Objective To observe the effects of tetrandrine on the proliferation,migration,and invasion of melanoma cell B16,and to explore its effects on epithelial mesenchymal transition(EMT)and potential regulatory mechanisms.Methods(1)The proliferation of B16 cells was detected by CCK-8 assay after 0,2,4,6,8 and 10 μmol·L-1 of tetrandrine intervention for 24 and 48 hours.The colony formation ability of B16 cells was detected by plate clone formation assay after 1,2 and 4 μmol·L-1 of tetrandrine intervention;the migration and invasion ability of B16 cells was detected by cell scratch assay and Transwell invasion assay;the expressions of N-cadherin,Vimentin and E-cadherin related to EMT in B16 cells were detected by Western Blot assay.The mouse melanoma lung metastasis model was replicated by tail vein injection of B16 cells to observe the effects of tetrandrine(50 and 100 mg·kg-1)administered by gavage on the number of metastatic tumor nodules in the lungs of mice.(2)The CTD,SwissTargetPrediction and Similarity Ensemble Approach databases were used to predict the targets of tetrandrine;the GeneCards database was used to search for targets related to melanoma disease;the intersection of these two databases was taken as the potential target of tetrandrine for melanoma treatment.The intersected targets were imported into STRING database to construct protein-protein interaction(PPI)network and screen the core targets;the intersected targets were imported into DAVID database for GO function and KEGG pathway enrichment analysis;and molecular docking between tetrandrine and the core targets was verified by Autodock software.(3)In vivo experimental validation:after intervention of 1,2 and 4 μmol·L-1 tetrandrine,Western Blot method was used to detect the expression of the key pathway AKT/NF-κB/CREB pathway-related proteins;and AKT agonist SC79 was used to validate the replication experiments.Results(1)The IC50 of B16 cells intervened by tetrandrine was 4.273 and 4.085 μmol·L-1 at 24 and 48 hours.Compared with the control group,the colony forming ability,scratch healing rate and invasion rate of cells in the 1,2 and 4 μmol·L-1 tetrandrine group were all significantly reduced(P＜0.05,P＜0.01,P＜0.001);the expressions of cellular Vimentin and N-cadherin protein expressions were significantly down-regulated(P＜0.01,P＜0.001),and E-cadherin protein expression was significantly up-regulated(P＜0.01,P＜0.001).Compared with the model control group,the number of melanoma lung metastatic nodules was significantly reduced in the mice in the high-dose group of tetrandrine(P＜0.05).(2)A total of 60 potential targets were obtained for the treatment of melanoma with tetrandrine;core targets such as AKT1,TNF,CCND1,RELA,CASP9,CHUK,and CREBBP were further screened,among which AKT1 was the most strongly interacting target;the signaling pathways such as apoptosis,FoxO,TNF,PI3K-AKT,and NF-κB were mainly involved.The molecular docking showed that tetrandrine had strong binding activity with AKT1,TNF,RELA and other core targets.Compared with the control group,protein expressions of p-AKT/AKT,p-NF-κB p65/NF-κ B p65,and p-CREB/CREB were significantly down-regulated in the cells of the tetrandrine 1,2,and 4 μmol·L-1 groups(P＜0.05,P＜0.01);protein expressions of p-AKT and p-NF-κB p65 were significantly up-regulated in the cells of the SC79 group(P＜0.001).Compared with the SC79 group,protein expressions of p-AKT,p-NF-κB p65,and p-CREB were significantly down-regulated in the cells of the 2 μmol·L-1 tetrandrine+ SC79 group(P＜0.001).Conclusion Tetrandrine may inhibit the proliferation,migration,invasion and EMT of mouse melanoma by regulating the AKT/NF-κB/CREB pathway,and thus inhibit the lung metastasis of mouse melanoma.

Recent insights collectively suggest the important roles of lysyl oxidase (LysOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms remain elusive. Herein, we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons. Mechanistically, LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) signaling. In addition, overexpression of LysOX via adeno-associated viral vector (AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage. Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile (BAPN) significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage, while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers. These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage. Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.

