ObjectiveTo explore the molecular mechanism implicated in the treatment of primary myelofibrosis （PMF） using Chinese medicinal herbs （CMH） by bioinformatics and molecular dynamics. MethodsData mining was performed to find the high-frequency CMH in treating PMF between the year of 1985 and 2024 by searching CNKI， Chinese Science and Technology Journal Database （CCD）， and China Academic Journal Database （CSPD）. TCMSP， SwissTargetPrediction and related reports were used to collect the main active ingredients of high-frequency CMH and their targets. The PMF datasets GSE44426 and GSE124281 were downloaded from GEO database， and R software was used for data normalization and differentially expressed genes （DEGs） screening. Key module hub genes were obtained by weighted gene co-expression network analysis （WGCNA） analysis. The common intersection genes of active ingredient targets， DEGs and key module hub genes of CMH were selected， and the target network was generated using Cytoscape 3.9.2 software. The core target network was generated by topological analysis， while key pathways were selected by GO and KEGG pathway enrichment analysis， and protein interaction relationships were obtained from the String database， so as to construct drug-ingredient-target network and protein interaction network （PPI） relationship diagrams. Discovery Studio 2020 software was used to perform molecular docking， and the GROMACS program was used to perform molecular dynamics simulation. ResultsA total of 21 prescriptions were collected involving 121 herbs. There were 9 herbs with a frequency ≥10 times， which were Danshen （Radix et Rhizoma Salviae Miltiorrhizae）， Huangqi （Radix Astragali）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Danggui （Radix Angelicae Sinensis）， Dangshen （Radix Codonopsis）， Gancao （Radix et Rhizoma Glycyrrhizae）， Baishao （Radix Paeoniae Alba）， Fuling （Poria） and Shudihuang （Radix Rehmanniae Praeparata） from high- to low-frequency. A total of 98 active ingredients and 1125 potential targets were obtained from 9 high-frequency CMH. GSE44426 and GSE124281 data sets screened out 24 gene samples， including 14 of the healthy control group and 10 of the PMF group， and identified 319 DEGs between the two groups， including 122 up-regulated genes and 197 down-regulated genes. WGCNA screened out 24 co-expression module genes and found that the five modules closely related to the onset of PMF were MEpink， MEdarkred， MEblack， MEgrey， and MEturquoise， involving 7112 key module hub genes. The GO and KEGG enrichment analyses indicated that lipids and the atherosclerosis pathways were mainly involved in the mechanism of above high-frequency CMH in treating PMF， which included six hub protein targets： HSP90AA1， HSP90AB1， SRC， MAPK1， IL1B and IL10. From the drug-ingredient-target network， seven active ingredients of CMH targeting at these six hub targets were found， including verbascoside， verbascos isoflavone， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The molecular docking and molecular dynamics analyses showed that the key CMH were Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and among the seven active ingredients， calycosin had the highest binding affinity with HSP90AB1. ConclusionThe main CMH for the treatment of PMF may be Shudihuang， Huangqi， Baishao， Danshen， Gancao and Fuling， and the active ingredients include verbascoside， verbascos isoflavones， kaempferol， luteolin， naringenin， quercetin and pachymic acid. The relevant targets are HSP90AA1， HSP90AB1， SRC， MAPK1， IL-10， and IL-1β， and the most critical pathways are lipid and atherosclerosis pathways.

