Based on the target recognition ability of split aptamer and intelligent analytical capability of molecular logic gate,in this work,two split aptamers were integrated into"AND"logic gate to construct a novel ortho-nucleic acid fluorescence sensor for simultaneous detection of thrombin and myoglobin.When there was one target,the response of the signal was only a single fluorescence output signal,which was used as an evaluation standard for early low-risk judgment.When two targets coexisted,the split aptamer bound to the target to form a ternary complex and led to the head and tail ortho-nucleic acid effect respectively,and triggered the G4 chain to enhance the fluorescence signal of thioflavin T and the fluorescence signal quenching of Cyanine 3,which could be used as an evaluation criterion for early high-risk judgement.Under the optimal conditions,the linear range for detection of thrombin was 3-200 nmol/L,with a correlation coefficient of 0.9931 and a detection limit of 0.97 nmol/L,and the linear range for detection of myoglobin was 6-400 nmol/L,with a correlation coefficient of 0.9933,and a detection limit of 2.14 nmol/L.The method was applied to simultaneous determination of thrombin and myoglobin in clinical serum samples,and the recoveries were 85.4%-118.3%and 85.8%-119.9%,respectively,with relative standard deviations of less than 6.5%.Compared with the standard method,the relative error range was from-8.8%to 5.6%.In addition,the logical diagnosis results of 4 serum samples were high-risk of acute myocardial infarction in 2 cases and low-risk in 2 cases.The ″AND″ logic gate ortho-nucleic acid fluorescence sensing method showed many advantages such as high selectivity,rapidity,accuracy and simultaneous detection,which offered important reference for early diagnosis of acute myocardial infarction,and also provided a general detection design strategy and platform for simultaneous detection of biomarkers.

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

The rise of nanomedicine has opened up new avenues for drug delivery and tumor treatment.Nanocarriers,in particular,have become core tools in the field of drug delivery.Anti-cancer peptides(ACPs)can achieve anti-tumor effects by inducing tumor cell apoptosis,inhibiting angiogenesis,and regulating the immune microenvironment.Their low toxic side effects and drug resistance make them im-portant in the field of cancer treatment.However,ACPs face limitations such as poor stability,short in vivo half-life,and low targeted delivery efficiency,which seriously limit their therapeutic effects and fur-ther development.Nanocarriers provide an efficient,flexible and precise solution for the delivery of ACPs due to their advantages of increasing drug solubility,changing drug distribution in the body and improving drug targeting.This review systematically summarizes the structural characteristics and biological proper-ties of four types of nanocarriers,including liposome nanocarriers,polymer nanocarriers,inorganic nano-carriers,and self-assembled peptides,and focuses on analyzing the application examples of nanocarriers in enhancing the stability of ACPs,improving targeted delivery efficiency,improving bioavailability,and overcoming drug-resistant tumor treatment.We also summarize in detail the structural pros and cons of these four carriers.Finally,we look forward to the development direction of research on the combination of nanocarriers and ACPs,in order to provide a theoretical basis for the clinical application of ACPs.

Objective To explore the factors influencing the blood concentration of voriconazole in elderly hospitalized patients and inform the probability of attaining the target concentration in clinical practice.Methods Patients aged ≥65 years who were hospitalized in the First Affiliated Hospital of Anhui Medical University from January 2022 to December 2023 and underwent voriconazole blood concentration monitoring were enrolled.Their voriconazole blood concentrations and clinical data were collected.The patients were grouped according to the target effective concentration 0.5-5.0 mg/L of voriconazole recommended by the Chinese Pharmacological Society guidelines.Multivariate logistic regression analysis was used to determine the factors affecting the rate of achieving the target concentration.Results The 202 enrolled patients included 139 males and 63 females.A total of 244 voriconazole blood concentrations were available.The median age of the patients was 74(range:65-95)years.Voriconazole blood concentration ranged from 0.08 to 13.38 mg/L.The average concentration was(4.10±2.45)mg/L.The target effective blood concentration of voriconazole was achieved in 65.35％(132/202)of the patients.Logistic regression results showed that the dosage regimen,body weight,and hypoproteinemia(albumin＜25 g/L)were the main factors affecting voriconazole blood concentration.Conclusions The dosing regimen,body weight,and hypoproteinemia are the main influencing factors of voriconazole blood concentration.Relevant factors should be fully considered in clinical medication to ensure the safety and effectiveness of voriconazole.

