Angelicae Sinensis Radix (AS) is reproted to exert anti-depression effect (ADE) and nourishing blood effect (NBE) in a rat model of depression. The correlation between the two therapeutic effects and its underlying mechanisms deserves further study. The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics, network pharmacology and molecular docking. According to metabolomics analysis, 30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression. Furthermore, principal component analysis and correlation analysis showed that glutathione, sphinganine, and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators, indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS. Then, a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis, where a total of 107 pathways were collected. Moreover, 37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer (UPLC-Triple-TOF/MS) in AS extract that passed the filtering criteria were used for network pharmacology, where 46 targets were associated with the ADE and NBE of AS. Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS. Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins (PIK3CA and PIK3CD) in sphingolipid metabolism. Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism. Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.
Rats ; Animals ; Rats, Sprague-Dawley ; Molecular Docking Simulation ; Network Pharmacology ; Drugs, Chinese Herbal/chemistry* ; Metabolomics/methods* ; Mass Spectrometry

Objective:To explore the relationship among social support, discharge readiness and quality of life in elderly patients with hip fracture, and to analyze the mediating effect of discharge readiness on social support and quality of life.Methods:This study was a cross-sectional study. From June 2020 to July 2021, 220 elderly patients with hip fracture who underwent surgical treatment in the Trauma Center of the Shandong Provincial Hospital Affiliated to Shandong First Medical University were selected as the research object. The patients were surveyed using the General Information Questionnaire, Social Support Rate Scale (SSRS) , Readiness for Hospital Discharge Scale (RHDS) , and the 12-item Short From Health Survey (SF-12) .Pearson correlation was used to explore the correlation among variables, and AMOS 23.0 software was used to construct structural equation model, and Bootstrap method was used to test the mediating effect. A total of 220 questionnaires were distributed, and 193 valid questionnaires were recovered, with a valid rate of 87.73 % (193/220) .Results:Among 193 elderly patients after hip fracture surgery, the total scores of RHDS, SSRS and SF-12 were (79.39±6.42) , (38.62±6.74) , and (65.39±9.28) , respectively. Social support was positively correlated with discharge readiness ( r=0.39, P<0.01) , discharge readiness was positively correlated with quality of life ( r=0.67, P<0.01) , and social support was positively correlated with quality of life ( r=0.56, P<0.01) . The results of path analysis showed that discharge readiness of elderly patients after hip fracture surgery could positively predict quality of life (β=0.54, P<0.01) , and social support could positively predict discharge readiness (β=0.23, P<0.01) and quality of life (β=0.34, P<0.01) . Discharge readiness played a partial mediating role between social support and quality of life, with a mediating effect of 0.124 2, accounting for 26.76% of the total effect. Conclusions:Discharge readiness of elderly patients after hip fracture surgery is low. Discharge readiness partially mediates the relationship between social support and quality of life. Nurses should formulate corresponding intervention measures to improve the social support and discharge readiness of elderly patients after hip fracture surgery, thereby improving their quality of life.

Objective To study the characteristics of fluid intake and central venous pressure (CVP) within 4 days after birth in very low birth weight (VLBW) premature infants complicated with bronchopulmonary dysplasia (BPD).Method From February 2015 to March 2019,VLBW preterm infants without serious complications were enrolled in two hospitals.Their CVP were measured every 4 ～ 6 hours after birth.They were assigned into BPD group and non-BPD group,and the fluid intake and CVP within 4 days after birth were compared between these two groups.Result A total of 45 VLBW preterm infants were included,including 17 in the BPD group and 28 in the non-BPD group.The fluid intake in the BPD group showed no significant difference with the non-BPD group within 4 days after birth (P ＞ 0.05).No significant correlation existed between the mean liquid intake and the mean CVP in 1 ～ 4 days after birth (r =0.093,P=0.542).From day1 to day4,the CVPs of the BPD group were (3.97 ± 0.68),(4.49 ± 0.75),(4.55 ± 0.66),(4.02 ± 1.05) cmH2O,and the non-BPD group were (3.66 ± 1.09),(3.96 ±0.76),(3.81 ± 0.69),(3.91 ± 0.65) cmH2O.The differences between the BPD group and the nonBPD group were statistically significant (P ＜ 0.05).The CVP of the BPD group was increasing from day 2 to day 3 (P ＜ 0.05).Conclusion VLBW premature infants complicated with BPD may have higher CVP at the early stage of life,which may not be related with the fluid intake.

