Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).
Administration, Intravenous ; Administration, Oral ; Animals ; Antihypertensive Agents ; administration & dosage ; blood ; pharmacokinetics ; Apigenin ; administration & dosage ; blood ; isolation & purification ; pharmacokinetics ; Bile ; metabolism ; Chromatography, High Pressure Liquid ; Drug Interactions ; Erigeron ; chemistry ; Glucuronates ; administration & dosage ; blood ; isolation & purification ; pharmacokinetics ; Male ; Metabolic Clearance Rate ; Multidrug Resistance-Associated Proteins ; metabolism ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Valsartan ; administration & dosage ; blood ; pharmacokinetics

Objective To understand the pathogen detection of hospitalized patients before antimicrobial therapy in a hospital through implementation of comprehensive intervention measures,and provide reference basis for the de-velopment of targeted measures.Methods Hospitalized patients who received therapeutic antimicrobial agents in this hospital were selected as the research subjects.Patients who were hospitalized from January to May 2022 were selected as the pre-intervention group,comprehensive intervention measures were taken from June to October 2022,and those who were hospitalized from November 2022 to March 2023 were selected as the post-intervention group.The pathogen detection rate before antimicrobial therapy,sterile specimen detection rate,antimicrobial use rate,de-tection rate of key multidrug-resistant organisms of patients before and after the intervention were analyzed.Results Compared to before intervention,the proportion of pathogen detection rate before antimicrobial therapy(62.09％vs 74.04％),detection rate of healthcare-associated infection diagnosis-related pathogens(62.82％vs 92.73％),and sterile specimen detection rate(35.17％vs 41.06％)of hospitalized patients after intervention all increased signifi-cantly,with statistically significant differences(all P＜0.05).After intervention,pathogen detection rate before the combination use of key antimicrobial agents was not statistically different from before intervention(93.33％vs 90.48％,P＞0.05),while antimicrobial use rate was lower than before intervention(39.93％vs 44.95％,P＜0.05).There was no statistically significant difference in the detection rate of key multidrug-resistant organisms be-fore and after intervention(all P＞0.05).Conclusion Adopting scientific and rational intervention measures can improve the pathogen detection rate,provide a reference basis for the rational use of antimicrobial agents.There was no significant improvement in the pathogen detection rate before the combination use of key antimicrobial agents and the detection rate of key multidrug-resistant organisms,indicating that relevant measures still need to be further optimized.

OBJECTIVETo discuss and analyze the feasibility and strategy for perform the newborn gene screening in the process of newborn hearing screening in order to supply the defects or limitation in the hearing screening.

METHODSFour hundreds and sixty newborn babies from December 2006 to April 2007 accepted the simultaneous hearing and gene screening. Otoacoustic emission (OAE) was used for the first step hearing screening and OAE combined with auto auditory brainstem response (AABR) detection for the second step screening. Newborn genetic disease screening cards were used for collecting the blood spot from the umbilical cord within the moment of newborn. The cards could be directly performed the polymerase chain reaction (PCR) for screening the mitochondrial 12SrRNA 1555G and GJB2 as well as SLC26A4 genes mutations. The restriction enzyme Alw26I was used to recognize the point mutation of 12SrRNA A1555G. The samples with the possible 12SrRNA A1555G mutation were then sequenced to verify. The PCR products from the GJB2 coding region and SLC26A4 IVS7-2A > G hot spot region were sequenced directly. The software of DNAStar was used to analysis the sequence.

RESULTSThe first step of hearing screening of 460 newborn babies showed " refer" on the left ear of nine babies and on the right ear of three babies. Seven showed "refer" on bilateral with the the total of babies 19. After 42 days, they accepted the second step for hearing screening. 16 of the 19 were showed "pass" with OAE and AABR. One baby showed "pass" on the left ear, "refer" on the right ear with the OAE detection but bilateral "pass" with AABR. Two babies failed to accept the re-examination. The newborn gene screening showed five of the 460 babies had the positive response on the A1555G restriction enzyme assay. Of the five babies, one was proved to be the 12SrRNA A1555G mutation and three were the C1556T mutations and one sequence was normal. For the SLC26A4 gene screening, five were the heterozygote of IVS7-2A > G mutation were found and one was carrier the polymorphism of IVS7-18T > G and another was IVS6-62_63insGT heterozygote carrier. For the GJB2 gene screening, eight were 235delC heterozygote carriers, four were G109A heterozygote carriers. All the gene screening found 23 newborn babies of the 460 harbored the changes in the three genes. Of those, one was the 12SrRNA A1555G. pathogenic mutation and 13 were pathogenic heterozygote carriers, nine were the polymorphisms. It was worth to pay more attentions that A1555G mutation was found in the baby whose hearing screening was "pass" in the hearing screening as well as the 13 heterozygote carrier for GJB2 and SLC26A4 gene.

