OBJECTIVE To comprehensively assess the rationality and safety of clinical application of ceftazidime-avibactam(CAZ/AVI)so as to provide bases for reasonable and safe application of the drugs.METHODS A total of 137 patients who were hospitalized in Tianjin First Central Hospital and were treated with CAZ/AVI from Jan.2023 to Jan.2024 were recruited as the research subjects.The relevant informations involving the baseline da-ta,infection sites,etiological tests,status of drug utilization and adverse reactions were investigated and statically analyzed.The rating form was designed based on relevant guideline consensus and package insert,and the rational-ity and safety of clinical application of days were evaluated.RESULTS Totally 137 valid cases were enrolled in the study,88(64.23％)of whom were male,and 49(35.77％)were female,with the mean age(52±21.89)years old and the average medication duration(12.2±6.45)days.Totally 79 case-times of drug administration were un-reasonable,involving 75 patients;unsuited indications,unreasonable treatment course,absence of special consul-tation and ward round records and no curative effect evaluation after drug administration for 48-72 hours were the major manifestations.The total effective rate of CAZ/AVI treatment was 87.62％,5 patients had CAZ/AVI-associated adverse reactions,with the incidence of adverse reactions 3.65％.CONCLUSION It is necessary for the hospital to further standardize and optimize the clinical utilization of CAZ/AVI,strictly conform to the medica-tion indications,and strengthen the medication surveillance so as to raise the rationality and safety of medication.

Objective To evaluate the application of novel oral anticoagulants(NOACs)in the treatment of elderly patients with non-valvular atrial fibrillation(NVAF),and to provide a basis for the rational use of drugs in clinical practice.Methods Based on the Beers criteria(2023 edition),combined with drug instructions and relevant guidelines,the potential inappropriate medication(PIM)evaluation criteria of NOACs in NVAF patients were formulated.The medication PIM of patients aged 80 years or older who were hospitalized in the cardiovascular department from January to December 2023 was analyzed when using NOACs.Results A total of 78 cases were included,and 47 cases of PIM occurred in NOACs,including 1 case of renal function-related PIM(2.13％),and 46 cases of drug interaction related PIM(97.87％).There were 72 patients who do not meet the evaluation criteria of the 2023 version of the Beers standard.Conclusion The updated Beers standard has not yet been widely adopted in clinical practice.The highest incidence of PIM in the use of NOACs in elderly patients with NVAF is due to drug interactions.It is necessary to strengthen drug monitoring in elderly patients with NVAF and promote rational drug use.

Objective To evaluate the application of novel oral anticoagulants(NOACs)in the treatment of elderly patients with non-valvular atrial fibrillation(NVAF),and to provide a basis for the rational use of drugs in clinical practice.Methods Based on the Beers criteria(2023 edition),combined with drug instructions and relevant guidelines,the potential inappropriate medication(PIM)evaluation criteria of NOACs in NVAF patients were formulated.The medication PIM of patients aged 80 years or older who were hospitalized in the cardiovascular department from January to December 2023 was analyzed when using NOACs.Results A total of 78 cases were included,and 47 cases of PIM occurred in NOACs,including 1 case of renal function-related PIM(2.13％),and 46 cases of drug interaction related PIM(97.87％).There were 72 patients who do not meet the evaluation criteria of the 2023 version of the Beers standard.Conclusion The updated Beers standard has not yet been widely adopted in clinical practice.The highest incidence of PIM in the use of NOACs in elderly patients with NVAF is due to drug interactions.It is necessary to strengthen drug monitoring in elderly patients with NVAF and promote rational drug use.

Objective:To address the critical issue of missing dynamic border molding information in edentulous direct digital impression technology, this study explores innovative digital solutions and conducts preliminary application validation.Methods:Based on the myostatic line theory, a methodology was established: intraoral scanner (IOS) high-frequency video was utilized to dynamically capture functional molding data of soft tissues, integrated with a self-developed mobility gradient recognition algorithm to achieve dynamic threshold segmentation between the muscle dynamic zone and myostatic zone, termed "optical digital molding technology". Ten edentulous patients with well-fitting complete dentures, treated at the Department of Prosthodontics, Peking University School and Hospital of Stomatology from January 2024 to December 2024, were enrolled. The standard deviation between the muscle static line (generated by mobility gradient algorithm with thresholds of 0.3-0.7 mm) and the denture border curve was analyzed to optimize the dynamic threshold, followed by single-case clinical validation.Results:Among the mobility thresholds of 0.3-0.7 mm, the 0.5 mm threshold yielded the smallest standard deviation between the myostatic line and denture border. Clinical validation demonstrated that dentures designed with this threshold exhibited no displacement during dynamic functional tests, with marginal sealing meeting clinical standards.Conclusions:The optical digital border molding technique for edentulous soft tissue boundaries translates the myostatic line theory into quantifiable parameters for the first time. Based on data from 10 cases, a mobility threshold of 0.5 mm is recommended for clinical application.

