OBJECTIVE To investigate the effect and mechanism of bumetanide on lung injury in chronic obstructive pulmonary disease （COPD） model rats. METHODS COPD rat model was induced by lipopolysaccharide， and they were randomly divided into model group （COPD group）， bumetanide low-dose and high-dose groups （Bumetanide-L group， Bumetanide-H group）， bumetanide high-dose+Yes-associated protein/transcriptional coactivator containing PDZ-binding motif （YAP/TAZ） signaling pathway activator group （Bumetanide-H+PY-60 group）， with 12 rats in each group. Another 12 normal rats were selected as normal control group （Control group）. Thirty minutes before modeling， bumetanide/normal saline was inhaled or/and PY-60/ normal saline was injected into the tail vein. On the next day after the completion of modeling and drug administration， the pulmonary function index of the rats in each group was measured [forced expiratory volume in 0.3 seconds （FEV0.3）， forced vital capacity （FVC）， peak expiratory flow （PEF）， FEV0.3/FVC]. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in bronchoalveolar lavage fluid （BALF） were determined； the pathological morphology of lung tissue and degree of pulmonary fibrosis were observed. The expression levels of transforming growth factor- β （TGF- β）， α -smooth muscle actin （α-SMA） and TAZ protein as well as the phosphorylation of YAP protein in lung tissues were detected. RESULTS Compared with COPD group， the pathological injury of lung tissue in Bumetanide-L and Bumetanide-H groups was alleviated； the exfoliation of lung epithelial cells， tube wall thickening and the degree of pulmonary fibrosis were alleviated； inflammatory cell infiltration was reduced， and blue collagen deposition was reduced； FEV0.3， FVC， FEV0.3/FVC and PEF were significantly increased， while the lung injury score， levels of TNF-α， IL-6， IL-1β， expression levels of TGF-β， α-SMA and TAZ protein and the phosphorylation of YAP protein were significantly decreased （P＜0.05）. PY-60 could significantly reverse the improvement effects of bumetanide on above indexes （P＜0.05）. CONCLUSIONS Bumetanide can alleviate lung injury， inflammatory response and pulmonary fibrosis in COPD rats， and its mechanism is related to inhibiting YAP/TAZ signaling pathway.

Objective To evaluate five types of DIC scoring systems based on sepsis patients,to explore the values of different DIC scoring systems in the occurrence and prognosis of DIC in sepsis patients,and to compare the applicability of different DIC scoring systems for sepsis complicated with DIC.Methods Laboratory indexes and clinical data from sepsis patients who had been hospitalized in Gansu Provincial People's Hospital from December 1,2019 to December 31,2021 were retrospectively analyzed within 24 hours.Five types of DIC scoring systems were used to score,and the difference of diagnostic rate and discharge outcome in sepsis patients with different severity was compared.The ROC curves of five DIC scoring systems were established to evaluate the accu-racy of DIC in sepsis patients.Results The fatality rate of sepsis increased with the severity of sepsis(P<0.05).There were statistically significant differences in discharge outcomes between DIC and non-DIC in the five scoring systems(P<0.05).JMHW,CDSS and part of ISTH were detected in JAAM cases,while ISTH was detected in non-dominant ISTH cases.ISTH,JAAM,JMHW,CDSS,and non-dominant ISTH5 scoring systems were used to diagnose DIC,and absence of full health restoration and death were 3.0,3.8,4.2,3.9,and 3.0 times higher than non-DIC cases,respectively.Conclusion JAAM scoring system has higher diagnostic rate and sensitivity for adult sepsis.CDSS and JMHW scoring systems are more accurate in predicting the prognosis of sepsis patients.

