Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics， surgery， radiotherapy， or hormone therapy. The treatment process has limitations such as multidrug resistance， non-selective targeting of cancer cells， and drug toxicity. With the development and application of traditional Chinese medicine （TCM）， Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation， differentiation， and metastasis， and avoid drug resistance， serving as the focus of current tumor treatment research. Hedysari Radix， one of the genuine medicinal materials in Gansu province， is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation， immune regulation， anti-oxidation， prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties， Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity， scavenging free radicals， and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer， bladder cancer， gastric cancer， breast cancer， and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research， this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis， blocking cell cycle， inhibiting tumor cell proliferation， migration， and invasion， regulating micro mRNA （miRNA）， inducing cell autophagy， enhancing immune regulation， as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics， and systematically explained the anti-tumor mechanism of Hedysari Radix active components， aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.

【Objective】 To evaluate and analyze the impact of COVID-19 epidemic on inventory of red blood cells (RBCs)in local and municipal blood stations in China, and to provide reference for the management of public health emergencies. 【Methods】 Relevant data from 2018 to 2021 were collected, and the differences in the volume of qualified RBCs, the usage efficiency of inventory RBCs, the average daily distribution of RBCs,the blood distribution rate of RBCs prepared by 400 mL whole blood, the difference in the average storage days of RBCs at the time of distribution, the average daily inventory of RBCs and the time of the average daily inventory of RBCs to maintain the distribution in 24 local and municipal blood stations in China during the COVID-19 epidemic and non-epidemic periods were retrospectively analyzed. 【Results】 Compared with non-epidemic periods, the volume of qualified RBCs [(117 525.979 ±52 203.175)U] and the average daily distribution of RBCs [( 156. 468 ± 70. 186) U ] increased significantly, but the usage efficiency of inventory RBCs decreased(97.24%±0.51%) significantly (P<0.05).There was no significant difference in the blood distribution rate of RBCs prepared by 400 mL whole blood(73.88%±20.30%), the average storage days of RBCs distribution(13.040 ±3.486), the average daily stock quantity of RBCs[(2 280.542 ±1 446.538) U ] and the time of the average daily inventory of RBCs to maintain the distribution[(15.062 ±7.453) d] (P>0.5). 【Conclusion】 During the COVID-19 epidemic, the inventory management of RBCs operated well, the overall inventory remained relatively stable, the stock composition and storage period showed no significant change.

Objective:To evaluate the prognostic value of amplitude-integrated electroencephalogram(aEEG) on predicting long-term neurodevelopmental outcome of preterm infants.Methods:Literatures were searched in PubMed, the Cochrane library, Web of science, Wanfang database, CNKI and CBM database from inception to August, 2020.The studies which investigated the prognostic value of aEEG on neurodevelopmental outcome of preterm infants were included.Articles screening, data extraction and quality assessment were accomplished by two investigators independently, and statistical analyses were performed by Meta-disc1.4.Results:Six studies were included with 557 cases.The Meta-analysis revealed that the pooled sensitivity was 0.81 (95% CI 0.75-0.87), specificity was 0.68 (95% CI 0.63-0.73), positive likelihood ratio was 2.32(95% CI 1.52-3.52), negative likelihood ratio was 0.27(95% CI 0.19-0.37)and the area under the curve of summary receiver operating characteristic curve was 0.79(95% CI 0.75-0.82). Burst-suppression, continuous low voltage and flat trace were regard as a index of poor neurodevelopmental prognosis. Conclusion:aEEG is a valuable tool for predicting the outcome of long-term neurodevelopment in preterm infants.

Objective:To explore the range of medical reference value of thyroid hormone of pregnant women in early pregnancy in Jinan after adjustment of salt iodine content, so as to provide basis for clinical diagnosis and treatment of thyroid diseases of pregnant women in early pregnancy.Methods:A prospective study was conducted in 560 pregnant women in early pregnancy (0-13 weeks) who had underwent prenatal examination and thyroid function testing in Shandong Provincial Maternal and Child Health Care Hospital from January to December 2018. At the same time, 100 healthy non-pregnant women who were examined in the Health Examination Center of Shandong Provincial Maternal and Child Health Care Hospital were selected as the control population. Urine samples of pregnant women in early pregnancy were collected, and urinary iodine content was detected by arsenic cerium catalytic spectrophotometry. Venous blood samples were collected from pregnant women in early pregnancy and control population, the serum levels of free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were detected by electrochemiluminescence (ECL), and the medical reference values of FT 3, FT 4 and TSH were established. Results:The median urinary iodine of pregnant women in early pregnancy was 162.21 μg/L, which was in the appropriate level of iodine. After the adjustment of salt iodine content, the medical reference values of FT 3, FT 4 and TSH in pregnant women in early pregnancy were 3.86-6.15 pmol/L, 12.56-22.16 pmol/L and 0.01-3.48 mU/ L, respectively; and the medical reference values of FT 3, FT 4 and TSH in control population were 3.55-6.05 pmol/L, 9.93-20.58 pmol/L and 0.54-5.92 mU/L, respectively. Conclusions:The iodine nutrition of pregnant women in early pregnancy in Jinan is appropriate after the adjustment of salt iodine content. The medical reference values of FT 3, FT 4 and TSH in pregnant women in early pregnancy are different from those in the healthy non-pregnant women. Therefore, it is of clinical significance to establish a medical reference value range of thyroid hormone for pregnant women in early pregnancy.

