Objective:To investigate the application effect of problem-based learning (PBL) combined with scenario simulation in nursing teaching of needlestick injuries.Methods:A total of 123 undergraduates majoring in nursing were selected as research subjects from the classes of 2020 and 2021 in a medical university. The 60 undergraduates in the class of 2020 were established as control group and were given PBL teaching, and the 63 undergraduates in the class of 2021 were established as experimental group and were given PBL combined with scenario simulation. The two groups were compared in terms of theoretical score, skill examination score, and knowledge-attitude-practice (KAP) score of needlestick injury knowledge. SPSS 25.0 was used to perform the t-test, the chi-square test, and the rank sum test. Results:Compared with the control group, the experimental group had significantly higher scores of theoretical examination [(84.43±5.03) vs. (80.30±4.81), P<0.001] and skill examination [(88.40±4.26) vs. (83.55±5.84), P<0.001], as well as significantly higher scores of knowledge [(14.46±1.03) vs. (13.18±1.23), P<0.001], attitude [(52.59±3.09) vs. (48.05±3.06), P<0.001], and practice [(67.37±4.28) vs. (62.17±3.92), P<0.001] in KAP questionnaire. Conclusions:PBL combined with scenario simulation teaching can effectively improve the knowledge of protection against needlestick injuries and related skills in nursing students, enhance their awareness of needlestick injuries, and promote the protective behavior against needlestick injuries.

Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.

Objective To comprehensively characterize the diterpene alkaloids in Radix Aconiti Kusnezoffii.Methods The diterpene alkaloids were isolated and purified by strong acid cation exchange resin solid phase extraction column(SCX-SPE),and identified by ultra high performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS).Results A total of 99 diterpene alkaloids were identified from Radix Aconiti Kusnezoffii,including 27 diester diterpene alkaloids(DDA),29 monoester diterpene alkaloids(MDA),40 amide diterpene alkaloids(ADA),2 polyester diterpene alkaloids(PDA)and 1 long-chain ester diterpene alkaloid(LDA).Conclusion The SCX-SPE combined with UHPLC-Q-Exactive Orbitrap MS method,established in this paper,can rapidly identify a large number of diterpene alkaloids in Radix Aconiti Kusnezoffii,which provides scientific proof for the study of pharmacodynamic substance basis and quality control of Radix Aconiti Kusnezoffii.

Objective To investigate the medical expense control model of rational drug use based on the China healthcare security diagnosis related groups(CHS-DRG)simulation in Beijing in 2021.Methods By analyzing the simulated operation data from January to March 2021 before the intervention,the groups with rational drug management improving potential among the top three surgical disease groups in terms of the number of cases enrolled in the surgical department were selected.Then,the targeted intervention and guidance were implemented to the selected disease groups.Finally,the analysis was obtained by comparing the changes in several key indicators such as the average drug cost,average antibacterial drug cost,average surplus and average length of stay during June to August 2021.Moreover,the differences in antimicrobial drug use intensity and hospital infection reporting of the department as a whole where the problematic groups were located were also investigated.Results Before the intervention,the otolaryngology related groups(including DD29 and DE19),urology surgery related groups(including LD19 and LJ13)could be improved in antibacterial drug use during the perioperative period.Meanwhile,the chest surgery related group(including EB19)had space to be improved in auxiliary medication.After the intervention,the five groups'average drug cost and average antibacterial drug cost in the otolaryngology and urology surgery departments are all decreased.The antibiotics use intensity is also declined in otolaryngology and urology surgery departments.The average surplus of otolaryngology and urology surgery related groups are increased,with the DE19 disease group in ENT also achieving a profit turnaround.As for the indicators related to the quality of care,there were no significant differences in the groups'average length of stay and nosocomial infection reporting of these departments.Conclusion The hospital operation based on CHS-DRG payment is both an opportunity and a challenge.The all-inclusive payment model has prompted hospitals to take the initiative in controlling costs,and the exploration of a rational medication management and cost-control model related to disease groups has begun to show results in terms of cost reductions without affecting the quality of medical care.The research can also provide a solid foundation for the CHS-DRG actual payment and sustainable development of medical insurance fund.