ObjectiveTo understand the cooperative work and mechanism in the corona virus disease 2019 containment action by the support-to-Hebei epidemiological investigation group formed by five provinces， summarize the existing challenges， and discuss the relevant mechanism， so as to provide evidence for future support actions. MethodsA questionnaire survey was used to investigate the members from five provinces of the support-to-Hebei epidemiological investigation team. The content included basic information， work situation， problems in cooperative work， and suggestions in support mechanisms. ResultsA total of 104 questionnaires were issued， of which 101 valid questionnaires were collected with an effective response rate of 97.12%. The proportions of respondents who participated in the epidemic-related data preparation， case investigation， technical training， supervision of key venues， and specimen collection was 93.07%， 85.15%， 81.19%， 65.35%， and 44.55%， respectively. The respondents believed that information sharing channel of local epidemic situation was blocked （95.05%）， coordination mechanism among local departments was insufficient （84.16%）， communication and coordination mechanism among the dispatch institutions， support team， and local departments was unperfect （84.16%）， management of the dispatch institutions to the support team was relatively loose （79.21%）， dispatch institutions failed to make full use of professional advantages of the support team （72.28%）， and majority of the support team members engaged in a single profession （59.41%）. The respondents suggested that local departments should improve the information sharing mechanism （95.05%）， strengthen communication and coordination among the dispatch institutions， support team， and local departments （92.08%）， and dispatch institutions should clarify the tasks and responsibilities of the support team （91.09%）， formulate cross-regional emergency support plans （87.13%） and evaluation plans of support action （72.28%）. ConclusionIn order to ensure the efficiency and accuracy of future support actions， it is necessary to improve the mechanism of emergency coordination， communication and matching， response procedures， team management， and support evaluation.

Objective:To explore the mediating effect of nurses′ self-efficacy in palliative care between the past behavioral experience of end-of-life care and core competence, and provide theoretical reference for improving the core competence of clinical nurses in palliative care.Methods:579 clinical nurses from 2 tertiary general hospitals in Shandong Province were investigated by convenience sampling method using general information questionnaire, nurses′ self-efficacy questionnaire for palliative care and palliative care nurses′ core competency questionnaire. The data were analyzed by SPSS 25.0.Results:The total score of core competence of hospice care of 579 nurses was (71.41 ± 22.74), nurses′ self-efficacy of palliative care was positively correlated with their core competence ( r = 0.648, P<0.01), past behavior experience was positively correlated with self-efficacy ( r = 0.479, P<0.01), positively correlated with core competence ( r = 0.427, P<0.01). Nurses′ self-efficacy of palliative care played a partial mediating role between the pastbehavioral experience and core competence, which accounted for 64.67% of the total effect. Conclusions:The past behavioral experience of end-stage nursing can directly or indirectly affect the core competence of nurses in palliative care through self-efficacy. It can improve the core competence of palliative care by taking active measures to enrich the past behavioral experience of end-of-life care and improve self-efficacy.

Microbial cell factories capable of producing valuable chemicals from renewable feedstocks provide a promising alternative towards sustainability. However, environmental stress remarkably affects the performance of microbial cell factories. By extending the chronological lifespan of microbial cells, the performance of microbial cell factories can be greatly improved. Firstly, an evaluation system for chronological lifespan and semi-chronological lifespan was established based on the changes in survival rates. Secondly, the addition of anti-aging drugs such as cysteine, carnosine, aminoguanidine and glucosamine increased the chronological lifespan of E. coli by 80%, 80%, 50% and 120%, respectively. Finally, we demonstrated that extending the chronological lifespan of E. coli increased the yield of metabolites produced by E. coli cell factories with endogenous (lactic acid and pyruvic acid) or exogenous (malic acid) metabolic pathway by 30.0%, 25.0%, and 27.0%, respectively. The strategy of extending chronological lifespan of E. coli provides a potential approach for enhancing the performance of microbial cell factories.
Escherichia coli/genetics* ; Lactic Acid ; Longevity ; Metabolic Engineering ; Metabolic Networks and Pathways

Alpha-keto acid is a bifunctional organic compound containing both carboxyl and ketone groups, and widely applied in the industries of food, pharmaceutical and cosmetics. Based on the demand of eco-friendly process, safety and sustainable development, production of α-keto acids by enzymatic conversion technology has been paid more and more attention. In this article, we review the status of α-keto acids biosynthesis from three aspects: enzymatic screening, enzymatic modification and optimization of enzymatic conversion conditions. Meanwhile, we also indicate future research directions for further improving α-keto acids production.
Keto Acids ; metabolism

L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.