Bone graft materials have mixed effects of bone repair in the field of oral maxillofacial surgery. The qualitative analyses performed by previous studies imply that autogenous odontogenic materials and autogenous bone have similar effects on bone repair in clinical jaw bone transplantation. This retrospective systematic assessment and network metaanalysis aimed to analyze the best effect of clinical application of autogenous odontogenic materials and autogenous, allogeneic, and xenogeneic bone grafts in bone defect repair. A systematic review was performed by searching the PubMed, Cochrane Library, and other journal databases using selected keywords and Medical Subject Headings search terms. 10 Papers (n = 466) that met the inclusion criteria were selected. The assessment of heterogeneity did not reveal any overall statistical difference or heterogeneity (P = 0.051 [ 0.05), whereas the comparison between autogenous and allogeneic bone grafts revealed local heterogeneity (P = 0.071 0.1). Risk of bias revealed nine unclear studies and one high-risk study. The overall consistency was good (P = 0.065 [ 0.05), and the local inconsistency test did not reveal any inconsistency. The publication bias was good. The confidence regarding the ranking of bone graft materials after GRADE classification was moderate. The effects on bone repair in the descending order were as follows: autogenous odontogenic materials, xenogeneic bone, autogenous bone, and allogeneic bone. This result indicates that the autogenous odontogenic materials displayed stronger effects on bone repair compared to other bone graft materials. Autogenous odontogenic materials have broad development prospects in oral maxillofacial surgery.

【Objective】 To analyze the metagenomics and microbiology of voluntary blood donors in China, so as to assess the potential threats of emerging infectious diseases to the safety of blood transfusion. 【Methods】 12 300 plasma samples (10 mL each) collected by central blood stations in Chongqing, Liuzhou, Urumqi, Mianyang, Wuhan, Nanjing, Mudanjiang, and Dehong Prefecture area from 2012 to 2018 were subjected to total DNA extraction after ultracentrifugation (32 000 rpm/min, centrifugal radius 91.9 mm) in minipools of 160 donations. The metagenomic library was constructed, and deep sequencing was conducted by Illumina Hiseq 4 500. By comparing with reference sequences of bacteria, fungi, parasites and viruses, metagenomic data were analyzed, classification of microbes were identified, and potentially harmful pathogens were evaluated. 【Results】 A total of 632 GB clean data were obtained by deep sequencing, and the top three pathogens were Pseudomonas(0.561 1%), Burkholderia(0.468 7%) and Serratia(4.242 0%). Pathogens with potential threat which could be transmitted by blood transfusion or blood products were found, such as human parvovirus B19(0.126 6%), Leishmania spp(1.348 5%) and Toxoplasma gondii(0.615 8%). 【Conclusion】 Our study analyzed metagenomics of voluntary blood donors in parts of China and revealed pathogens that may cause potential harm to blood safety, which were helpful for targeted prevention and control of emerging infectious diseases.

Objective:To investigate the demand and practical utility of simulation operations specialists (SOS) in simulation teaching modules during the standardized residency training.Methods:Based on the feedback for stimulated courses of standardized residency training, subjective evaluation of all residents, teachers and SOS who participated in simulation courses in 2017-2018 academic year were investigated and studied via the mobile phone online investigation. At the same time, the design data of teaching concept map of relevant curriculum were also included. The SPSS 13.0 was used to conduct the t test and chi-square test. Results:At present, only 26.3% of the preset functions were used in the medical simulation courses based on high-tech medical simulator. Tutors commanded less than 30% functions, while SOS participated in the whole process of the course preparation and commanded 63.6% of the course operations, which was higher than the requirement of teaching concept map (45.5%). Among them, ECG monitoring regulation, venous management and special effects makeup were in greatest needs and were items with the biggest gap between ideality and reality. Resident physicians required SOS to replace the tutors to operate teaching facilities, so as to reduce interruption (37.0%), implications (31.3%) during courses, and improvement of experience sense during the course (32.3%). Furthermore, specialists with clinical background needed more assistance from SOS than those without clinical background ( tQ3=3.204, tQ4=2.573, tQ5=2.660; P<0.05). Differences were found between the actual work content of SOS and their job requirement ( χ2=12.632, P<0.01). Conclusion:SOS plays a significant role in the simulation course of standardized residency training, especially in the course of clinical professional physicians. Auxiliary functions of simulated courses, such as teaching aids management, special effects makeup, course designing, qualified SP and others are the main necessities for SOS at present. Participation of tutors and SOS together is essential to ensure a good development and performance of medical simulation courses for standardized residency training.