Objective: To investigate the effects of denatured collagen type Ⅰ on differentiation of human fibroblasts into myofibroblasts. Methods: A small amount of normal skin donated by burn patients undergoing scar surgery was collected. Human fibroblasts were obtained by method of explant culture and then sub-cultured. The fourth passage of cells were used in the following experiments. (1) Fibroblasts were divided into normal collagen group and denatured collagen group according to the random number table, with 10 wells in each group. Fibroblasts in normal collagen group were cultured on normal collagen type Ⅰ coated coverslips. Fibroblasts in denatured collagen group were cultured on denatured type Ⅰ collagen coated coverslips. Expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemical method, and the percentage of PCNA positive cells was calculated. (2) Another batch of fibroblasts were grouped and treated as in (1), with 12 wells in each group. Proliferation activity of cells was determined with methyl-thiazolyl-tetrazolium colorimetry method. (3) Another batch of fibroblasts were grouped and treated as in (1), and the microfilament morphology of cells was observed by rhodamine-phalloidin staining. (4) Another batch of fibroblasts were grouped and treated as in (1). Expression of α smooth muscle actin (α-SMA) of cells was detected by immunohistochemical method, and expression of OB-cadherin of cells was detected by immunofluorescence method. (5) Another batch of fibroblasts were divided into normal collagen, denatured collagen, and common coverslips groups according to the random number table, with 6 wells in each group. Fibroblasts in normal collagen and denatured collagen groups were treated as in (1), while fibroblasts in common coverslips group were cultured on coverslips without collagen coating. Expressions of α-SMA and OB-cadherin of cells were determined with Western blotting. (6) Another batch of fibroblasts were grouped and treated as in (5), and then the mRNA expressions of collagen type Ⅰ, collagen type Ⅲ, and α-SMA of cells were determined with real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were processed with t test, one way analysis of variance, and least-significant difference test. Results: (1) The percentage of PCNA positive cells in denatured collagen group was (83±9)%, significantly higher than (29±9)% in normal collagen group (t=13.53, P<0.01). (2) The proliferation activity of fibroblasts in denatured collagen group was 0.32±0.06, significantly higher than 0.25±0.05 in normal collagen group (t=3.06, P<0.01). (3) The microfilament of fibroblasts in normal collagen group was arranged vertically and in parallel way, paralleling the long axis of cells. The microfilament of fibroblasts in denatured collagen group was denser and thicker. (4) Most fibroblasts in normal collagen group showed long shuttle-like shape typically. Morphology of fibroblasts in denatured collagen group changed, and cells were obviously spreading. Expressions of α-SMA and OB-cadherin of fibroblasts in denatured collagen group were stronger than those in normal collagen group. (5) Expressions of α-SMA of fibroblasts in denatured collagen, normal collagen, and common coverslips groups were respectively 1.69±0.41, 0.89±0.27, and 1.46±0.42. Expression of α-SMA of fibroblasts in denatured collagen group was significantly higher than that in normal collagen group (P<0.01). Expressions of OB-cadherin of fibroblasts in denatured collagen, normal collagen, and common coverslips groups were respectively 5.17±0.28, 2.21±0.10, and 4.01±0.56. Expression of OB-cadherin of fibroblasts in denatured group was significantly higher than that in normal collagen group (P<0.01). (6) There was no significant difference in mRNA expression of collagen type Ⅰ of fibroblasts in denatured collagen, normal collagen, and common coverslips groups (F=2.71, P>0.05). The mRNA expressions of collagen type Ⅲ and α-SMA of fibroblasts in normal collagen group were significantly lower than those in denatured collagen group (P<0.01). Conclusions Denatured collagen type Ⅰ may influence the activity of fibroblasts, thus inducing fibroblasts differentiating into myofibroblasts.

