagliflozin group （n＝76）. Conventional treatment group was given conventional treatment； dapagliflozin group was additionally given Dapagliflozin tablets 10 mg orally， once a day， based on conventional treatment group. Both groups were treated for 6 months. Cardiac function [left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， N-terminal pro-brain natriuretic peptide （NT-proBNP）]， renal function [blood creatinine， urea nitrogen， urinary albumin excretion rate （UAER）， glomerular filtration rate （GFR）， creatinine 806731979@qq.com clearance rate （CCR）]， glycosylated hemoglobin， and the quality of life were observed in 2 groups before and after treatment. The occurrence of ADR was recorded. RESULTS After treatment， LVESD， LVEDD， NT-proBNP， blood creatinine， urea nitrogen， UAER in 2 groups as well as the level of glycosylated hemoglobin in dapagliflozin group were significantly lower than before treatment； the dapagliflozin group was significantly lower than the conventional treatment group. LVEF， GFR， CCR and Kansas City Cardiomyopathy Questionnaire score were significantly higher than before treatment， and the dapagliflozin group was significantly higher than the conventional treatment group （P＜0.05）. There was no statistical significance in glycosylated hemoglobin of conventional treatment group before and after treatment （P＞ 0.05）. There was no statistically significant difference in the incidence of dizziness， rash， liver dysfunction， urinary system infection， new dialysis and hypotension between the two groups （P＞0.05）. CONCLUSIONS Dapagliflozin can improve the cardiac function and renal function of patients with HF complicated with CKD， improve patients’ quality of life and lower blood sugar levels without increasing the risk of adverse events.

Objective:To explore the relationship between fluid dosage during fluid resuscitation and the risk of disseminated intravascular coagulation(DIC)in postpartum hemorrhage patients.Methods:A retrospective case-control study was conducted on patients who were admitted to Shenyang Women′s and Children′s Hospital between January 1,2016,and December 31,2022 with postpartum hemorrhage≥1000 ml.The patients were di-vided into two groups according to pregnancy-corrected ISTH scores:group with ISTH score＞26;group with ISTH score≤26.The two groups were matched for 1 ∶ 4 propensity scores and the differences between ratio of crystalloid solution to bleeding volume;ratio of colloidal solution to bleeding volume;ratio of red blood cell infusion to bleeding volume;ratio of plasma infusion to bleeding volume and peak decrease of fibrinogen in the two groups were compared.And analyze the relationship between various observation indicators and the occurrence of DIC.Results:The ROC area under the curve(AUC)values for predicting of the ratio of crystalloid solution to bleeding volume,ratio of colloidal solution to bleeding volume,the peak decrease in fibrinogen,ratio of red blood cell infu-sion to bleeding volume,ratio of plasma infusion to bleeding volume were 0.670(95%CI 0.589-0.751),0.532(95%CI 0.440-0.623),0.771(95%CI 0.706-0.837),0.530(95%CI 0.439-0.621),and 0.563(95%CI 0.473-0.653),the optimal cut off values were 1.23,0.29,0.77,0.48,0.24.The ratio of crystalloid solution to bleeding volume and the peak decrease in fibrinogen were positively correlated with the occurrence of DIC after postpartum hemorrhage,the OR values were 0.256(95%CI 0.111-0.590)and 0.074(95%CI 0.024-0.228).There was no correlation between the ratio of colloidal solution to bleeding volume,the ratio of red blood cell infusion to bleeding volume,the ratio of plasma infusion to bleeding volume and the occurrence of DIC after postpartum hemorrhage.Conclusions:The infusion volume of crystalloid solution is related to the occurrence of DIC,and restrictive fluid resuscitation can reduce the incidence of DIC.Additionally,to lower the risk of DIC,fibrin-ogen or cold precipitation should be rapidly supplied when the decrease of fibrinogen exceeded 0.77 g/L to re-duce the risk of postpartum hemorrhage DIC.

