Objective To investigate the active ingredients of Zizyphi Spinosae Semen(ZSS)in relieving benzodiazepine(BDZ)dependence and its molecular mechanism based on the integrated Traditional Chinese Medicine and chemical drugs idea of"enhancing effect and reducing toxicity"via the approach of network pharmacology and the technique of molecular dynamics simulation.Methods First,literature search was undertaken to find the main components of ZSS.Then,the major effective constituents of ZSS in relieving BDZ dependence and its target of action were explored on the basis of network pharmacology and molecular docking.Finally,the relationship between core components of ZSS and key proteins was further verified through the technique of molecular dynamics simulation.Results After literature search,a total of 24 chemical components in ZSS were found to act on 731 targets.Through establishing the network of"ingredients-targets-pathways",topology analysis was performed to obtain nine core components such as linoleic acid,palmitic acid,oleic acid,tetradecanoic acid,spinosin,oleanolic acid and jujuboside A,as well as five key targets including AR,PTGS2,PPARG,RXRA and CYP19A1.Bioinformation enrichment analysis was made to obtain critical pathways such as calcium signaling pathway,cAMP signaling pathway,IL-17 signaling pathway and TNF signaling pathway.The results of molecular docking revealed that there was a good combination between core components of ZSS and key targets,and it was mainly dominated by hydrogen bonding.Furthermore,the molecular dynamics simulation experiments indicated that the combinations between jujuboside A and RXRA,oleanolic acid and RXRA,spinosin and PPARG were stable,and these three active ingredients played an important role in improving BDZ dependence.Conclusion The active components in ZSS may exert multi-target and multi-pathway intervention effects on BDZ dependence by means of processes such as immunoregulation,anti-anxiety,and anti-insomnia.

Objective To explore the comparative application of phase and diaphragmatic navigation in three-dimensional magnetic resonance cholangiopancreatography(3D-MRCP)thin-layer scanning in elderly patients.Methods A total of 180 elderly patients were scanned by phase and diaphragmatic navigation via Siemens Aera1.5T superconducting MR scanner.The acquired images were reconstructed by 3D reconstruction.The anatomical structure,image quality and disease diagnosis were compared between the phase and diaphragmatic navigation groups.Results In liver of anatomy,the liver of primary bile duct,the superior,middle and inferior extrahepatic bile duct and the gallbladder could be well displayed,and the difference was not statistically significant between the two groups(P＞0.05).The display of pancreatic duct and the liver of secondary bile duct of diaphragmatic navigation was significantly better than those of phase navigation(P＜0.05).In terms of image quality,the excellent rate of diaphragmatic navigation was significantly higher than that of phase navigation,and the difference was statistically significant(P＜0.05).There were no statistically significant differences in the detection rate of pancreatobiliary system diseases,the diagnostic rate of cholelithiasis,common bile duct stones,common bile duct dilatation and pancreatic duct dilatation between the two groups(P＞0.05).Conclusion Diaphragmatic navigation is signifi-cantly better than phase navigation in the display of the anatomical structure of the pancreatic duct,the liver of secondary bile duct,and the excellent rate of image quality.Diaphragmatic navigation is more suitable for thin-layer 3D-MRCP scanning in elderly patients.

Objective:To evaluate the effects of opioid-sparing analgesia on the incidence of sepsis in severely burned patients in the retrospective cohort study.Methods:The clinical data from patients with severe burns admitted to three teaching hospitals in Guangdong from 2011 to 2020 were retrospectively extracted and analyzed. The patients were divided into 2 groups based on the analgesic regimen within 30 days after injury: continuous opioids analgesia group (continuous opioid infusion at a relative constant rate for more than 72 h) and opioid-sparing analgesia group (patient-controlled intravenous analgesia/intermittent administration/opioid-free analgesia). Patient′s age, severity of burn, inhalation injury and basal pain score at rest were matched by the propensity score at a 1∶1 ratio. The primary outcome measure was the occurrence of sepsis within 90 days of admission. Secondary outcome measures included 30-day and 90-day all-cause mortality, clinical diagnosis of multiple organ dysfunction syndrome, and prevalence of burn wound infection. The amount of opioid used was also recorded.Results:A total of 328 severely burned patients were finally enrolled, with 145 patients in continuous opioid analgesia group and 183 patients in opioid-sparing analgesia group, and 110 pairs of patients (220 cases) were finally matched by the propensity score.Compared with continuous opioid analgesia group, the total consumption of opioid, daily consumption per analgesia, and consumption per burn area were significantly decreased, and the incidence of sepsis and wound infection was decreased( P<0.05), and no significant change was found in the incidence of multiple organ dysfunction syndrome, 30-day and 90-day all-cause mortality in opioid-sparing analgesia group( P>0.05). Conclusions:Compared with the continuous opioid analgesia regimen, opioid-sparing analgesia can reduce the risk of sepsis in severely burned patients.