Objective:To analyze the expression level of protein arginine methyltransferase 5 (PRMT5) in pancreatic cancer tissues and its correlation with prognosis using bioinformatics methods, and to explore its potential mechanisms.Methods:Expression analysis of the PRMTs family members was performed based on the gene expression profiles of 178 pancreatic cancer tissues from the Gene Expression Profiling Interactive Analysis (GEPIA) database and 171 normal pancreatic tissues from the TCGA and GTEx databases. Using the median expression level of PRMTs family members in pancreatic cancer tissues as the cutoff, patients were divided into high-expression and low-expression groups, and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) were plotted. The correlation between PRMT5 expression and the expression of oncogenes such as KRAS, TP53, BRCA1, BRCA2, and SLC39A4 was analyzed. Functional enrichment analysis was conducted on genes similar to PRMT5, and a protein-protein interaction (PPI) network was constructed to analyze the interaction relationships among these similar genes. Pancreatic cancer PANC1 and AsPC-1 cells cultured in standard medium served as the control group, while PANC1 and AsPC-1 cells cultured in medium supplemented with the PRMT5 inhibitor EPZ015666 served as the intervention group. Cell viability was assessed using the CCK-8 assay, and cell cycle progression was analyzed by flow cytometry.Results:The expression level of PRMT5 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues and showed a significant negative correlation with both OS and DFS. Patients with high PRMT5 expression had a shorter median survival time compared to those with low expression (17.2 months vs 19.5 months). PRMT5 expression was significantly positively correlated with the expression of oncogenes KRAS, TP53, BRCA1, BRCA2, SLC39A4, and KLF5. Genes similar to PRMT5 were primarily enriched in cell cycle-related signaling pathways, and NOP58 identified as a hub gene in the PPI network. Compared to the control group, the proliferation activity of PANC1 and AsPC-1 cells in the intervention group was significantly reduced [(67.3±1.9)% vs (100±4.4)% for PANC1; (60.5±2.7)% vs (100.0±1.7)% for AsPC-1], and the proportion of cells in the G1 phase was significantly increased [(51.6±0.7)% vs (35.3±2.7)% for PANC1; (51.2±0.9)% vs (29.7±2.2)% for AsPC-1]. All these differences were statistically significant (all P values <0.05). Conclusions:High expression of PRMT5 was closely associated with poor prognosis in pancreatic cancer patients, and it may contribute to pancreatic cancer progression by regulating the cell cycle.

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.

Objective:To analyze the expression level of protein arginine methyltransferase 5 (PRMT5) in pancreatic cancer tissues and its correlation with prognosis using bioinformatics methods, and to explore its potential mechanisms.Methods:Expression analysis of the PRMTs family members was performed based on the gene expression profiles of 178 pancreatic cancer tissues from the Gene Expression Profiling Interactive Analysis (GEPIA) database and 171 normal pancreatic tissues from the TCGA and GTEx databases. Using the median expression level of PRMTs family members in pancreatic cancer tissues as the cutoff, patients were divided into high-expression and low-expression groups, and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) were plotted. The correlation between PRMT5 expression and the expression of oncogenes such as KRAS, TP53, BRCA1, BRCA2, and SLC39A4 was analyzed. Functional enrichment analysis was conducted on genes similar to PRMT5, and a protein-protein interaction (PPI) network was constructed to analyze the interaction relationships among these similar genes. Pancreatic cancer PANC1 and AsPC-1 cells cultured in standard medium served as the control group, while PANC1 and AsPC-1 cells cultured in medium supplemented with the PRMT5 inhibitor EPZ015666 served as the intervention group. Cell viability was assessed using the CCK-8 assay, and cell cycle progression was analyzed by flow cytometry.Results:The expression level of PRMT5 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues and showed a significant negative correlation with both OS and DFS. Patients with high PRMT5 expression had a shorter median survival time compared to those with low expression (17.2 months vs 19.5 months). PRMT5 expression was significantly positively correlated with the expression of oncogenes KRAS, TP53, BRCA1, BRCA2, SLC39A4, and KLF5. Genes similar to PRMT5 were primarily enriched in cell cycle-related signaling pathways, and NOP58 identified as a hub gene in the PPI network. Compared to the control group, the proliferation activity of PANC1 and AsPC-1 cells in the intervention group was significantly reduced [(67.3±1.9)% vs (100±4.4)% for PANC1; (60.5±2.7)% vs (100.0±1.7)% for AsPC-1], and the proportion of cells in the G1 phase was significantly increased [(51.6±0.7)% vs (35.3±2.7)% for PANC1; (51.2±0.9)% vs (29.7±2.2)% for AsPC-1]. All these differences were statistically significant (all P values <0.05). Conclusions:High expression of PRMT5 was closely associated with poor prognosis in pancreatic cancer patients, and it may contribute to pancreatic cancer progression by regulating the cell cycle.