BACKGROUND:In the process of exploring the mechanism of Alzheimer's disease,the important role of bioinformatics for common target screening has been revealed,enabling the use of its screening results as a basis for exploring the therapeutic effects of drugs on the disease. OBJECTIVE:To predict the targets of liraglutide,a glucagon-like peptide-1 receptor agonist,in the treatment of Alzheimer's disease by bioinformatics and molecular biology. METHODS:DisGeNET database and SEA database were used to obtain the common genes of Alzheimer's disease and liraglutide.GO/KEGG enrichment analysis of common targets was conducted using DAVID online database.Protein-protein interaction networks were constructed using STRING database.The optimal dosage of liraglutide was determined using cell counting kit-8 assay.Expression of key proteins was analyzed using immunofluorescence and immunoblotting techniques.The mouse hippocampal neuron HT22 cell line was used for ex vivo experiments,and the cells were randomly divided into three groups:HT22 group,HT22+Aβ group,and HT22+Aβ+Lir group.No special treatment was done in the HT22 group,while Aβ1-42 was used to intervene in the HT22 cell line for 24 hours to construct an Aβ injury cell model in the HT22+Aβ group.In additional to modeling,liraglutide was added to the HT22+Aβ+Lir group for 12 hours. RESULTS AND CONCLUSION:A total of 3 333 genes associated with Alzheimer's disease were screened from DisGeNET database.Then 147 potential targets of liraglutide were obtained from SEA database.Finally,64 common targets of Alzheimer's disease and Liraglutide were determined using R packets.GO/KEGG analysis of common targets using DAVID online database suggested that common targets were mainly enriched in the following biological processes:neuroactive ligand-receptor interaction,renin-angiotensin system,bladder cancer,endopeptidase activity,peptide receptor activity,G protein-coupled peptide receptor activity,and transport vesicles.The obtained 64 common target proteins were imported into SRTING online database for protein-protein interaction network construction,and the top three genes,matrix metalloproteinases 2,9 and interleukin 1β,were obtained.The activity of cultured cells was detected by the cell counting kit-8 kit.Liraglutide at 100 nmol/L was the optimal concentration for antagonizing Aβ1-42.In the western blot and immunofluorescence assays,the expression of matrix metalloproteinases 2,9 and interleukin 1β was significantly increased in the HT22+Aβ group compared with the HT22 group(P＜0.05)but significantly decreased in the HT22+Aβ+Lir group compared with the HT22+Aβ group(P＜0.05).To conclude,the above bioinformatics data and secondary validation of differential genes in the GEO database suggest that both matrix metalloproteinases 2,9 and interleukin 1β could be potential targets of liraglutide in the treatment of Alzheimer's disease.

BACKGROUND:Studies have found that glucagon-like peptide-1 and its analogues have a significant neuroprotective effect,and some drugs have been applied to the clinical stage Ⅲ study of Alzheimer's disease.However,the mechanism of its neuroprotective effect is still unclear,which needs to be further explored and clarified. OBJECTIVE:To screen out the genes related to the pathogenesis of Alzheimer's disease and the related targets of semaglutide for the treatment of Alzheimer's disease based on bioinformatics and network pharmacology analyses,to identify the potential target genes by comprehensive analysis of the two and to verify them at the cellular level. METHODS:Using DisGeNET database,differentially expressed genes between Alzheimer's disease patients and healthy population were screened out.The chemical structure formula and two-dimensional structure diagram of semaglutide were obtained using PubChem online database.GO/KEGG enrichment analysis was performed using DAVID online database.A protein-protein interaction network was constructed by using the STRING database.The HPA database was used to determine the distribution characteristics of the target proteins in various human tissues.Finally,western blot was used to detect relevant protein expression in HT22 cells after semaglutide intervention. RESULTS AND CONCLUSION:With the dataset in DisGeNET database,3 374 differentially expressed genes between Alzheimer's disease patients and healthy people were obtained,and meanwhile,101 target genes of semaglutide potential drugs were obtained.There were 23 intersection genes between them.Ten key genes were identified based on the protein-protein interaction network,which were silent information regulator 1(SIRT1),CASP9,CCND1,CASP1,KEAP1,DLG4,CASP4,GRB2,GRIA1,and EDNRA.The results of GO gene functional annotation analysis of key genes showed that the positive regulatory activity of cysteine endopeptidase,the positive regulation of proteolysis,and the positive regulation of cysteine endopeptidase involved the cytoplasmic part of the apoptotic activity process;AMPA glutamate receptor complex,inflammatory complex,CARD domain binding,cysteine endopeptidase activity,and cysteine endopeptidase activity were involved in the apoptotic process.The results of KEGG signaling pathway analysis indicated that colorectal cancer,non-small cell carcinoma,and endometrial carcinoma were related to immune infiltration,inflammation and autophagic apoptosis.In addition,according to the association ranking of key genes and their distribution in different tissues of HPA online database,SIRT1 was identified as the most significant differential gene.The expression level of SIRT1 protein was significantly down-regulated in HT22 cells after β-amyloid protein 1-42 treatment,but it could be significantly increased after being treated with semaglutide.To conclude,SIRT1 may be a target gene for semaglutide in the treatment of Alzheimer's disease.