Objective To evaluate the clinical efficacy and analyze relevant prognostic factors of simultaneous integrated boost intensity-modulated radiation therapy ( SIB-IMRT ) for esophageal squamous cell carcinoma. Methods A total of 101 patients diagnosed with esophageal squamous cell carcinoma received SIB-IMRT from 2009 to 2015. The prescribed dose of PTV was 5040 cGy/28 times ( 180 cGy/time) and the dose for planning gross tumor volume (PGTV) was 6020 cGy/28 times (215 cGy/time) or 6160 cGy/28 times ( 220 cGy/time) simultaneously. The total treatment time was 5. 5 weeks ( once a day, 5 times a week).The adverse events, mode of treatment failure,l-,3-and 5-year local control (LC) and overall survival ( OS) rates were observed. Results The quantity of patients who completed the 1-,3-and 5-year follow-up was 101, 84 and 45, respectively. The 1-,3-and 5-year LC rates were 81. 6％,70. 4％ and 68. 4％, respectively. The 1-, 3-and 5-year OS rates were 72. 3％, 49. 4％ and 45. 2％, respectively. The median survival time was 36 months. Univariate and multivariate analyses showed that clinical staging ( stageⅠ/Ⅱ/Ⅲ) and tumor response ( complete remission/ partial remission/no remission ) were the prognostic factors of OS (P=0. 016,0. 000,0. 005,0. 000).There were no significant differences in the LC and OS between the two groups of 215 cGy and 220 cGy (P=0. 283,0. 951).The incidence rates of grade 1,2,3 acute pneumonitis were 10. 9％(11/101),2. 0％(2/101) and 2. 0％(2/101), respectively. The incidence rates of grade 1, 2, 3 acute esophagitis were 63. 4％( 64/101 ) , 10. 9％( 11/101 ) and 4. 0％( 4/101 ) , respectively. No acute esophageal perforation or hemorrhage occurred. Five patients experienced late pneumonitis ( two died) . One case developed late lemostenosis, two cases developed esophageal perforation and hemorrhage, and two patients experienced esophageal hemorrhage. The patients treated with a fractionated dose of 220 cGy had a higher incidence rate of acute pneumonitis and upper gastrointestinal adverse reactions than those receiving 215 cGy ( P= 0. 062, 0. 024 ) . The local failure and recurrence accounted for 62. 5％ of all treatment-related failures. Conclusions SIB-IMRT yields high long-term clinical efficacy and tolerable adverse events in the treatment of esophageal squamous cell carcinoma. Compared with the dose of 215 cGy, the fractionated dose of 220 cGy fails to improve LC and OS rates, whereas enhances the risk of adverse events. The clinical staging and short-term clinical efficacy are the prognostic factors of survival rate.

Objective To investigate the condition and the related influence factors of small airway function in controlled bronchial asthmatic children.Methods Children diagnosed with bronchial asthma controlled,aged 5-14 years old without gender limitation were consecutively enrolled.Survey questionnaire including asthma symptoms in the past one month and medication usage were conducted.Physical condition and lung function were examined.Results A total of 255 patients were included in this study,and 224 patients had normal small airway function in which the level of forced expiratory flow at 50％ of forced vital capacity(FVC) exhaled (FEF50),forced expiratory flow at 75％ of FVC exhaled(FEF75),maximal mid-expiratory flow(MMEF) was 87.9％ (77.0％,97.2％),73.8％ (65.6％,93.5％),and 84.9％ (76.4％,97.5％) of the predicted value,respectively.Thirty-one patients had small airway dysfunction,accounting for 12.2％ (31/255 cases),and the level of FEF50,FEF75,MMEF were 62.8％ (59.9％,65.5％),51.9％ (46.6％,55.5％),and 62.7％ (57.2％,64.4％) of the predicted value,in which FEF75 had shown more decrease than others.In small airway dysfunction group,10 patients had conducted bronchodilation testing,and improvement rate of FEF50,FEF75 and MMEF were 41.1％,47.5％ and 41.3％,and all 10 cases (100.0％) returned to normal level.No significant difference was found in gender,body mass index,atopy,disease duration,drug usage between 2 groups (all P ＞ 0.05).Conclusion In 5-14 controlled asthmatic children,12.2％ have small airway dysfunction with a certain degree of reversibility.Gender,body mass index,atopy,disease duration,drug usage are not influencing factors.

Objective To investigate the differences of clinical efficacy and untoward reaction of different chemotherapy regi‐mens for patients with malignant glioma on different expression levels of O6‐methylguanine‐DNA‐methyltransferase(MGMT) ,in order to provide references for clinical treatment .Methods Totally 90 cases of patients with malignant glioma in our hospital from January 2011 to January 2013 were selected ,among them ,64 cases of MGMT negative expressing patients were divided into group A and group B with 32 cases in each group ,and 26 cases of MGMT positive expressing patients were enrolled into the group C . Group A was treated with combination of radiotherapy ,teniposide and nimustine ,group B was treated with radiotherapy‐temozolo‐mide combination regimen ,group C was treated with combination of radiotherapy ,teniposide and nimustine .The untoward reactions of the three groups were compared ,and the survival rate was observed after one year follow‐up .Results The hemoglobin ,leuko‐cyte ,granulocyte ,platelet ,bleeding ,alanine aminotransferase ,creatinine ,urea nitrogen ,peripheral neuritis ,untoward reactions a‐mong the three groups had no statistically significant differences (P>0 .05);the incidence rates of nausea and vomiting ,diarrhea , constipation among the three groups had statistically significant differences(P<0 .05) ,in which group C was significantly higher than that of group A and group B(P<0 .05) .Only one case in the group C was lost in the one year follow‐up .The median survival time was 10 months in group A and group B ,and was 7 months in group C .The median survival time in group C was significantly lower when compared with that in group A and group B(χ2 =7 .673 ,P=0 .006 ;χ2 =6 .395 ,P=0 .011) ,while there was no signifi‐cant difference of median survival time between group A and group B(χ2 =0 .063 .P=0 .802) .Conclusion The long‐term prognosis of patients with negative MGMT expression might be significantly worse than that of patients with negative MGMT expression in glioma .