Objective To investigate the personal dose level of occupational external exposure among interventional radiology workers in Liaoning Province of China, and to provide a reference for better occupational radiation protection. Methods According to the national standard GBZ 128—2016 Specifications for individual monitoring of occupational external exposure, the thermoluminescence method was used to measure the monitoring dose inside the lead clothes (H_W) and outside the lead clothes (H_N) of interventional radiology workers, and the Mann-Whitney U test and the Kruskal-Wallis H test were used for statistical analysis. Results Dual dosimeter monitoring data were collected from 307 interventional radiology workers in Liaoning Province in 2019, with a mean annual effective dose of 0.81 mSv and a maximum annual effective dose of 7.03 mSv, and 72.96% of the workers monitored had an annual effective dose of less than 1 mSv. The interventional radiology workers in tertiary hospitals had a significantly higher mean annual effective dose than those in secondary hospitals (0.95 mSv vs 0.65 mSv, P < 0.05). There was a significant difference in mean annual effective dose between departments (P < 0.05), and the department of interventional radiology had a significantly higher mean annual effective dose than the other departments (0.92 mSv vs 0.64 mSv), while the department of cardiology had a similar mean annual effective dose to the cerebrovascular department (0.78 mSv vs 0.78 mSv). Conclusion The occupational exposure dose of 307 interventional radiology workers in Liaoning Province meets the requirements in national regulations and standards and is higher than the national level, which suggests that radiation protection supervision and personal training should be further strengthened for interventional radiology.

Objective:To investigate the prognostic significance of different IDH mutations and accompanying gene mutations in patients with non-M 3 acute myeloid leukemia (AML) . Methods:Second-generation sequencing was performed to detect the mutations of 22 genes in 389 patients with AML in the First Affiliated Hospital of Zhengzhou University from June 2016 to December 2018, and Kaplan-Meier and Cox regression models were used to analyze the prognostic factors.Results:The mutation frequency of IDH1 and IDH2 was 6.2% and 8.7% , respectively, in all patients without co-mutation. The IDH2 mutant group had an older age, higher proportion of bone marrow primitive cells, more common normal karyotype, and more common RUNX1 and SRSF2 mutations compared with IDH2 wild-type group. Univariate analysis of variance showed that the median OS and PFS of IDH1 mutation group were significantly shorter than those of the wild-type group ( P<0.05) . IDH2 mutation as a single variable and IDH2R140 mutation had no significant effect on the prognosis, while different mutation sites had different effects. Compared with the IDH2 wild-type group, the IDH2R172 mutation group had lower complete remission (CR) rate and shorter median OS and PFS ( P<0.05) . In patients with normal karyotypes or aged ≥50 years, IDH2 mutation as a single variable had no significant effect on the prognosis, IDH1 mutation and IDH2R172 mutation were associated with poor OS and PFS ( P<0.05) , and IDH2R140 mutation had no significant effect on OS and PFS. Approximately 74.1% (43/58) of patients with IDH mutation simultaneously carried other gene mutations; however, the number of accompanying gene mutations had no significant effect on the prognosis. Among 58 patients with IDH mutation, the CR rate of patients with NPM1 mutation was significantly higher than that of patients in the NPM1 wild-type group (81.8% vs 36.4% , P=0.014) , the median OS in patients with DNMT3A mutation was lower than that of patients with DNMT3A wild type [4.0 months (95% CI 3.8-4.2) vs 6.3 months (95% CI 2.4-10.2) , P=0.041) ]. Multivariate analysis showed that age ≥60 years and white blood cell count ≥100×10 9/L were independent risk factors for OS and PFS, while CR after two courses of treatment and hematopoietic stem cell transplantation were independent prognostic favorable factors for OS and PFS. Conclusion:In patients with AML (non-M 3) , IDH gene mutations often coexisted with other gene mutations, and different subtypes and accompanying gene mutations of IDH have different prognostic significance.