Objective To analyze the infection features,risk factors,and the relationship with the efficacy in patients with acute leukemia during initial induction chemotherapy.Methods The clinical data of 200 patients with newly diagnosed acute leukemia from January 2015 to February 2016 in the Second Hospital of Shanxi Medical University were retrospectively analyzed.Results The infection rate of patients with acute leukemia under induction chemotherapy was 84.0％ (168/200).Among 168 patients with infection,159 cases (94.6％) had known infection sites,the top three infection sites were the lungs,gastrointestinal tract and the oral cavity.Total 213 strains of pathogens were identified,Gram-negative bacilli accounted for 39.0％ (n =83),Gram-positive cocci for 34.3％ (n =73),fungi for 23.5％ (n =50) and the virus for 3.3％ (n =7).Multivariate regression analysis showed that agranulocytosis was the independent risk factor for acute leukemia patients during induction chemotherapy (OR =14.370,95％ CI:2.576-116.518,P ＜ 0.01).The rate of complete remission (CR) and CR with incomplete hematologic recovery (CRi) in infection group was 74.4％ (125/168),and the rate of CR + CRi in non-infected group was 87.5％ (28/32),and there was no significant difference between the two groups.(χ2 =2.564,P =0.109).Conclusion During the induction therapy for acute leukemia patients,the rate of infection and the rate of fungal infection are high;lung is the most common site,Gram-negative bacteria is more common;agranulocytosis increases the chance of infection;and the infection may not affect the disease remission rate.

Objective:To investigate and compare the effects of water extracts of Whitmania pigra Whitman and Hirudinaria ma-nillensis Lesson on the angiogenesis of Tg (kdrl:mCherry) zebrafish. Methods:The zebrafish embryos 6-8 hours after fertilization (6-8hpf) were transferred to the culture medium containing Whitmania pigra Whitman or Hirudinaria manillensis Lesson extract at different concentrations, and the culture medium containing the drugs was replaced every 24 h. And then, at 72 hpf, the larvalmorphology and intersegmental vessels were observed under a microscope. The hatchability of 48-and 72-hpf embryos, and the number of intersegmen-tal vessels and the heart rate of 72-hpf juveniles were measured. Results:Compared with the control group, when the concentration of Whitmania pigra Whitmanis was higher than 30μg· ml-1 , and the concentration of Hirudinaria manillensis Lesson was higher than 20μg· ml-1, the number of intersegmental vessels was significantly reduced (P<0. 01). Compared with the control group, at 48 hpf, when the concentration of the drug groups was higher than 40 μg· ml-1 , the hatchability of the two groups significantly decreased ( P<0. 01);at 72 hpf, the hatchability of Whitmania pigra Whitman decreased significantly at the concentration of 100 μg·ml-1 (P<0.01), while the hatchability of Hirudinaria manillensis Lesson decreased significantly at the concentration of 80 μg· ml-1(P <0. 01). There was no obvious yolk sac edema, pericardial edema and spine curvature in the two groups. The heart rate decreased sig-nificantly (P<0. 01), while was still within the normal range. Conclusion:Both Whitmania pigra Whitman and Hirudinaria manillen-sis Lesson have notable anti-angiogenic activity, and the anti-angiogenesis activity of Hirudinaria manillensis Lesson is stronger. They both have effects on the development of zebrafish embryos, while the toxicity is not obvious.

Objective To identify the epidemiological changes in invasive fungal infection (IFI) in a neonatal intensive care unit (NICU) to provide information for prevention and treatment of IFI.Methods A total of 102 cases who were diagnosed with IFI among 42 187 neonates hospitalized in the NICU of Affiliated BaYi Children's Hospital,Chinese People's Liberation Army General Hospital from January 1,2009 to December 31,2014 were enrolled in this study.Since January 1,2012,the divisions of our NICU were more specific and intravenous fluconazole was administered as a routine preventive measure for high-risk infants.Clinical information of the IFI cases including general features,incidence,distribution of pathogens and drug (Amphotericin B,Fluconazole,Flucytosin,Itraconazole and Voriconazole) sensitivity were analyzed between former period (January 1,2009 to December 31,2011) and latter period (January 1,2012 to December 31,2014) by Chi-square test.Results The total incidence of IFI was 2.42‰ (102/42 187),and among the 102 IFI cases,73.5％ (75/102) were preterm infants and 75.5％ (77/102) were low birth weight infants.The incidence ofIFI in the latter period was lower than that in the former period [1.8‰ (48/26 046) vs 3.3‰ (54/16 141),x2=9.329,P＜0.01].The incidences of IFI in neonates with gestation age ＜28,≥ 28-＜32 and ≥ 32-＜37 weeks in latter period were decreased as compared with those in former period [10.6 ‰ (3/284) vs 76.9 ‰ (9/117),x2=12.569;6.1‰ (13/2 134) vs 21.9‰ (28/1 277),x2=16.868;1.4‰ (12/8 706) vs 1.9‰ (10/5 256),x2=7.165] (all P＜0.01).Altogether 103 pathogen strains were identified from 102 IFI cases as one Candida parapsilosis strain and one Laurent cryptococcus strain were both isolated from one patient.The most prevalent three pathogens were Candida albicans [51.5％ (53/103)],Candidaparapsilosis [24.3％ (25/103)] and Candida glabrata [8.7％ (9/103)].The isolated rates of Candida albicans and Candida glabrata strains in the latter period were higher than those in the former period [63.3％ (31/49) vs 40.7％ (22/54),x2=5.218;18.4％ (9/49) vs 0.0％ (0/54),x2=10.868],while the isolated rate of Candida parapsilosis strain was lower in the latter period than that in the former period [12.2％(6/49) vs 35.2％(19/54),x2=7.355] (all P＜0.05).All pathogen strains were sensitive strains except one Candida krusei strain which was isolated in the former period and was resistant to Fluconazole.Conclusions Premature infants born at lower gestational ages or with low birth weights are still at high-risk of IFI,but the incidence of IFI has declined in recent years.Routine administration of fluconazole in high-risk infants in NICU could prevente IFI without increasing drug resistance.Candida albicans is the predominant pathogen ofIFI.

