Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

Object To study the efficacy and potential mechanism of Tongbianling capsule in constipation. Methods The effects of Tongbianling capsule on intestinal motility in normal mice and carbon powder propulsion rate in small intestine of constipation model mice after were observed administration. The potential targets and key pathways of Tongbianling capsule in treating constipation were identified through network pharmacology. To verify the mechanism, the expression of p-PI3K/PI3K, p-AKT/AKT and CASP3 proteins in mouse colon tissue was detected by the western blot. Results The time for mice to excrete the first black stool was shortened and the number of fecal particles was increased in Tongbianling capsule administration group, and the carbon powder propulsion rate of mice in each Tongbianling capsule administration group was increased. The results of network pharmacology showed that treatment of constipation by Tongbianling capsule may be related to signaling pathways such as PI3K-Akt signaling pathway and 5-HT. The protein expression of p-PI3K/PI3K, p-AKT/AKT, and CASP3 in mouse colon tissue could be significantly downregulated in administration group. Conclusion Tongbianling capsule could effectively promote intestinal peristalsis in mice, increase the frequency of defecation, and effectively treat constipation. The mechanism of its action may be related to the direct or indirect regulation of intestinal motility by the PI3K-Akt signaling pathway.

Objective To establish the fingerprint of Jianggui granules, and evaluate it by chemometrics. Methods The fingerprint of Jianggui granules was established by HPLC. Similarity evaluation system of chromatographic fingerprint of TCM （2012 edition） was used to evaluate the similarity evaluation. Then, the quality of the drug was assessed by cluster analysis （CA）, principal components analysis （PCA） and partial least squares discriminant analysis （PLS-DA）. Results The characteristic fingerprint of Jianggui granules was established and 18 common peaks were verified. Five chromatographic peaks were identified，i.e. Puerarin, glycyrrhizin, cinnamic acid, cinnamaldehyde and ammonium glycyrrhizinate. The similarities of samples were >0.9. Results of CA showed that 14 batches of samples could be classified into two categories：S1 and S4 were grouped into one category；others were grouped into the other category. The results of PCA showed that the cumulative contribution rate of the first two principal components was 96.61%. The results of OPLS-DA showed that the eleven peaks with VIP value >1 were puerarin （peak 8）, glycyrrhizin （peak 14）, cinnamaldehyde （peak 17） and ammonium glycyrrhizinate （peak 18）. Conclusion HPLC fingerprint of Jianggui granules was established. The established method was accurate and reliable，which could be used in quality evaluation of Jianggui granules.

Lipoprotein-associated phospholipase A2(Lp-PLA2)is a protein composed of 441 amino acids,which can promote the aggregation of inflammatory cells to the inflammatory response site and the release of inflammatory factors.It can promote the synthesis of matrix metalloproteinases,increase the number of foam cells and extra cel-lular matrix in atherosclerotic plaque,attenuate plaque fiber cap and prone to rupture,thus promote the onset of acute coronary syndrome(ACS).Therefore,the determination and regulation of Lp-PLA2 levels in patients with ACS are clinically significant.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

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.

Humans ; Cytomegalovirus ; Cytomegalovirus Infections ; Antigens, Viral ; Immunity ; Autoimmune Diseases ; CD8-Positive T-Lymphocytes

Objective To systematically evaluate the risk factors associated with the occurrence of nosocomial infections(NI)in patients undergoing extracorporeal membrane oxygenation(ECMO)support.Methods A computerized systematic search was performed aross the Chinese databases including CNKI,Wanfang Database,China Biomedical Literature Database(CBMdisc),and Weipu,as well as the English databases such as PubMed,EMBase,Web of Science,and the Cochrane Library for case-control or cohort studies on the risk factors of hospital-acquired infections in patients undergoing ECMO support from the time of database construction to February 2023.The relevant literatures were screened by two researchers independently.Meta-analysis was performed using RevMan 5.4 software.Results A total of 20 papers,including 2 746 patients and 16 risk factors,were included.Meta-analysis results showed that older age[>50 years:odds ratio(OR)= 2.87,95％ confidence interval(95％ CI)was 1.24-6.63,P = 0.01;>65 years:OR = 1.66,95％ CI was 1.22-2.26,P = 0.001],combined hypertension(OR = 1.48,95％ CI was 1.01-2.15,P = 0.04),combined diabetes mellitus(OR = 1.40,95％ CI was 1.02-1.94,P = 0.04),sequential organ failure assessment(SOFA)was higher(OR = 1.06,95％ CI was 1.02-1.10,P = 0.000 7),the installation of ECMO in the intensive care unit(ICU,OR=1.48,95％ Ciwas 1.11-1.99,P=0.008),ECMO course(OR=1.27,95％ Ciwas 1.05-1.54,P = 0.01),ventilator-assistance for >48 hours(OR = 4.91,95％ CI was 2.40-10.05,P<0.000 1),and tracheotomy(OR = 9.56,95％ CI was 3.60-25.35,P<0.000 01)were identified as ECMO risk factors for hospital-acquired infections in patients.Conclusion Older age,combined hypertension,diabetes mellitus,higher SOFA,ECMO installation site in ICU,ECMO course,ventilator assistance>48 hours,tracheotomy are the risk factors for the occurrence of hospital-acquired infections in patients with ECMO,healthcare professionals should promptly identify the risk factors related to hospital-acquired infections,and take active and effective measures against controllable risk factors,including early intervention to prevent the occurrence of NI in ECMO patients.

Objective:To develop a questionnaire for voluntary care of the disabled elderly based on the theory of planned behavior, and test its reliability and validity.Methods:With the theory of planned behavior as the theoretical framework, a questionnaire entry pool was formed on the basis of extensive reading of domestic and foreign literatures and semi-structured interviews, and the questionnaire items were screened by Delphi method. From July to August 2020, 350 nursing staff from 10 hospitals in Suzhou were selected by convenience sampling method, and the reliability and validity of the questionnaire were tested, and the formal questionnaire was finally formed.Results:Totally 350 questionnaires were distributed in this study, and 330 copies of effective questionnaires were recovered, with an effective recovery rate of 94.29%. This questionnaire included a total of 26 items in 4 dimensions, including attitude, subjective norms, perceived behavioral control and behavioral intention. Cronbach′s α coefficient was 0.977, split-half reliability was 0.906, test-retest reliability was 0.84, the content validity index (CVI) of total questionnaire was 0.97, item-level CVI value was 0.88 to 1.00. Four exploratory factors were extracted, and cumulative contribution rate was 80.03%.Conclusions:The questionnaire has good reliability and validity, which can well explain and predict the willingness of nursing staff to volunteer for the disabled elderly, and can also provide incentive basis for policy makers and managers.

Two-dimensional code technology is widely used in daily life,and its application is relatively rare in medical education.Students organized write the Chinese and English slices' information by the way of extracurricular teaching activities,and two-dimensional code transformed from slices' information as label was pasted onto slice to made slice specimen with two-dimensional code.The students can quickly and accurately read the slice information by scanning the two-dimensional code.This practice can stimulate students' interest in learning and creative ability.It not only creates convenient conditions for the opening of the histology experiment and the independent study of the students,but also provides a way of thinking for the information management of the experimental teaching.