CONCLUSIONSIt might be one of the powerful strategy for adding the concept of newborn gene screening into the hearing screening for the purpose of early diagnosis and discovery the prelingual or late-onset or the high risk as well as the pathogenic carriers. On the basis of the research progress, it was necessary to develop the national newborn gene screening into the process of newborn hearing screening.

Connexins ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Disorders ; diagnosis ; genetics ; prevention & control ; Hearing Tests ; Humans ; Infant, Newborn ; Male ; Neonatal Screening ; Point Mutation

OBJECTIVETo investigate the prevalence of the mitochondrial DNA (mtDNA) A1555G mutation in nonsyndromic hearing impairment (NSHI) patients from Gansu province.

METHODSSubjects included 802 students selected from five Deaf-Mute Schools in Gansu. DNA was extracted from peripheral blood of all patients. The mitochondrial DNA target fragments were amplified by polymerase chain reaction (PCR). The Mutations were detected by AIw26I digestion and sequence analysis.

RESULTSThe homoplasmic A1555G mutation was found in 67 individuals from 802 patients (8.4%). Fifteen of these 67 patients had family histories.

CONCLUSIONSThe mtDNA A1555G mutation had a higher incidence in Gansu population with nonsyndromic hearing impairment than other studies. The data not only gaven more evidences that the prevalence of mtDNA A1555G mutation in china was higher than that in Europe and America, but also gaven valuable information for gene diagnosis, genetic counseling and would improve the safety of aminoglycoside antibiotic therapy.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; DNA, Mitochondrial ; genetics ; Deafness ; genetics ; Female ; Humans ; Male ; Mutation ; Young Adult

OBJECTIVETo investigate the genetic etiologies in the 0- 3-years-old infants with hearing loss and to analyze the interaction between genetics and environmental factors.

METHODSTotal of 130 infants were performed detailed audiological evaluation as well as the detection of the popular deafness gene mutations in GJB2 gene, SLC26A4 and mtDNA12SrRNA. Of them, 84 cases were performed the computer tomography or magnetic resonance imaging examinations.

RESULTSOf the 130 cases, 54 infants were diagnosed as large vestibular aqueduct syndrome, while seven of 130 were as auditory neuropathy and the others were diagnosed as sensorineural hearing loss. Considering of the risks of etiologies for hearing loss, 85 of them had the experiences of the high risk factors at birth (65.4%, 85/130), while 23 of them had the exposure of aminoglycoside antibiotics, and 13 had the family history background as well as two cases were from the consanguineous families. In the causative genes screening, 42 infants were caused by the mutations of SLC26A4 gene (32.3%), but 14 infants found the mutations in GJB2 gene (4.6%), and no infants carried the mutation in mtDNA 12SrRNA 1555G and 1494T points in our studies.

CONCLUSIONSIn our studies, about 36.9% infants hearing loss cases can be found the mutations in SLC26A4 and GJB2 genes. It is essential to put the idea into the hearing evaluation combined with genetic testing for the diagnoses of hearing loss. It is also helpful for exploring the etiologies of hearing loss and performing the target genetic consulting for decreasing the prevalence of deafness in the future.

Child, Preschool ; Connexin 26 ; Connexins ; genetics ; DNA, Mitochondrial ; genetics ; Female ; Genetic Testing ; Hearing Loss ; diagnosis ; etiology ; genetics ; Hearing Tests ; Humans ; Infant ; Male ; Membrane Transport Proteins ; genetics ; RNA, Ribosomal ; genetics

OBJECTIVETo observe the exercise single photon emission computed tomography (SPECT) myocardial perfusion imaging of patients with myocardial bridge and assess the association between myocardial ischemia and extent of myocardial systolic compression.

METHODSSeventeen patients with myocardial bridge diagnosed by coronary angiogram were included and underwent exercise SPECT myocardial perfusion imaging.

RESULTSAbnormal SPECT perfusion imaging was evidenced in 12 out of 17 patients with myocardial bridge (2 out of 6 patients with systolic compression induced stenosis < 50%, 3 out of 4 patients with systolic compression induced stenosis between 50% - 75% and 7 out of 7 patients with the systolic compression induced stenosis between 75% - 100%).

