Objective:To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia(AML)by network pharmacology,and to clarify the active components and their mechanisms in treating AML.Methods:The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets were predicted by SwissTargetPrediction Database.The AML-related genes and protein targets were retrieved from the SymMap Database,the GeneCards Human Gene Database,the DisGeNET Database,and the Online Mendelian Inheritance in Man(OMIM)Database.The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.The drug-active component-target network and protein-protein interaction(PPI)network were constructed by Cytoscape 3.8.0 software,and the core genes were selected by CytoNCA plugin;the molecular docking was conducted by AutoDock software.Results:After filtering by databases,39 active components were identified,and 148 common targets between dandelion-mulberry leaf and AML were collected.The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways,positive regulation of kinase activity,and oxidative stress responses.The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B(PI3K-AKT)signaling pathway,the tumor necrosis factor(TNF)signaling pathway,and the Janus kinase/signal transducer and activator of transcription(JAK-STAT)signaling pathway.The key targets were identified by topological analysis including signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),recombinant human epidermal growth factor(EGF),vascular endothelial growth factor A(VEGFA),oncogene MYC,tumor protein P53(TP53),mitogen-activated protein kinase 3(MAPK3),cysteiny asparate specific protease-3(CASP3),oncogene SRC,heat shock protein 90 alpha family class A member 1(HSP90AA1),tenascin XB1(CTNNB1),phosphoinositide kinase-3 catalytic subunit alpha(PIK3CA),interleukin 6(IL-6),TNF,mitogen-activated protein kinase 1(MAPK1),and phosphatidylinositide kinase-3 regulatory subunit 1(PIK3R1).The molecular docking results showed the highest affinity pairing to be taraxerol with MYC(-8.74 kcal·mol-1),and quercetin,kaempferol,luteolin,and artemetin demonstrated good binding affinities with various targets.Conclusion:The main active components of dandelion-mulberry leaf,such as quercetin,taraxerol,kaempferol,luteolin,and artemetin,may exert the anti-AML effect by regulating AKT1,STAT3,HSP90AA1,IL-6,and MAPK1;regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.

Objective To investigate the clinical significance of serum S100 calcium binding protein(S100 A4)and S100A12 in patients with severe traumatic brain injury(sTBI).Methods A total of 147 sTBI pa-tients admitted to Handan Central Hospital from March 2021 to March 2023 were selected as the sTBI group,and 50 healthy subjects who underwent physical examination in Handan Central Hospital during the same pe-riod were selected as the control group.The correlation between S100A4,S100A12 levels and brain injury markers and the influencing factors of early death in sTBI patients were analyzed,and the predictive value of serum S100A4 and S100A12 for early death in sTBI patients was studied.Results The serum levels of S100A4,S100A12,myelin basic protein(MBP),S100B and neuron specific enolase(NSE)in sTBI group were significantly higher than those in control group(P＜0.05).The serum levels of S100A4 and S100A12 were positively correlated with MBP,NSE and S100B in sTBI patients(P＜0.05).Multivariate Logistic regression analysis showed that decreased Glasgow coma scale(GCS)score on admission and increased serum levels of S100A4,S100A12,MBP,NSE and S100B were risk factors for early death in sTBI patients(P＜0.05).Receiv-er operating characteristic curve showed that the combination of serum S100A4 and S100A12 with GCS score,MBP,NSE and S100B was superior to any single detection in predicting early death in sTBI patients.Conclu-sion The serum levels of S100A4 and S100A12 are increased in sTBI patients,which are related to the aggra-vations of brain injury and early death.The combined detection of S100A4 and S100A12 has a good predictive value for early death in sTBI patients.

Wound infections, secondary to acute and chronic wounds caused by mechanical, thermal, chemical factors, etc, not only delay wound healing but also may lead to mortality. The prolonged or inappropriate use of antibiotics lead to the growth of drug-resistant bacteria, resulting in refractory wound infections and poor treatment outcomes, which highlights the urgent need for effective therapies. Bacteriophages show great promise in treating drug-resistant wound infections due to their effectiveness in killing drug-resistant bacteria, their good resistance against bacterial biofilm (BBF) and their absence of cytotoxicity to eukaryotic cells. However, the mechanisms underlying bacteriophages′ resistance against BBF remain incompletely understood and their antibacterial efficacy for wound infections may also vary. For this purpose, the authors reviewed the biological characteristics and mechanisms of bacteriophages and their application in antibacterial therapies for wound infections, aiming to provide a reference for further research and application of bacteriophages in the treatment of wound infections.