Objective: To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge (S. miltiorrhiza, Dan Shen) and C. tinctorius L. (C. tinctorius, Hong Hua) as an herb pair through network pharmacology and subsequent experimental validation. Methods: Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of S. miltiorrhiza and C. tinctorius as herb pair. Molecular docking was used to verify the binding of the components of these herbs and their potential targets. An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects, which were evaluated using the combination index. Western blot was performed to detect the protein expression of these targets. Results: Network pharmacology analysis revealed 5 pathways and 8 core targets of S. miltiorrhiza and C. tinctorius in myocardial protection. Five of the core targets were enriched in the hypoxia-inducible factor-1 (HIF-1) signaling pathway. S. miltiorrhiza-C. tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway. As an upstream gene of the HIF-1 pathway, STAT3 can be activated by the active ingredients cryptotanshinone (Ctan), salvianolic acid B (Sal. B), and myricetin (Myric). Cell experiments revealed that Myric, Sal. B, and Ctan also exhibited synergistic myocardial protective activity. Molecular docking verified the strong binding of Myric, Sal. B, and Ctan to STAT3. Western blot further showed that the active ingredients synergistically upregulated the protein expression of STAT3. Conclusion The pharmacodynamic transmission analysis revealed that the active ingredients of S. miltiorrhiza and C. tinctorius can synergistically resist ischemia through various targets and pathways. This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

BACKGROUND: Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1). METHODS: The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group. RESULTS: Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05). CONCLUSIONS FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Dual Specificity Phosphatase 1/pharmacology* ; Cell Proliferation ; p38 Mitogen-Activated Protein Kinases/pharmacology* ; Methylation ; Apoptosis ; Cell Line, Tumor

OBJECTIVE To analyze the use status and development trend of proton pump inhibitors(PPIs) in 33 hospitals in Wuhan, Hubei Province after the implementation of the national centralized drug procurement(NCDP) policy, and to provide reference for promoting the subsequent rational use of NCDP drugs and improving related policies. METHODS To make statistics and analysis of purchasing amount of PPIs, defined daily dose system(DDDs), defined daily dose consumption(DDDc) and utilization rate of 33 hospitals in Wuhan in 2019 and 2022. RESULTS After the implementation of the NCDP policy, the total purchasing amount of PPIs decreased by 53.6%, DDDs decreased by 15.4%, DDDc decreased by 45.2%, and the utilization rate of PPIs injectable dosage forms decreased by 12.6%. After NCDP, the highest growth rate of oral dosage forms was omeprazole(5.7%), followed by rabeprazole(5.0%), while injectable dosage forms showed a significant difference in utilization rate, with a significant decline in NCDP varieties and a significant increase in non-NCDP varieties. The overall NCDP utilization rate of PPIs in Wuhan was 64.9%, with little difference among hospitals of different grades. CONCLUSION The NCDP policy achieves the purpose of reducing the drug cost of patients and improving the accessibility of drugs, and is more optimized in the selection of dosage forms, which is in line with the policy expectations overall; but the quantity and price of PPIs in Wuhan decreased after NCDP, and highlighted a certain tendency in the selection of varieties. In the future, we still need to optimize measures to guide clinical priority in the selection of NCDP drugs, to ensure and improve the implementation of NCDP policy.