Objective To investigate the therapeutic effects,adverse effects,and patterns of failure of elective irradiation of lymphatic drainage area (extended-field) and involved-field irradiation in three-dimensional radiotherapy (3DRT) in patients with esophageal cancer via a Meta-analysis.Methods The databases Wanfang Data,CNKI,VIP,CBM,PubMed,Embase,and Cochrane Library were searched to collect the controlled clinical trials on extended-field irradiation and involved-field irradiation in 3DRT in patients with esophageal cancer.Stata 11.0 was used for data analysis.The odds ratio (OR) with 95％ confidence interval was used to describe the differences between two groups.Results According to the inclusion and exclusion criteria,a total of 12 controlled clinical trials involving 1 095 patients with esophageal cancer were included in this meta-analysis.The results of the meta-analysis showed that compared with the involved-field irradiation group,the extended-field irradiation group had a significantly reduced rate of out-field failure in patients with esophageal cancer who received 3DRT (OR=3.727,P=0.007),but showed significantly higher rates of grade ≥ 3 acute radiation pneumonitis and radiation esophagitis (acute radiation pneumonitis:OR =0.348,P =0.001;radiation esophagitis:OR =0.385,P =0.000).The two groups had similar 1-,2-,and 3-year local control rate and overall survival rate (local control rate:OR=0.966/0.946/0.732,P=0.837/0.781/0.098;overall survival rate:OR=0.952/1.149/0.768,P=0.756/0.422/0.120),as well as a similar distant metastasis rate (OR=0.986,P=0.937).Conclusions Compared with involved-field irradiation,extended-field irradiation can reduce the rate of out-field failure in patients with esophageal cancer who receive 3DRT.However,it does not have significant advantages in local control rate and overall survival rate and has an increased incidence rate of adverse effects.

Objective To investigate the survival , recurrence patterns and risk factors in patients with stage ⅢA-N2NSCLC treated with curative surgery and adjuvant chemotherapy and to explore the significance of postoperative radiation therapy .Mte hods The clinical data of 290 patients with pathologically diagnosed stage ⅢA-N2 NSCLC after curative resection and adjuvant chemotherapy from January 2010 to December 2014 at our department were retrospectively analyzed .The survival and recurrence patterns were observed , and the factors affecting locoregional recurrence were analyzed .Results The median survival time was 31.5 months.The 1-,3 -and 5-year survival rates were 88.3%, 46.0%and 33.2%, respectively.The median locoregional control time was 38.5 months.The 1-, 3-and 5-year locoregional control rates were 78.6%, 55.2%and 41.0%, respectively.The median distant metastasis-free survival was 26.8 months.The 1-, 3-and 5-year distant metastasis-free survival rates were 76.4%, 45.5%and 39.5%, respectively.The median progression-free survival was 19.1 months.The 1-,3-and 5-year progression-free survival rates were 64.1%, 32.5%and 23.8%, respectively .Univariate analysis showed that clinical N status, histological type, pathological T stage, operation mode, the number of positive N2 lymph nodes and the number of positive N 2 lymph node stations had a significant influence on overall survival; clinical N status, histological type, the number of positive N2 lymph nodes and the number of positive N 2 lymph node stations had a significant influence on locoregional control .Multivariate analysis demonstrated that the number of N2 positive lymph nodes( P=0.017) was an independent factor for overall survival of stage ⅢA-N2 patients;the number of N2 positive lymph nodes (P=0.009) and histological type (P=0.005) were independent factors for locoregional recurrence .For left-sided lung cancer , the lymph node station failure sites were mostly in 2R, 4R, 5, 6 and 7, and the contralateral mediastinum was frequently involved .For rights-ided lung cancer , the lymph node station failure sites were mostly in 2R, 4R,7 , 10R and surgical stump.Conclusions Clinical N2, squamous cell carcinoma , positive N2 nodes of more than 3 and multiple positive N2 stations are poor prognostic factors for locoregional recurrence .Locoregional recurrence of left lung cancer frequently involves the contralateral mediastinum , while that of the right lung cancer usually locates in the ipsilateral mediastinum .