CRISPR/Cas9 has been widely used in engineering Saccharomyces cerevisiae for gene insertion, replacement and deletion due to its simplicity and high efficiency. The selectable markers of CRISPR/Cas9 systems are particularly useful for genome editing and Cas9-plasmids removing in yeast. In our previous research, GAL80 gene has been deleted by the plasmid pML104-mediated CRISPR/Cas9 system in an engineered yeast, in order to eliminate the requirement of galactose supplementation for induction. The maximum artemisinic acid production by engineered S. cerevisiae 1211-2 (740 mg/L) was comparable to that of the parental strain 1211 without galactose induction. Unfortunately, S. cerevisiae 1211-2 was inefficient in the utilization of the carbon source ethanol in the subsequent 50 L pilot fermentation experiment. The artemisinic acid yield in the engineered S. cerevisiae 1211-2 was only 20%-25% compared with that of S. cerevisiae 1211. The mutation of the selection marker URA3 was supposed to affect the growth and artemisinic acid production. A ura3 mutant was successfully restored by a recombinant plasmid pML104-KanMx4-u along with a 90 bp donor DNA, resulting in S. cerevisiae 1211-3. This mutant could grow normally in a fed-batch fermentor with mixed glucose and ethanol feeding, and the final artemisinic acid yield (> 20 g/L) was comparable to that of the parental strain S. cerevisiae 1211. In this study, an engineered yeast strain producing artemisinic acid without galactose induction was obtained. More importantly, it was the first report showing that the auxotrophic marker URA3 significantly affected artemisinic acid production in a pilot-scale fermentation with ethanol feeding, which provides a reference for the production of other natural products in yeast chassis.
Artemisinins ; Fermentation ; Saccharomyces cerevisiae/metabolism* ; Saccharomyces cerevisiae Proteins/metabolism*

Objective:To investigate the relationship between abdominal visceral adipose tissue (VAT) and cardiometabolic risk (CMR) through quantitative computed tomography (QCT).Methods:The present study included 76226 participants. Abdominal fat areas were measured using the QCT Pro Model 4 system. Cardiometabolic indices were collected, including systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, triglyceride, and low-density and high-density lipoprotein cholesterols CMR score was the sum of abnormal blood pressure, fasting glucose, triglyceride, and high-density lipoprotein cholesterol. Restricted cubic spline and ordered logistic regression models were applied.Results:The mean age was 50±13 years and the percentage of men was 58.8%. The level of VAT area was higher in men than in women (191.7±77.1 cm 2 vs 116.4±56.2 cm 2, P<0.0001 for all). After adjustment for age, the cardiometabolic indices except high-density lipoprotein cholesterol increased with increasing VAT area. When VAT area was 300 cm 2, age-adjusted odds ratios and 95% confidence intervals of a CMR score ≥ 1 were 14.61 (13.31, 16.04) for men and 5.46 (4.06, 7.36) for women, and the age-adjusted probability of a CMR score ≥ 3 was 31.7% for men and 31.3% for women. Conclusions:QCT-derived VAT is closely related to CMR. The findings suggest that measurement of visceral fat is recommended for the management of abdominal obesity in subjects who agree to undergo lung cancer screening via low-dose CT without additional radiation exposure.