Objective:To explore the risk factors for diarrhea in Intensive Care Unit (ICU) patients with enteral nutrition support by Meta-analysis, so as to provide a basis for the prevention of diarrhea.Methods:Literature on risk factors for diarrhea in ICU patients with enteral nutrition were searched in PubMed, Web of Science, Embase, the Cochrane of Library, China National Knowledge Infrastructure, Wanfang Data and SinoMed by computer from the database building to June 30, 2020. RevMan 5.1 was used for analysis.Results:A total of 14 literatures were included with 16 related risk factors. After Meta-analysis, statistically significant risk factors included hypoproteinemia ( OR=2.51) , age ( OR=2.08) , fasting before enteral nutrition ( OR=4.70) , mechanical ventilation ( OR=2.24) , use time of enteral nutrition preparation ( OR=1.35) , dosage of enteral nutrition preparation ( OR=1.01) , speed of enteral nutrition preparation ( OR=1.03) , potassium tube feeding ( OR=1.65) , antibiotic ( OR=1.98) , gastric motility drugs ( OR=2.06) and acid inhibitor ( OR=2.62) . Conclusions:The risk factors for diarrhea in ICU patients with enteral nutrition support include patient's own and disease factors (hypoproteinemia, age, fasting before enteral nutrition, mechanical ventilation and APACHE Ⅱ) , nutrition preparation factors (use time, dosage and speed of enteral nutrition preparation) as well as drug factors (potassium, antibiotic, gastric motility drugs and acid inhibitor) . Given that there are many risk factors for diarrhea in ICU patients with enteral nutrition support, clinically targeted preventive measures should be taken to reduce the risk of its occurrence.

Objective To explore the relationship among nurses′perceptions of patient safety culture, nursing practice environment and the report barrier of nursing adverse event. Methods Totally 513 registered nurses from six hospitals in Zhengzhou were investigated with Patient Safety Culture Assessing Scale, Work Environment Questionnaire and Report Barriers Questionnaire. Results The mean scores of nurses′perceptions of patient safety culture, nursing practice environment and report barriers of nursing adverse events were (3.85±0.55), (3.84±0.53) and (2.47±0.55). The nurses′perceptions of patient safety culture were positively correlated to nursing practice environment (r=0.393,P<0.01), negatively correlated to report barriers of nursing adverse events (r=-0.372,P<0.01). The influencing factors of nurses′perceptions of patient safety culture were colleague relationship, punitive culture, allocation of medical resources, marital status, quality control, significance of report, gender and education, which could explain 33.8 percent for the variances. Conclusions The level of nurses′perceptions of patient safety culture is higher than the average level. The nursing managers should build supportive nursing practice environment and the non-punitive reporting system of nursing adverse events. Cultivate the beliefs and attitudes of nursing safety and focus on the impact of occupational stress to patient safety in order to enhance safety nursing.

The magnetic Illite ( MILT) was firstly prepared by an effective polyol-medium solvothermal method. Based on these 3-( methacryloyloxy) propyl trimethoxysilane ( MILT-MPS), magnetic molecularly imprinted polymers (MMIPs) were further synthesized via atom transfer radical polymerization in a mixture solution of methanol and deionized water. The as-prepared MMIIPs were characterized by FT-IR, TEM), XRD, TGA and vibrating sample magnetometer (VSM), and the results indicated that the MMIIPs exhibited magnetic sensitivity ( Ms =3. 866 emu / g ), thermal stability and a larger specific surface area (109. 58 m2 / g). The batch mode adsorption studies were carried out to investigate the recognition specificity and selective capacity. The Langmuir isotherm model was fitted to the equilibrium data, and the monolayer adsorption capacity of MMIPs at 25℃ was 86. 58 mg / g. The selective recognition experiments demonstrated high affinity and selectivity of MMIPs towards ciprofloxacin ( CIP) over competitive compounds. Combined with high performance liquid chromatographic analysis technology, the prepared MMIIPs were successfully applied to extract and enrich trace CIP in environmental samples with the CIP recoveries from 93. 4% to 98. 3% and the limit of detection of 0. 01 mg / L.