Objective To investigate the effect of ginsenoside Re on angiotensin Ⅱ(Ang Ⅱ)-induced proliferation,migration,and phenotype transformation of vascular smooth muscle cells(VSMCs)by regulating the Ras homologous gene family member A(RhoA)/mitogen activated protein kinase(MAPK)pathway.Methods MOVAS cells were divided into control group,Ang Ⅱ group,ginsenoside Re low dose group,ginsenoside Re medium dose group,ginsenoside Re high dose group,andginsenoside Re high dose+RhoA activator(U46619)group.MOVAS cell proliferation was detected by CCK-8.MOVAS cell migration was detected by scratch assay.Immunocytochemistry was used to detect the positive expression of α-smooth muscle actin(α-SMA)and osteopontin(OPN)proteins in MOVAS cells.qRT-PCR was used to detect the mRNA expression of PCNA,MMP-9,and MMP-2 in MOVAS cells.Western blot was used to detect RhoA,phosphorylated extracellular signal regulated kinase 1/2(p-ERK1/2),phosphorylated stress activated protein kinase 1(p-JNK1),and p-P38 protein in MOVAS cells.Results Compared with the control group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,RhoA,p-ERK1/2,p-JNK1,p-P38 protein expression of MOVAS cells in the Ang II group increased,while the positive expression of α-SMA protein decreased significantly(P<0.05).Compared with the Ang Ⅱ group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,and RhoA,p-ERK1/2,p-JNK1,and p-P38 proteins of MOVAS cells in the low,medium,and high dose groups of ginsenoside Re decreased,while the positive expression of α-SMA protein increased.The trend was most significant in the high dose group of ginsenoside Re(P<0.05).Compared with ginsenoside Re high-dose group,OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression and RhoA,p-ERK1/2,p-JNK1,p-P38 protein in ginsenoside Re high-dose+U46619 group increased,the positive expression of α-SMA protein decreased significantly(P<0.05).Conclusion Ginsenoside Re may inhibit the proliferation,migration,and phenotype transformation of Ang Ⅱ in MOVAS cells by suppressing the RhoA/MAPK pathway.

Objective To investigate the effect of ginsenoside Re on angiotensin Ⅱ(Ang Ⅱ)-induced proliferation,migration,and phenotype transformation of vascular smooth muscle cells(VSMCs)by regulating the Ras homologous gene family member A(RhoA)/mitogen activated protein kinase(MAPK)pathway.Methods MOVAS cells were divided into control group,Ang Ⅱ group,ginsenoside Re low dose group,ginsenoside Re medium dose group,ginsenoside Re high dose group,andginsenoside Re high dose+RhoA activator(U46619)group.MOVAS cell proliferation was detected by CCK-8.MOVAS cell migration was detected by scratch assay.Immunocytochemistry was used to detect the positive expression of α-smooth muscle actin(α-SMA)and osteopontin(OPN)proteins in MOVAS cells.qRT-PCR was used to detect the mRNA expression of PCNA,MMP-9,and MMP-2 in MOVAS cells.Western blot was used to detect RhoA,phosphorylated extracellular signal regulated kinase 1/2(p-ERK1/2),phosphorylated stress activated protein kinase 1(p-JNK1),and p-P38 protein in MOVAS cells.Results Compared with the control group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,RhoA,p-ERK1/2,p-JNK1,p-P38 protein expression of MOVAS cells in the Ang II group increased,while the positive expression of α-SMA protein decreased significantly(P<0.05).Compared with the Ang Ⅱ group,the OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression,and RhoA,p-ERK1/2,p-JNK1,and p-P38 proteins of MOVAS cells in the low,medium,and high dose groups of ginsenoside Re decreased,while the positive expression of α-SMA protein increased.The trend was most significant in the high dose group of ginsenoside Re(P<0.05).Compared with ginsenoside Re high-dose group,OD450 value,scratch healing rate,OPN protein positive expression,PCNA,MMP-9,MMP-2 mRNA expression and RhoA,p-ERK1/2,p-JNK1,p-P38 protein in ginsenoside Re high-dose+U46619 group increased,the positive expression of α-SMA protein decreased significantly(P<0.05).Conclusion Ginsenoside Re may inhibit the proliferation,migration,and phenotype transformation of Ang Ⅱ in MOVAS cells by suppressing the RhoA/MAPK pathway.

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.