Objective:To investigate the effects of riboflavin-ultraviolet A scleral collagen cross-linking on the retina under different irradiation time, and to determine the safe irradiation time.Methods:Sixty healthy New Zealand white rabbits were randomly divided into control group (0 minute group), 10 minutes group, 20 minutes group, 30 minutes group and 40 minutes irradiation group according to the irradiation time, with 12 rabbits in each group.The left eye was irradiated with riboflavin-ultraviolet A scleral collagen (370 nm, 10 mW/cm 2). The histopathological change of retina was observed by light microscope and transmission electron microscope and compared among different groups.The concentration of MDA and the activities of SOD, CAT and GSH-Px in retinal tissue were detected by corresponding kits.The expression levels of SOD and CAT proteins in retinal tissue were detected by Western blot method.The study protocol was approved by the Binzhou Medical University Laboratory Animal Ethical Committee (No.2017-80). The use and care of animals complied with the statement of ARVO and the Regulation on the Management of Laboratory Animal Quality of China. Results:Under the light microscope, the structure of the retinas in the control group was orderly arranged.Under the transmission electron microscope, the lamellar structure in the inner segment and the mitochondrial structure in the outer segment of the photoreceptor cells were intact, and the mitochondrial ridge was continuous in the control group.There was no obvious difference in retinal morphology between the 10 minutes irradiation group and the control group under both the light microscope and the transmission electron microscope, and the retinal damage became more severe with the prolongation of irradiation time.The concentration of MDA in the retina of each group was elevated gradually with the increase of irradiation time, and the difference was statistically significant ( F=65.25, P<0.05). The concentration of MDA was (11.31±1.84), (14.94±1.04)and (18.25±1.42)nmol/mgprot in the 20 minutes, 30 minutes and 40 minutes irradiation groups respectively, which were significantly higher than (1.13±0.02)nmol/mgprot in the control group (all at P<0.05). The MDA concentration in 20 minutes, 30 minutes and 40 minutes irradiation groups was increased successively, showing statistically significant differences (all at P<0.05). With the prolongation of irradiation time, the activities of SOD, CAT and GSH-Px as well as the expression levels of SOD and CAT proteins were significantly decreased gradually ( F=44.09, 34.18, 35.60, 115.75, 78.86; all at P<0.05). The differences between the control group and 20 minutes, 30 minutes, 40 minutes irradiation groups, and the differences among 20 minutes, 30 minutes, 40 minutes irradiation groups were statistically significant (all at P<0.05). Conclusions:Riboflavin-ultraviolet A 10 mW/cm 2 scleral collagen cross-linking irradiation for 10 minutes is safe.Excessive irradiation time can cause damage to the retina of rabits.

Objective To explore the job satisfaction of the staff in Pharmacy Intravenous Admixture Services (PIVAS), and analyze its status quo and influencing factors. Methods From March to May 2018, totally 105 PIVAS subjects were selected from 4 Class Ⅲ Grade A teaching hospitals in Harbin by random sampling and investigated with Minnesota Satisfaction Questionnaire (MSQ) for their job satisfaction. Data were collected through questionnaire survey, and the influencing factors to the job satisfaction was analyzed. Totally 105 questionnaires were distributed in this survey, and 98 valid questionnaires were recovered, accounting for an effective recovery rate of 93.33％. Results The overall standardized score of MSQ in the 98 PIVAS staff was (4.09±0.57), including (4.13±0.59) for internal satisfaction and (4.03±0.65) for external satisfaction, and the difference was statistically significant (t=2.217,P < 0.05). Multivariate linear regression analysis revealed that marital status and working years were the influencing factors of job satisfaction of the PIVAS staff. Conclusions The external satisfaction of the PIVAS staff is lower than their internal satisfaction, and the satisfaction of married and veteran employees is relatively low. It is recommended that the managers of PIVAS should actively handle the relationship between staff and focus on the job satisfaction of the married staff and staff with long working years.

Objectives: To explore and summarize the beneficial effects of a traditional Chinese medicine prepara-tion, Tripterygium glycosides tablets (TGT), in rheumatoid arthritis (RA) animal models of neo-vascularization, and to provide a reference for future clinical applications and research on its pharmacologic mechanism.Methods: We searched the databases PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, VIP, Wan Fang and SinoMed (China Biomedical Document Service System) to identify studies of TGT with outcome indicators of angiogenesis-related factors that were published before April 2020. Subgroup analysis and meta-regression were performed for dosage and duration of TGT. Statistical tests and subgroup analysis were conducted using RevMan 5.3, and meta-regression and sensitivity analysis were conducted using STATA/SE 15.0. Results: Fourteen studies of TGT in RA rats were included in this analysis. Treatment with TGT signifi-cantly reduces synovial microvessel density and the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2, hypoxia inducible factor α, c-Fos, c-Jun, angiopoietin-1 and angiopoietin-2 compared with control groups (P < .05). Subgroup analysis did not show a significant association of the mRNA levels of VEGF in synovium, assessed using quantitative real-time PCR, with duration or dosage of TGT. Meta-regression analysis also indicated that the effects of dosage and duration were not significantly associated with differences in VEGF mRNA levels. Sensitivity analysis on VEGF mRNA levels did not fundamentally change the results. Conclusions: TGT can reduce synovial neovascularization by decreasing synovial microvessel density and expression of VEGF, VEGF receptor 2, hypoxia-inducible factorα, c-Fos, c-Jun, Ang-1 and Ang-2, thereby suppressing pannus formation and bone destruction in rat models of RA. Additional well-designed studies are required to confirm these findings.