Objective To evaluate the effects and mechanisms of bovine lactoferrin(bLF)on cell viability,proliferation,and the protective roles in intestinal epithelial cell-6(IEC-6)treated by lipopolysaccharide(LPS).Methods The rat jejunum epithelial cell lines IEC-6 were cultured in vitro.The effects of bLF on cell viability and proliferation in IEC-6 cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)assay and 5-Bromo-deoxyuridine(Brdu)assay,respectively.Inflammatory cytokines and their mRNA of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interleukin-8(IL-8)were analyzed by real-time PCR and enzyme-linked immunosorbent assay(ELISA).Western blot was used to measure the levels of mitogen-activated protein kinase(MAPK)activation and nuclear factor kappa β(NF-κB)nuclear translocation.Results Dose dependent effects of bLF on cell viability and proliferation were observed in IEC-6 cells in vitro(F=3.825,5.861,all P<0.05),especially in a dose of 100 mg/L,and bLF significantly stimulated cell viability and proliferation compared with non-treatment group(q=5.240,3.765,all P<0.05).The mRNA levels of IL-1β,IL-6 and TNF-α were decreased by co-stimulation of bLF and LPS compared with the LPS treatments alone in IEC-6 cells in vitro(q=14.28,10.12,16.45,all P<0.001).The secretion of IL-6 and TNF-α was also decreased by co-stimulation of bLF and LPS(q=15.06,6.74,all P<0.01).In vitro,bLF treatment at dose of 100 mg/L could inhibit the activation of MAPK/NF-κB signal pathway induced by LPS(q=12.96,18.54,all P<0.001).Conclusion In vitro,bLF can promote IEC-6 viability and proliferation,and have anti-inflammatory effects via inhibited activation of MAPK/NF-κB nuclear translocation.

Objective To determine the trend of emergency department (ED)mortality of a tertiary general hospital from 2004 to 2014 in order to find the factors that may impact on ED mortality.Methods Mortality in ED was estimated according to the ratio of ED visiting patients to ED deaths.And the data of all ED deaths in 2004,2009 and 2014 were collected.Variance analysis and chi-square test were used for data analysis.Results During the past decade,ED visiting patients was increased significantly by 38.0% in 2014,compared with those in 2004,and the mortality was also increased accordingly from 0.7% in 2004, to 0.9% in 2009,to 1.2% in 2014 (P <0.01).Finally,a total of 1,091 deaths occurred in these three years were included for further evaluation.There were no significant changes in average age and gender distribution,and the average age was 61.9 and the male /female ratio was 1.36∶1 during past decade.The number of adults under 40 years old (18 -39)increased from 7.5% in 2004,to 10.6% in 2009,to 14.4% in 2014 (P <0.05).Both the facilities were upgraded and the number of staffs in ED increased markedly.The cardiovascular illness,cerebrovascular diseases,and sudden death were the leading causes of ED death during past decade.The incidences of trauma and tumor remained unchanged.Average time consumed from onset of illness to arrival to ED didn’t vary significantly during past decade.The study showed no changes in use of ambulance,but remarkable increases in number of non-compliant patients or their family from 18.3% in 2004,to 25.6% in 2009,to 38.3% in 2014 (P <0.01).The percentage of patients in the night time was higher,but there were no significant changes in number of emergency patients in the night time and during holidays in the past decade,but the mean ED stay time increased obviously from 22.4 h in 2004 to 53.3 h in 2014 (P <0.05 ).Conclusions During the past decade,although ED facilities and number of staffs have been improved apparently,ED mortality rate still keeps on escalating. The increase in ED mortality rate may be related to the severely ill patients presenting to ED,the obvious decrease in compliance of patients and the prolonged ED stay time.