BACKGROUND:There is an internal relationship between hyperhomocysteinemia and vascular calcification.However,the pathogenesis of hyperhomocysteinemia promoting vascular calcification is still unclear. OBJECTIVE:To investigate the role of bone morphogenetic protein-2 in hyperhomocysteinemia-induced vascular calcification. METHODS:Human carotid wax samples were divided into a calcified group(n=29)and a non-calcified group(n=13)according to the presence or absence of calcified plaque.Sixteen ApoE-/-mice were randomly divided into a control group and a hyperhomocysteinemia group,with 8 mice in each group.Bone morphogenetic protein-2 vector was used to transfect rat thoracic artery smooth muscle A7r5 cells,and gradient concentration of homocysteine(50,100,200,and 400 μmol/L)was utilized to treat A7r5 cells.Calcification was detected by alizarin red staining and hematoxylin-eosin staining.The interaction of bone morphogenetic protein 2 with Runt-related transcription factor 2 was detected by immunofluorescence,and the expressions of bone morphogenetic protein 2,Runt-related transcription factor 2,and α-smooth muscle actin were detected by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION:(1)Human carotid artery tissue staining revealed that compared with the non-calcification group,inflammatory cells increased and calcification positive rate increased in the calcification group(P<0.05).Compared with the non-calcification group,the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated,and the expression of α-smooth muscle actin was decreased in the calcification group(all P<0.05).(2)The staining of mouse arterial specimens exhibited that,the positive rate of calcified area in the hyperhomocysteinemia group was significantly higher than that in the control group(P<0.05);serum homocysteine level in the hyperhomocysteinemia group was significantly higher than that in the control group(P<0.05).Compared with the control group,the expressions of bone morphogenetic protein-2 and Runt-related transcription factor 2 were up-regulated,and the expression of α-smooth muscle actin was decreased in the hyperhomocysteinemia group(all P<0.05).(3)A7r5 cell culture analysis demonstrated that with the increase of homocysteine concentration gradient,the degree of calcification,the content of bone morphogenetic protein-2 and Runt-related transcription factor 2 protein in A7r5 cells increased(P<0.05),and the content of α-smooth muscle actin protein decreased(P<0.05).(4)The A7r5 cell culture analysis of overexpressed bone morphogenetic protein 2 showed that the calcification degree of the overexpressed bone morphogenetic protein 2 group was increased compared with the corresponding control group,the β-sodium glycerophosphate group,and the homocysteine group.RUNt-related transcription factor 2 expression up-regulated(P<0.05)and α-smooth muscle actin expression down-regulated(P<0.05).(5)The expression of bone morphogenetic protein 2 increased in A7r5 cells cultured with homocysteine in calcified medium,and the expression of Runt-related transcription factor 2 increased with the increase of bone morphogenetic protein 2 expression.(6)The results confirm that bone morphogenetic protein-2 is a key target gene in the regulation of smooth muscle cell phenotypic transformation resulting in vascular calcification by hyperhomocysteinemia.Targeted regulation of bone morphogenetic protein-2 reduces hyperhomocysteinemia-induced vascular calcification.

Objective:To analyze the implementation effects of a medical laboratory talent training program based on local colleges and universities' applied talent-oriented cultivation principal as well as students' interests and industry needs.Methods:Based on the design principals of clarifying the professional orientation, meeting the national standard, reconstructing the curriculum system, introducing the spirit of innovation and entrepreneurship, and multi-dimensional collaborative education, as well as the reverse design path of the outcome-based education concept, we have built a medical laboratory applied talent training system focusing on humanity education, solid foundation, broad employment, and good competency and in accordance with the "three complete education" strategy, along with measures including creating an applied teaching atmosphere, developing an applied curriculum teaching model, providing vocational guidance and improving vocational identity, and promoting education via evaluation. The system was applied to the training and practice of students of grades 2021 and 2022 majoring in medical laboratory technology. SPSS20.0 software was used for statistical analysis.Results:With the concept of application-oriented talent training and the "four-in-one" practical teaching model, students' skills were improved, and the training path was broadened. Compared with those trained with the original program (grades 2019-2020), the graduates trained with the new program (grades 2021-2022) showed a significantly decreased employment rate in medical laboratory jobs in medical institutions from 71.25% to 42.86% ( χ2=12.36, P<0.001), a significantly increased employment rate in in-vitro diagnostics industry from 3.75% to 17.14% ( χ2=7.44, P<0.05), and a significantly increased rate of applying for postgraduate education from 17.05% to 32.86% ( χ2=4.74, P<0.05). Conclusions:The medical laboratory talent training program based on the talent training principal of local colleges and universities combined with students' interests and industry needs can help improve the quality of talent training and broaden the employment path of graduates.