Bacillus cereus belongs to Gram-positive bacteria, which is widely distributed in nature and shows certain pathogenicity. Different B. cereus strains carry different subsets of virulence factors, which directly determine the difference in their pathogenicity. It is therefore important to study the distribution of virulence factors and the biological activity of specific toxins for precise prevention and control of B. cereus infection. In this study, the hemolysin BL triayl was expressed, purified, and characterized. The results showed that the bovine pathogenic B. cereus hemolysin BL could be expressed and purified in the prokaryotic expression system, and the bovine pathogenic B. cereus hemolysin BL showed hemolysis, cytotoxicity, good immunogenicity and certain immune protection in mice. In this study, the recombinant expression of hemolysin BL triayl was achieved, and the biological activity of hemolysin BL of bovine pathogenic ceroid spore was investigated. This study may facilitate further investigating the pathogenic mechanism of B. cereus hemolysin BL and developing a detection method for bovine pathogenic B. cereus disease.
Cattle ; Animals ; Mice ; Bacterial Proteins/metabolism* ; Bacillus cereus/metabolism* ; Hemolysin Proteins/metabolism* ; Virulence Factors/metabolism* ; Enterotoxins/metabolism*

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

OBJECTIVE To analyze and identify the metabolites of isoimperatorin in normal rats in vivo. METHODS After the rats were intragastrically administered, the plasma, urine and feces samples of rats in normal and dosed groups were collected, and the samples were processed by solid phase extraction. Then, UHPLC-HRMS(Q-Exactive Orbitrap MS) high- resolution mass spectrometry was used to analyze biological samples, and the metabolites were screened and identified. RESULTS In both positive and negative ion modes, a total of 32 metabolites were accurately analyzed and identified based on the precise molecular masses obtained, chromatographic retention behavior, control mass spectral cleavage patterns, characteristic fragment ions, and relevant literature reports. The main metabolic pathways were furan ring opening, lactone hydrolysis, oxidation, methylation, glucuronidation, sulfation and their complex reactions. Among them, the glucuronidation product was discovered for the first time. CONCLUSION This study comprehensively clarifies the transformation pathways of isoimperatorin in rats, which can provide a basis for its pharmacodynamic study and metabolism study analysis of the other furocoumarins.

Objective:Based on the application and funding status of National Natural Science Foundation of China (NSFC) in the field of oral and craniofacial sciences (H15), we analyzed the current status of basic research of the Oral and Craniofacial Sciences (OCS) in China, and provided the references for the sustainable and efficient funding of basic research and scientific frontier exploration in the field, supporting the construction of talents and teams, and enhancing the development of OCS in China.Methods:The data of both applied and funded grants of H15 in NSFC from 2010 to 2021 were analyzed, including the number of applications and funding, the amount of funding, the funding rate, the research direction and the supporting units. The status of basic research of H15 was summarized.Results:From 2010 to 2021, H15 received 15 060 applications and funded 2 569 grants. The overall funding rate of H15 was 17.06%, and the total funding amount was 1 140.305 million yuan. The applications and funded projects of H15 were mainly focused on the General Projects and Youth Science Fund Projects, accounting for 90.33% (13 604/15 060) and 88.71% (2 279/2 569) of the total number of applications and funded projects, and 78.05% (89 002.5/114 030.5) of the total funding amount. In terms of talent training, the National Science Foundation for Distinguished Young Scholars received 65 applications, and 6 were founded, with a funding rate of 9.23%. The National Science Foundation for Outstanding Young Scholars received 85 applications, and 13 were founded, with a funding rate of 15.29%. In recent years, the number of applications has gradually increased and the number of grants has remained relatively stable. Among the nine sub-categories of H15, the top three in terms of the number of applications and grants were H1502, H1504, and H1507. H1502 (repair and regeneration of oral and craniofacial tissue and organ defects) received 2 760 applications, and 510 were funded. H1504 (periodontal and oral mucosal diseases) received 2 475 applications, and 419 were funded. H1507 (restoration of tooth defects and loss, and correction of dental deformities) received 2 270 applications, and 367 were funded. Peking University and Sichuan University ranked first and second with 1 092 and 1 001 applications, respectively. The top five recipients were Sichuan University (327 items), Peking University (260 items), Wuhan University (204 items), Shanghai Jiao Tong University (198 items) and the Fourth Military Medical University of the People's Liberation Army (193 items). The funding rates were 32.67%, 23.81%, 23.02%, 21.69% and 29.11%, respectively.Conclusions:Under the support of NSFC, the basic research of oral and craniofacial sciences has been developed in an all-round way. In recent years, the talent training of all echelons has increased year by year, the research direction and geographical coverage is comprehensive, and project support organization has its own research focus and discipline advantages, making contributions to the realization of the goal of healthy China and the progress of world medicine.