Objective To investigate the virological response in hepatitis C virus (HCV)genotype 1b relapsers after 48 weeks of peginterferon/ribavirin (peg-IFN/RBV)combination retreatment,and to explore the predictive value of interleukin (IL )-28B rs12978960 genetic polymorphismon virological response.Methods From 2012 to 2014,genotype 1b chronic hepatitis C (CHC)relapsers in He′nan Provincial People′s Hospital were retreated with combined peg-IFN/RBV for 48 weeks and followed up for 24 weeks off-treatment.Host IL-28B genetic polymorphism was detected.Predictive factors associated with virological response and sustained virological response (SVR)were analyzed.Independent-samples t test was conducted in continuous variables,whileχ2 test or Fisher exact probability test was conducted in counts data.Results A total of 61 patients finished 48 weeks of peg-IFN/RBV combination therapy and were further followed up for 24 weeks off-treatment.Mean age was (46.7 ±12.4)years.Thirty-seven patients (60.7%)were male and 49 were rs12978960 CC genotype.After 48 weeks of retreatment with peg-IFN/RBV and 24 weeks of off-treatment follow-up,40 patients (65 .6%)achieved SVR.Rapid virological response (RVR)and SVR of younger patients were both significantly higher than those of older patients (100.0% vs 67.4% and 85 .0% vs 47.6%,respectively;both P =0.006).IL-28B rs12978960 genotype was predictive to RVR and SVR.Patients with RVR and SVR had higher carriage rates of IL-28B rs12978960 CC genotype compared with those without RVR and SVR (both P <0.05 ).Patients with CC genotype had higher rates of RVR (34.1 % vs 0;χ2 = 10.625 ,P =0.006 ),end-of-treatment virological response (84.1 % vs 70.6%;χ2 =5 .563,P =0.039 )and SVR (77.3% vs 35 .3%;χ2 =9.572,P =0.007)than those with CT/TT genotype.However,there were no statistical differences of extended RVR (34.1 % vs 29.4%;χ2 =0.122,P =0.809)and early virological response (79.5 % vs 82.3%;χ2 =0.612,P =0.964).Conclusions Retreatment with antiviral therapy is necessary in CHC patients with genotype 1b. IL-28B rs12978960 genetic polymorphism is predictive to the SVR of retreatment,especially for patients without RVR,which will provide individualized treatment and optimize the treatment strategy.

Objective To study the effect of network peer education on the 131I treatment adherence in patients with thyroid cancer.Methods A total of 120 patients with thyroid cancer who performing 131 I treatment from April 2012 to April 2014.They were divided into intervention group 61 cases and control group 59 cases according to the hospital ward number.Control group was given routine health education and intervention group was given network peer education.The data from the habits,drug therapy,grasp the situation,the equivalent monitoring of the relevant knowledge of 4 different dimensions of treatment adherence for patients were investigated and compared before discharge by using questionnaire and examination method.Results The incidence of the good habits,drug therapy,grasp the situation,and the equivalent monitoring reaching the standard were 96.7％(59/61),98.4％(60/61),96.7％(59/61),100.0％(61/61) in intervention group,and 54.2％(32/59),76.3％(45/59),79.7％(47/59),89.8％(53/59) in control group,there were significant differences,x2=29.54,13.38,8.47,4.56,P＜0.01 or ＜0.05.Conclusion Network peer education for patients with thyroid cancer during the 131I treatment can effectively improve the patient's treatment adherence,has positive significance for the treatment.