Objective:To investigate the internal structure and determinants of hospitalization expenses for uterine leiomyoma patients in DRG pilot and non-DRG pilot hospitals in Beijing,to fumish insights for the forthcoming phase of public hospital reform.Methods:The statistical data of 5 DRG pilot hospitals and 124 non-DRG pilot hospitals in Beijing from 2015 to 2021 were collected to analyze the correlation degree between each detail expense and the average hospitalization expense by using grey correlation analysis,and the influencing factors of the average hospitalization expense of hospitalized patients by using random forest model.Results:The results of the grey correlation analysis revealed that the highest correlations affecting hospitalization expense in the DRG pilot hospital group and the non-DRG pilot hospital group were the average expense in each surgical treatment and the average drug costs for each patient,respectively,and the lowest was the average expense of inspection and test in each patient.The results of random forest model showed that the top two influencing factors of DRG pilot hospital group were consumption ratio and the average length of hospitalization,while the average length of hospitalization,surgical treatment expense ratio and consumption ratio are more important than other influential factors of non-DRG pilot hospital group.Conclusion:DRG payment is conducive to optimizing the hospitalization expense structure of uterine leiomyoma hospitalized patients.The average length of hospitalization,consumption ratio,and surgical treatment expense ratio are important factors affecting the hospitalization expense of uterine leiomyoma hospitalized patients.Public hospitals should continue to optimize the expense structure in the future,pay equal attention to"reducing expenditure"and"open source",implement DRG payment and its supporting measures to enhance the efficiency of medical services,reinforce the comprehensive management of consumables,and empower hospitals and medical personnel.

Objective:To investigate the internal structure and determinants of hospitalization expenses for uterine leiomyoma patients in DRG pilot and non-DRG pilot hospitals in Beijing,to fumish insights for the forthcoming phase of public hospital reform.Methods:The statistical data of 5 DRG pilot hospitals and 124 non-DRG pilot hospitals in Beijing from 2015 to 2021 were collected to analyze the correlation degree between each detail expense and the average hospitalization expense by using grey correlation analysis,and the influencing factors of the average hospitalization expense of hospitalized patients by using random forest model.Results:The results of the grey correlation analysis revealed that the highest correlations affecting hospitalization expense in the DRG pilot hospital group and the non-DRG pilot hospital group were the average expense in each surgical treatment and the average drug costs for each patient,respectively,and the lowest was the average expense of inspection and test in each patient.The results of random forest model showed that the top two influencing factors of DRG pilot hospital group were consumption ratio and the average length of hospitalization,while the average length of hospitalization,surgical treatment expense ratio and consumption ratio are more important than other influential factors of non-DRG pilot hospital group.Conclusion:DRG payment is conducive to optimizing the hospitalization expense structure of uterine leiomyoma hospitalized patients.The average length of hospitalization,consumption ratio,and surgical treatment expense ratio are important factors affecting the hospitalization expense of uterine leiomyoma hospitalized patients.Public hospitals should continue to optimize the expense structure in the future,pay equal attention to"reducing expenditure"and"open source",implement DRG payment and its supporting measures to enhance the efficiency of medical services,reinforce the comprehensive management of consumables,and empower hospitals and medical personnel.

Objective:To investigate the internal structure and determinants of hospitalization expenses for uterine leiomyoma patients in DRG pilot and non-DRG pilot hospitals in Beijing,to fumish insights for the forthcoming phase of public hospital reform.Methods:The statistical data of 5 DRG pilot hospitals and 124 non-DRG pilot hospitals in Beijing from 2015 to 2021 were collected to analyze the correlation degree between each detail expense and the average hospitalization expense by using grey correlation analysis,and the influencing factors of the average hospitalization expense of hospitalized patients by using random forest model.Results:The results of the grey correlation analysis revealed that the highest correlations affecting hospitalization expense in the DRG pilot hospital group and the non-DRG pilot hospital group were the average expense in each surgical treatment and the average drug costs for each patient,respectively,and the lowest was the average expense of inspection and test in each patient.The results of random forest model showed that the top two influencing factors of DRG pilot hospital group were consumption ratio and the average length of hospitalization,while the average length of hospitalization,surgical treatment expense ratio and consumption ratio are more important than other influential factors of non-DRG pilot hospital group.Conclusion:DRG payment is conducive to optimizing the hospitalization expense structure of uterine leiomyoma hospitalized patients.The average length of hospitalization,consumption ratio,and surgical treatment expense ratio are important factors affecting the hospitalization expense of uterine leiomyoma hospitalized patients.Public hospitals should continue to optimize the expense structure in the future,pay equal attention to"reducing expenditure"and"open source",implement DRG payment and its supporting measures to enhance the efficiency of medical services,reinforce the comprehensive management of consumables,and empower hospitals and medical personnel.