Objective: To study infection of coxsackievirus A6 (CV-A6) in Mongolian gerbils. Methods: To screen the optimal ages of Mongolian gerbils, five groups with different ages were infected with 1×10⁵ TCID₅₀ dose of CV-A6 XS45 strain by intraperitoneal, and symptom scores of Mongolian gerbils were collected. Then to estimate the dose-effect, three doses of virus were injected to the Mongolian gerbils. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry(IHC) were used to determine virus load and tissues infection in muscle, brain and intestinal tract. Results: Mongolian gerbils infected with 1×10⁵ TCID₅₀ dose CV-A6 consistently exhibited clinical signs, and the morbidity (death) rates of five age groups were up to 100%. There was a positive correlation between the trend of symptom scores changes and ages. The morbidity (death) rates of three doses (1×10³ TCID₅₀, 1×10⁴ TCID₅₀, 1×10⁵ TCID₅₀) also were up to 100% in 28 days Mongolian gerbils. The correlation between the trend of symptom scores changes and doses were negative. Virus loads were detected in muscle, brain and intestinal tract of pathogenesis animal. The virus loads of muscle were higher than others. IHC results showed virus infection and cytopathic effects in three tissues. Conclusions Mongolian gerbils had high susceptibility to CV-A6, and were best for animal model of CV-A6 infection.

Objective To compare the efficacy of percutaneous transforaminal endoscopic discectomy with minimally invasive ozone therapy in the treatment of lumbar disc herniation combined with lumbar canal stenosis. Methods The clinical data of 90 patients with lumbar disc herniation combined with lumbar canal stenosis from May 2015 to May 2017 were analyzed retrospectively. The patients were divided into 2 groups according to the method of operation, control group (45 patients received minimally invasive ozone therapy), and observation group (45 patients received percutaneous transforaminal endoscopic discectomy). The basic surgical conditions, visual analog score (VAS), Oswestry dysfunction index (ODI), Japanese Orthopedic Association (JOA) score and efficacy were compared between 2 groups.Results The operation time in observation group was significantly longer than that in control group:(81.93 ± 17.02)min vs.(42.41 ± 15.69)min,postoperative hospitalization time was significantly shorter than that in control group: (1.27 ± 1.05) d vs. (4.29 ± 2.03) d, and there were statistical differences(t=-9.571 and 3.742,P<0.01).The VAS 1 week and 1 month after operation in observation group was significantly lower than that in control group:(4.29 ± 1.39)scores vs.(5.91 ± 1.51) scores and(2.53 ± 0.69)scores vs.(3.25 ± 0.94)scores,and there was statistical difference(P<0.01 or<0.05).The ODI and JOA score 3 months after operation in observation group were significantly better than those in control group: (13.24 ± 5.86) scores vs. (27.83 ± 8.91) scores and (24.24 ± 3.09) scores vs. (20.95 ± 6.25) scores, and there were statistical differences (P<0.01). The eligible rate in observation group was significantly higher than that in control group: 86.67%(39/45)vs.68.89%(31/45),and there was statistical difference(χ2=4.114,P<0.05).Conclusions Percutaneous transforaminal endoscopic discectomy compared with minimally invasive ozone therapy for lumbar disc herniation combined with lumbar canal stenosis is more effective,with shorter postoperative length of stay,more obvious pain relief and more quick lumbar function recovery after operation.