BACKGROUND: Fibroblast activation protein (FAP) is one of the surface markers of cancer-associated fibroblasts (CAFs) and is closely related to the malignant characterization of CAFs. SP13786 is a specific micromolecule inhibitor of FAP and this study is to investigate the effects and mechanism of SP13786 on the migration and invasion of A549 cells through regulating exosomes of CAFs. METHODS: CAFs and paracancerous fibroblasts (PTFs) were isolated and subcultured from freshly resected lung adenocarcinoma tissues and paracancerous normal tissues separately. MTT assay was used to detect the proliferation of CAFs incubated by different concentrations of SP13786; PTFs-exo, CAFs-exo and CAFs+SP13786-exo were extracted by polymer precipitation method. The A549 cells were divided into Ctrl group, PTFs group, CAFs group and SP13786 group and each group was incubated with DMEM, PTFs-exo, CAFs-exo and CAFs+SP13786-exo separately. Laser confocal microscope was used to observe the endocytoses of exosomes by A549 cells. The expression of alpha-smooth muscle actin (α-SMA) and FAP in PTFs and CAFs and the expression of E-cadherin, N-cadherin, Slug, Stat3 and P-Stat3 in A549 cells were detected by immunofluorescence, immunohistochemistry and Western blot. The migration and invasion ability of A549 cells were detected by cell scratch and transwell methods. RESULTS: α-SMA and FAP were expressed much higher in CAFs than that in PTFs which indicate that CAFs and PTFs were successfully obtained from lung adenocarcinoma and paracancerous tissues (P<0.05). MTT showed that the 50% inhibitory concentration (IC50) of SP13786 for CAFs was about 3.3 nmol/L. In addition, SP13786 can significantly decrease the expression of α-SMA and FAP in CAFs which means that targeted inhibition of FAP could reduce the malignant characteristics of CAFs (P<0.05). Laser confocal microscope found that exosomes from CAFs could be taken up by A549 cells and scratch and transwell tests showed that the endocytosed CAFs-exo could promote the migration and invasion of A549 cells (P<0.001), while FAP inhibitor SP13786 could inhibit the effects of CAFs-exo on A549 cells (P<0.05). Furthermore, Immunofluorescence and Western blot showed that CAFs-exo could promote EMT by decreasing E-cadherin expression and increasing N-cadherin, Slug expression in A549 cells while FAP inhibitor SP13786 could significantly supress CAFs-exo-induced epithelial-mesenchymal transition (EMT) of A549 cells (P<0.05). Moreover, the expression of P-Stat3 was obviously increased in A549 cells of CAFs group and significantly down-regulated in SP13786 group (P<0.05) whereas there was no significant difference in total Stat3 between CAFs and SP13786 groups (P>0.05). Finally, WP1066 (a specific inhibitor of Stat3) was used to comfirm whether SP13786 could influence EMT of A549 cells by inhibiting Stat3 phosphorylation via CAFs-Exo. The results showed that when the phosphorylation of Stat3 in CAFs group was inhibited by WP1066, SP13786 could not influence the P-Stat3 expression and EMT of A549 cells anymore (P>0.05). CONCLUSIONS As a specific micromolecule inhibitor of FAP, SP13786 indirectly inhibits the migration and invasion of A549 cells by affecting exosomes of CAFs. The possible mechanism is to inhibit the phosphorylation of Stat3 and thus affect the EMT of A549 cells.

Immune checkpoint inhibitors (ICIs) can cause adverse reactions in the nervous system, with the incidence rate ranging from 0.1% to 12%, and 80% occurring within the first 4 months of ICI application. It can cause lesions in various parts of the nervous system, including aseptic meningitis, meningoencephalitis, necrotizing encephalitis, brainstem encephalitis, transverse myelitis and other central nervous system diseases. It can also cause cranial peripheral neuropathy, multifocal radicular neuropathy, Guillain-Barre syndrome, spinal radicular neuropathy and myasthenia gravis, myopathy, etc. For these complications of the nervous system, diagnosis could be made by sufficient collection of disease manifestations combined with imaging, cerebrospinal fluid examinations, electro-encephalogram or electro myography to exclude infection or tumor progression. In the treatment of severe cases, ICIs should be discontinued and treated with high doses of glucocorticoid or gamma globulin with systemic support. After neurological adverse reactions, the prognosis of severe cases is poor.