Aim To investigate the changes in hepatic lactylation during liver regeneration and its impact on regeneration.Methods A partial hepatectomy(PHx)mouse model was used to study liver regenera-tion.Sodium oxamate was administered intraperitoneal-ly to inhibit lactate dehydrogenase,and blood and liver tissues were collected at different time points post-sur-gery.The histopathological status was observed using HE staining.Proliferating cell nuclear antigen(PC-NA)levels were detected by immunohistochemistry.Lactylation was assessed using immunofluorescence.Liver LDH enzyme activity,lactate levels and serum alanine aminotransferase(ALT)and aspartate trans-aminase(AST)levels were measured using assay kits.Results After PHx,the liver volume of mice gradual-ly increased,returning to preoperative size on day 7.PCNA levels peaked at 48 hours post-surgery.Liver tissue lactate levels increased to approximately 1.5 times the preoperative level at 12 hours post-surgery and remained elevated until day 7.The lactylation lev-el in hepatocytes peaked at 24 hours post-surgery,gradually declined after 48 hours,and returned to pre-operative levels on day 7.Compared to the PHx group,the sodium oxamate(750 mg·kg-1)+PHx group showed significantly reduced lactylation levels in hepa-tocytes and a smaller liver regeneration volume on day 7.Conclusion Lactylation regulates hepatocyte pro-liferation and promotes liver regeneration after PHx.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Aim To investigate the changes in hepatic lactylation during liver regeneration and its impact on regeneration.Methods A partial hepatectomy(PHx)mouse model was used to study liver regenera-tion.Sodium oxamate was administered intraperitoneal-ly to inhibit lactate dehydrogenase,and blood and liver tissues were collected at different time points post-sur-gery.The histopathological status was observed using HE staining.Proliferating cell nuclear antigen(PC-NA)levels were detected by immunohistochemistry.Lactylation was assessed using immunofluorescence.Liver LDH enzyme activity,lactate levels and serum alanine aminotransferase(ALT)and aspartate trans-aminase(AST)levels were measured using assay kits.Results After PHx,the liver volume of mice gradual-ly increased,returning to preoperative size on day 7.PCNA levels peaked at 48 hours post-surgery.Liver tissue lactate levels increased to approximately 1.5 times the preoperative level at 12 hours post-surgery and remained elevated until day 7.The lactylation lev-el in hepatocytes peaked at 24 hours post-surgery,gradually declined after 48 hours,and returned to pre-operative levels on day 7.Compared to the PHx group,the sodium oxamate(750 mg·kg-1)+PHx group showed significantly reduced lactylation levels in hepa-tocytes and a smaller liver regeneration volume on day 7.Conclusion Lactylation regulates hepatocyte pro-liferation and promotes liver regeneration after PHx.

Objective To explore the factors influencing the blood concentration of voriconazole in elderly hospitalized patients and inform the probability of attaining the target concentration in clinical practice.Methods Patients aged ≥65 years who were hospitalized in the First Affiliated Hospital of Anhui Medical University from January 2022 to December 2023 and underwent voriconazole blood concentration monitoring were enrolled.Their voriconazole blood concentrations and clinical data were collected.The patients were grouped according to the target effective concentration 0.5-5.0 mg/L of voriconazole recommended by the Chinese Pharmacological Society guidelines.Multivariate logistic regression analysis was used to determine the factors affecting the rate of achieving the target concentration.Results The 202 enrolled patients included 139 males and 63 females.A total of 244 voriconazole blood concentrations were available.The median age of the patients was 74(range:65-95)years.Voriconazole blood concentration ranged from 0.08 to 13.38 mg/L.The average concentration was(4.10±2.45)mg/L.The target effective blood concentration of voriconazole was achieved in 65.35％(132/202)of the patients.Logistic regression results showed that the dosage regimen,body weight,and hypoproteinemia(albumin＜25 g/L)were the main factors affecting voriconazole blood concentration.Conclusions The dosing regimen,body weight,and hypoproteinemia are the main influencing factors of voriconazole blood concentration.Relevant factors should be fully considered in clinical medication to ensure the safety and effectiveness of voriconazole.