Objective To explore the expressions of growth factor receptor binding protein 2 -associated bin-ding protein -1 (Gab -1 )and glioma -associated oncogene homologue -1 (Gli -1 )in pediatric medulloblastoma,and to analyze their correlation between clinical and pathological characteristics and prognosis in pediatric medulloblastoma. Methods Elivision immunohistochemistry was used to detect the expressions of Gab -1 and Gli -1 protein in tissue microarray of 40 paraffin embedded pediatric medulloblastoma specimens.Chi -square test or Fisher exact test was used to analyze the correlation between Gab -1 and Gli -1 protein expressions with gender,age,tumor location and pathological subtypes.Follow -up data were handled by using Kaplan -Meier survival analysis and Cox regression anal-ysis.Results Positive expression ratios of Gab -1 and Gli -1 protein in 40 pediatric medulloblastoma were 35.0%and 55.0%,respectively.The positive expression rate of Gab -1 in medulloblastoma tissues had no statistical signifi-cance between different genders[male:30.4%(7 /23 cases)vs.female:41 .2%(7 /17 cases)],age[<3 years old:40.0%(6 /15 cases)vs.≥3 years old:32.0%(8 /25 cases)],tumor location[cerebellum:25.0%(5 /20 cases)vs. the fourth ventricle:45.0%(9 /20 cases)]and pathological subtype[classical type:40.7%(11 /27 cases)vs.desmo-plastic /nodular type:50.0%(5 /10 cases)vs.anaplastic /large cell type:66.7%(2 /3 cases)](χ2 =0.496,0.264, 1 .758,3.289,all P >0.05).There were statistical differences of positive expression rate of Gli -1 protein in different age groups[<3 years old:80.0%(12 /15 cases)vs.≥3 years old 40.0%(10 /25 cases)],different pathological sub-types[classical type:40.7%(11 /27 cases)vs.desmoplastic /nodular type:90.0%(9 /10 cases)vs.anaplastic /large cell type:66.7%(2 /3 cases)](χ2 =6.061 ,7.333,all P <0.05 ).There was no statistical difference in positive expression rate of Gli -1 protein between different gender[male:60.9%(14 /23 cases)vs.female:47.1 %(8 /17 cases)]and different tumor location [cerebellum:55.0% (11 /20 cases)vs.the fourth ventricle:55.0% (11 /20 cases)](χ2 =0.753,0.000,all P >0.05).Kaplan -Meier survival analysis showed that the age,the expressions of Gab -1 and Gli -1 protein were correlated with prognosis of pediatric medulloblastoma(all P <0.05).Cox regression indicated that the age,pathological subtypes and the expression of Gli -1 protein were independent prognostic indicators in pediatric medulloblastoma(all P <0.05).Conclusion Expression of Gab -1 and Gli -1 protein is significantly correlated with the prognosis of medulloblastoma,and the positive expression is a marker of unfavorable prognosis.

Aim To explore whether the polypeptide vaccines CKL9 and YL20 can induce immune response and anti-tumor effect on HER-2 (+) tumors in vitro and in vivo, and to provide suggestions for clinical use.Methods The proliferation of specific lymphocytes and cytotoxic T lymphocyte activity(CTL) stimulated by CKL9 and YL20 were studied with CCK-8 assay and LDH assay, and the antitumor activity of CKL9 and YL20 was evaluated in vivo.Results The lymphocyte proliferation was promoted by incubation with CKL9 and YL20, and the relative increase of cells was 11.1% and 16.7% respectively at the concentration of 50 mg·L-1 of CKL9 and YL20.The LDH assay confirmed the CTL effect induced by CKL9 and YL20 on HER2-positive tumor cells, not on HER2-negtive tumor cells.With an effector-target ratio of 80 ∶1, the inhibition of tumor cell by cytotoxic T lymphocyte stimulated by CKL9 and YL20 could reach 89.8% and 84.3%, respectively.The HER2(+) tumor cell N87 transplanted in Babes mice was inhibited by pre-immune polypeptide CKL9 and YL20.Conclusion The HER2-specific polypeptide vaccines CKL9 and YL20 could induce persistent specific CD4 and CD8 T cell immune and inhibit the growth of HER2 positive tumor cells.