Objective:To identify the independent factors of unplanned interruption during continuous renal replacement therapy (CRRT) and construct a risk prediction model, and to verify the clinical application effectiveness of the model.Methods:A retrospective study was conducted on critically ill adult patients who received CRRT treatment in the intensive care unit (ICU) of Zhejiang Hospital from January 2021 to August 2022 for model construction. According to whether unplanned weaning occurred, the patients were divided into two groups. The potential influencing factors of unplanned CRRT weaning in the two groups were compared. The independent influencing factors of unplanned CRRT weaning were screened by binary Logistic regression and a risk prediction model was constructed. The goodness of fit of the model was verified by a Hosmer-Lemeshow test and its predictive validity was evaluated by receiver operator characteristic curve (ROC curve). Then embed the risk prediction model into the hospital's ICU multifunctional electronic medical record system for severe illness, critically ill patients with CRRT admitted to the ICU of Zhejiang Hospital from November 2022 to October 2023 were prospectively analyzed to verify the model's clinical application effect.Results:① Model construction and internal validation: a total of 331 critically ill patients with CRRT were included to be retrospectively analyzed. Among them, there were 238 patients in planned interruption group and 93 patients in unplanned interruption group. Compared with the planned interruption group, the unplanned interruption group was shown as a lower proportion of males (80.6% vs. 91.6%) and a higher proportion of chronic diseases (60.2% vs. 41.6%), poor blood purification catheter function (31.2% vs. 6.3%), as a higher platelet count (PLT) before CRRT initiation [×10 9/L: 137 (101, 187) vs. 109 (74, 160)], lower level of blood flow rate [mL/min: 120 (120, 150) vs. 150 (140, 180)], higher proportion of using pre-dilution (37.6% vs. 23.5%), higher filtration fraction [23.0% (17.5%, 32.9%) vs. 19.1% (15.7%, 22.6%)], and frequency of blood pump stops [times: 19 (14, 21) vs. 9 (6, 13)], the differences of the above 8 factors between the two groups were statistically significant (all P < 0.05). Binary Logistic regression analysis showed that chronic diseases [odds ratio ( OR) = 3.063, 95% confidence interval (95% CI) was 1.200-7.819], blood purification catheter function ( OR = 4.429, 95% CI was 1.270-15.451), blood flow rate ( OR = 0.928, 95% CI was 0.900-0.957), and frequency of blood pump stops ( OR = 1.339, 95% CI was 1.231-1.457) were the independent factors for the unplanned interruption of CRRT (all P < 0.05). These 4 factors were used to construct a risk prediction model, and ROC curve analysis showed that the area under the curve (AUC) predicted by the model was 0.952 (95% CI was 0.930-0.973, P = 0.003 0), with a sensitivity of 88.2%, a specificity of 89.9%, and a maximum value of 1.781 for the Youden index. ② External validation: prospective inclusion of 110 patients, including 63 planned interruption group and 47 unplanned interruption group. ROC curve analysis showed that the AUC of the risk prediction model was 0.919 (95% CI was 0.870-0.969, P = 0.004 3), with a sensitivity of 91.5%, a specificity of 79.4%, and a maximum value of the Youden index of 1.709. Conclusion:The risk prediction model for unplanned interruption during CRRT has a high predictive efficiency, allowing for rapid and real-time identification of the high risk patients, thus providing references for preventative nursing.

Objective:To explore the mediating effect of distress disclosure between perceived social support and psychological distress in colorectal cancer patients.Methods:The convenient sampling method was used to select 220 postoperative colorectal cancer patients who were reviewed in China-Japan Union Hospital of Jilin University from February to August 2023 as the research objetcs. The Distress Disclosure Index (DDI), Perceived Social Support Scale (PSSS), and Chinese version of Screening Tool for Psychological Distress in Cancer Patients were used to conduct the survey.Results:A total of 220 questionnaires were distributed in this study, and 213 valid questionnaires were recovered, with a valid recovery rate of 96.82%. The total score of the Chinese version of Screening Tool for Psychological Distress in Cancer Patients for colorectal cancer patients was (4.31±2.46), the total score of the DDI was (37.26±9.97), and the total score of the PSSS was (57.82±14.60). Pearson correlation analysis showed that psychological distress was negatively correlated with distress disclosure in colorectal patients ( P<0.01), distress disclosure was positively correlated with perceived social support ( P<0.01), and psychological distress was negatively correlated with perceived social support ( P<0.01). The mediating effect results showed that the direct effect of perceived social support on psychological distress was -0.359 ( P<0.01), and the mediating effect between perceived social support and psychological distress was -0.227 ( P<0.01), which acted as a partial mediating effect with the mediating effect accounting for 38.74% of the total effect. Conclusions:Perceived social support can not only directly affect the psychological distress of colorectal cancer patients, but also indirectly affect psychological distress through distress disclosure. Clinical staffs should take certain interventions to improve the level of patients' perceived social support and distress disclosure, so as to improve the psychological distress of patients.