The rise of nanomedicine has opened up new avenues for drug delivery and tumor treatment.Nanocarriers,in particular,have become core tools in the field of drug delivery.Anti-cancer peptides(ACPs)can achieve anti-tumor effects by inducing tumor cell apoptosis,inhibiting angiogenesis,and regulating the immune microenvironment.Their low toxic side effects and drug resistance make them im-portant in the field of cancer treatment.However,ACPs face limitations such as poor stability,short in vivo half-life,and low targeted delivery efficiency,which seriously limit their therapeutic effects and fur-ther development.Nanocarriers provide an efficient,flexible and precise solution for the delivery of ACPs due to their advantages of increasing drug solubility,changing drug distribution in the body and improving drug targeting.This review systematically summarizes the structural characteristics and biological proper-ties of four types of nanocarriers,including liposome nanocarriers,polymer nanocarriers,inorganic nano-carriers,and self-assembled peptides,and focuses on analyzing the application examples of nanocarriers in enhancing the stability of ACPs,improving targeted delivery efficiency,improving bioavailability,and overcoming drug-resistant tumor treatment.We also summarize in detail the structural pros and cons of these four carriers.Finally,we look forward to the development direction of research on the combination of nanocarriers and ACPs,in order to provide a theoretical basis for the clinical application of ACPs.

Objective To investigate the effects of low background radiation environments in deep underground settings on the biological behavior of NP69 human nasopharyngeal epithelial cells(NP69 cells)and the underlying molecular mechanisms.Methods A parallel control experimental design was adopted and NP69 cells were synchronously cultured in settings of three underground depths at the China in situ Deep-Underground Facility&Life Observatory(DeUFO)—ground level(DeUFO-0 m),1 000 m underground(DeUFO-1 000 m),and 1 500 m underground(DeUFO-1 500 m).Changes in cell proliferation and migration capabilities were assessed using the Cell Counting Kit-8(CCK-8)assay and scratch assay,respectively.High-throughput RNA sequencing(RNA-Seq)was performed to identify differentially expressed genes(DEGs).Functional annotation and pathway enrichment analysis of the DEGs were performed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.Results CCK-8 assay revealed that,after 72 h of culture,the absorbance value of the DeUFO-0 m group was 1.35 times and 1.27 times those of the those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).After 96 h of culture,the absorbance value of the DeUFO-0 m group was 1.52 times and 1.41 times those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).Colony formation assays revealed that the number of cell colonies in the DeUFO-0 m group was 1.59 times and 1.27 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.001).The scratch assay revealed that the 36-hour wound healing rate of the DeUFO-0 m group was 2.22 times and 4.00 times those of the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transwell assays revealed that the number of migrating cells in the DeUFO-0 m group was 2.08 times and 2.56 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transcriptome sequencing analysis revealed consistent upregulation of CELF2,CELF4,CGB8,GRHL2,and DMRTA2 genes in the DeUFO-1 000 m and DeUFO-1 500 m groups.Pathway enrichment analysis indicated significant enrichment of extracellular matrix(ECM)remodeling-associated pathways and gene expression regulation pathways in the experimental groups(false discovery rate[FDR]<0.05).Conclusion The low background radiation environment in deep underground settings suppresses the proliferation and migration activities of NP69 cells by mediating ECM remodeling and post-transcriptional regulatory mechanisms through the regulation of target genes such as the CELF family.This study provides experimental evidence for establishing a dose-response relationship between environmental radiation and cellular effects.