Objective To learn the change of serum thymidine Kinase 1(TK1) level in the treatment process of the early cure nasopharyngeal carcinoma patients and its relationship to pathological features .Methods From January 2010 to December 2013 ,35 cases of nasopharyngeal carcinoma patients were collected into our study ,20 cases of nasopharyngeal inflammation patients were chosen as the control .Serum TK1 level in the 2 groups was compared before and after treatment .Results TK1 in control group had no significant differences before and after treatment (P>0 .05) .Compared with the control group ,serum TK1 in nasopharyngeal carcinoma group were higher before and after radiotherapy (P<0 .05);after radiotherapy ,serums TK1 in nasopharyngeal carcinoma group were lower(P<0 .05) .Before and after radiotherapy ,serum TK1 Ⅰ and Ⅱ stage were lower than in Ⅲ and Ⅳ stager(P<0 .05) ,lymph node metastasis group were higher than no lymph node metastasisr (P<0 .05) ,TK1 had higher expression in TNMⅣ than TNM Ⅱ(P<0 .05) ,compared with lymph node metastasis and cervical nerve violated groups ,TK1 expression was higher in none lymph node metastasis and none cervical nerve violated groups (P<0 .05) .Conclusion TK1 can reflect the tumor load and proliferative activity of nasopharyngeal carcinoma ,which could be as a factor in nasopharyngeal carcinoma diagnosis ,monitoring and prognosis .

Objective Pancreatic duodenal homeobox-1 ( PDX-1) plays an important role in the occurrence and development of diabetes.More importantly,its potential application in insulin resistance (IR) improvement is attracting further attention .Berberine has been shown to improve glucose metabolism and insulin resistance .In this study,rat models of type 2 diabetes mellitus ( T2DM) were established by combination of intraperitoneal injection of low -dose streptozotocin and highg-lucose-high-fat diet induction .The effect of berberine on fasting glucose , fasting serum insulin , homeostasis model assessment of insulin resistance ( HOMAI-R) , and ex-pression of PDX -1 of islet in T2DM rats were analyzed .The present study aimed to evaluate the anti-diabetic efficacy of berberine and study the mechanism of its preliminary therapeutic effects .Methods Twenty healthy adult male Sprague Dawley ( SD) rats were di-vided by random number table into the normal control group ( n =6) feeding with a standard diet ,and the experimental group ( n =14 ) given an intraperitoneal injection of streptozotocin .The rats with fasting blood glucose ( FBG) greater than 13.8 mmol/L were ran-domly divided into diabetes mellitus group feeding high sugar high fat diet for two weeks and then continuing with a standard diet , and the berberine group given berberine [180 mg /(kg· d)] every day.The normal control group and diabetes mellitus group were given physiological saline for every day 6 weeks.At the end of 6th week, the rats were executed , and the levels of fasting glucose, fasting se-rum insulin, HOMA-IR, and expression of PDX-1 in pancreas islet of each group were detected .The expression of PDX1-in pancreas islet was examined by immunohistochemistry .The image pro plus 6.0software was used to calculate the integrated optical density ( IOD) of positive expression .Results Compared with the normal control group , FBG, fasting insulin levels ( FINS) , and HOMA-IR of the diabetes mellitus group and berberine group were significantly increased ( P <0.05 ) .Compared with the diabetes mellitus group, FBG, FINS, and HOMA-IR of the berberine group were statistically significantly decreased [ ( 13.11 ±6.87 ) mmol/L vs (18.45 ±4.69) mmol L/, (2.58 ±0.34) μIU/ml vs (2.98 ±0.40) μIU/ml, 1.60 ±0.91 vs 2.75 ±0.28, P <0.05].Compared with the normal control group , the expression of PDX-1 of the islet in the diabetes mellitus group and berberine group was statistically significantly decreased ( P <0.05).After treatment with berberine, FBG, FINS, HOMA-IR, and IOD of PDX-1 in pancreas islet of berberine treatment rats were significantly increased compared with the diabetes mellitus group ( 9.14 ±1.51 vs 6.79 ±0.98 , P <0.01 ) .Conclusions The increases of PDX-1 in islet may be one of the mechanism in the improvement of hyperglycemia .