CONCLUSIONExercise stress SPECT myocardial perfusion imaging could detect myocardial ischemia in patients with myocardial bridge and abnormal perfusion is positively related to the extent of systolic compression induced stenosis.

Adult ; Aged ; Coronary Angiography ; Exercise Test ; Female ; Heart ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Myocardial Bridging ; diagnostic imaging ; Myocardium ; Technetium Tc 99m Sestamibi ; Tomography, Emission-Computed, Single-Photon ; methods

OBJECTIVETo investigate the features of HBx protein distributed in liver cells and its expression in E. coli.

METHODSThe expression vectors encoding the full length HBx and its mutants were constructed by the routine molecular cloning method. HBx protein expression was detected using Western blotting. The distribution feature of HBx protein in liver cells was examined using the fluorescence confocal microscopy. A series of purified HBx fusion proteins were obtained by glutathione-sepharose 4B affinity chromatography.

RESULTSThe expression vectors were successfully constructed for the full length HBx and its mutants. HBx was found distributed uniformly in the nuclei but granularly in the cytoplasm of the liver cells. Under optimal conditions, the mutant GST-HBx (72-120aa) was easily degraded.

CONCLUSIONThis study may provide a basis for further study on the biological function of HBx at the protein level.

Carcinoma, Hepatocellular ; pathology ; Cell Line ; Cloning, Molecular ; Escherichia coli ; metabolism ; Genetic Vectors ; Glutathione Transferase ; biosynthesis ; genetics ; Hepatocytes ; cytology ; metabolism ; Humans ; Liver ; cytology ; Liver Neoplasms ; pathology ; Mutation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Trans-Activators ; biosynthesis ; genetics ; Tumor Cells, Cultured

OBJECTIVETo explore the inhibitory effect of combined administration of bear bile powder (BBP) and cyclophosphamide (Cytoxan, CTX) on colorectal cancer liver metastasis by regulating tumor promotion inflammation microenvironment.

METHODThe CRC liver metastasis mode in mice was established through in situ spleenic injection of SL4 tumor cells into spleens. The mice were randomly divided into 5 groups: the model group, the CTX (80 mg x kg(-1)) treatment group, the CTX + BBP high dose (300 mg x kg(-1)) group, the CTX + BBP middle dose (150 mg x kg(-1)) group and the CTX + BBP low dose (75 mg x kg(-1)) group. Mice were orally administered with drugs for 12 days, and sacrificed on the 13'h day for weighing their spleens and lives, HE staining, and immunofluorescence analysis. Their peripheral blood, and metastatic tumor in spleens and lives were analyzed with flow cytometry.

RESULTSpleen and liver weights of the: CTX treatment group and other doses groups were significantly lower than that of the model group. HE staining and immunofluorescence analysis showed that lymphocyte infiltration was detected in normal tissues, and macrophages infiltration was observed around the tumor tissues. Flow cytometry analysis showed that the number of T-lymphocytes in peripheral blood of different doses groups were much higher than that of the CTX treatment group (P < 0.05), with the rise in the ratio of CD4/CD8; the total number of lymphocytes in spleen cell suspension increased in different doses groups, compared to the CTX treatment group, with notable increase in B cells (P < 0.05) and significant decrease in CD11b, F4/80 cells (P < 0.05). The combined treatment showed less monocyte macrophages in liver metastasis than that of the CTX treatment group.

CONCLUSIONThe combined treatment of bear bile powder and cyclophosphamide has the effect in not only protecting liver and increase immunity, but also in anti-inflammation and antitumor by regulating tumor microenvironment and reducing the collection of mononuclear macrophages. Particularly, the combined administration of low dose of bear bile powder and CTX shows the most significant effect in reducing inflammatory cell infiltration.

Animals ; Bile ; chemistry ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Combined Modality Therapy ; Cyclophosphamide ; administration & dosage ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; physiopathology ; secondary ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Microenvironment ; drug effects ; Ursidae

According to the professional characteristics of the operating room,on the basis of basic principles of hierarchical management and post management of nursing department,taking clinical needs as guiding ideology,combined with the development needs of surgical departments,we developed the operating room nursing staff management model,and set up 23 jobs.We adjusted it accordingly in practice,and constantly optimized nurses' career plan by providing clinical,teaching,research,management and other multi-channel development direction,meanwhile provided better quality care for patients.

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.