Objective To investigate the efficacy and safety of domestic bortezomibˉbased chemotherapy for patients with multiple myeloma (MM). Methods The clinical data of 60 MM patients treated with domestic bortezomibˉbased chemotherapy regimen (the observation group) in the First Affiliated Hospital of Zhengzhou University from April 2018 to October 2018 were retrospectively analyzed, which were compared with 112 MM patients treated with original treatment regimen (the control group) at the same hospital from November 2010 to November 2014. According to the disease stage, the patients were divided into newly diagnosed MM (NDMM) group and relapsed refractory MM (RRMM) group, and efficacy and adverse reactions of domestic bortezomib were evaluated. Results The total response rate (ORR) of the observation group was 71.7% (43/60), severe complete response (sCR) + complete response (CR) rate was 16.7% (10/60), very good partial response (VGPR) rate was 18.3% (11/60), and partial response (PR) rate was 36.7% (22/60). The ORR of NDMM group (45 cases) and RRMM group (15 cases) was 82.2% (37/45) and 40.0% (6/15), respectively, and the difference was statistically significant (χ2＝ 9.877, P < 0.05). There was no significant difference between ISS stage Ⅰ+Ⅱ and stage Ⅲ [ORR: 75.7% (28/37) vs. 65.2% (15/23), respectively; χ2＝0.764, P >0.05]. ORR and CR rates in the NDMM group and RRMM group of the observation group and the control group were not statistically different (all P>0.05). In the treatment of bortezomibˉbased chemotherapy, the common adverse reaction was peripheral neuropathy, mostly belonging to grade 1-2. Other side effects included hematocytopenia, gastrointestinal events and herpes zoster, which could be alleviated or restored to normality after supportive treatments. One patient died of pulmonary infection, respiratory failure and septic shock during the intermittent period of chemotherapy. Conclusion ORR of domestic bortezomibˉbased chemotherapy in treatment of the patients with MM is high, and the incidence of adverse reactions shows no significant increase compared with original drugs.

Objective: To investigate the clinical characteristics and prognostic factors in elderly patients with acute myeloid leukemia(AML). Methods: Clinical data of 232 patients with acute myelocytic leukemia(AML, except for acute promyelocytic leukemia) admitted in our hospital from January 2012 to December 2015 were retrospectively analyzed.Factors affecting complete remission(CR) were analyzed by using χ² test, and Kaplan-Meier survival analysis was conducted.Univariate and multivariate analysis of prognostic factors were performed by using Log-Rank test and Cox regression model respectively. Results: Of 232 patients, 195 patients received induction chemotherapy, among whom 8 patients died in early phase, efficacy could not be evaluated in 25 cases, with 162 patients for final statistical study.The CR rate was 37.0%(60/162) after the first therapy course, and overall CR rate was 54.9%(89/162). Thirty-seven patients received palliative treatment, among whom 6 patients died in early phase and none achieved CR.Therefore, the 162 patients receiving an induction chemotherapy, whose efficacy can be evaluated, could be clinically analyzed.They were in 60-69 years old(χ²=4.102, P=0.043), with ECOG score≤2(χ²=9.917, P=0.002), NPM1⁺ FLT3-ITD^-(χ²=6.423, P=0.038), favorable karyotypes(χ²=6.033, P=0.049), and related to a higher CR rate.The median overall survival(OS) was 205 days in the 232 patients.Univariate analysis results demonstrated that age(χ²=8.700, P=0.003), white blood cell(WBC) count≥100×10⁹/L(χ²=4.249, P=0.039), karyotypes(χ²=4.807, P=0.028), palliative treatment(χ²=191.221, P=0.000) were influencing factors for the prognosis.Multivariable analysis showed that age(HR=0.464, 95%CI: 0.245-0.877, P=0.018), karyotypes(HR=3.618, 95%CI: 1.491-6.728, P=0.003) and whether or not to receive induction chemotherapy(HR=0.076, 95%CI: 0.030-0.194, P=0.000) were independent influencing factors for OS in elderly patients with AML. Conclusions The prognosis of elderly patients with AML is affected by multiple factors.Age, karyotypes and whether or not to receive induction chemotherapy are independent influencing factors for OS in elderly patients with AML.

Objective To analyze the clinical features and prognosis of CD34-positive and CD34-negative adult patients with acute T-lymphoblastic leukemia (T-ALL),and to explore the value of CD34 expression for prognosis of patients with T-ALL.Methods 75 adult patients diagnosed with T-ALL from January 2012 to July 2015 in the Department of Hematology,the First Affiliated Hospital of Zhengzhou University,were analyzed retrospectively.According to the expression of CD34,the patients were divided into CD34-positive group and CD34-negative group,and then the clinical characteristics and prognosis of both groups were analyzed.Results In 75 patients,CD34-positive group had 24 (32.0 ％) patients and CD34-negative group had 51 (68.0 ％) patients.Between the two groups,there was no significant difference in these factors,such as sex,age,infiltration of liver,spleen and lymph nodes,thrombocytopenia,high white blood cell count,abnormal karyotype,complete remission within 4 weeks and central nervous system leukemia (CNSL).The proportions of patients with hemoglobin (Hb) ＜ 90 g/L and expression of myeloid lineage marker were higher in the CD34-positive group than those in the CD34-negative group (x2 =5.888,P=0.015;x2 =10.758,P =0.001,respectively).There were only 18 patients treated with hematopoietic stem cell transplantation (HSCT),57 patients were not.In patients without HSCT,the median survival time in the CD34-positive group and CD34-negative group was significant different (5 months vs.32 months,x2 =9.172,P =0.002).Conclusions CD34 expression in adult patients with T-ALL appears to be associated with Hb ＜ 90 g/L and the expression of myeloid lineage markers.For the patients without HSCT,CD34 is likely negatively related with the prognosis.

Objective To investigate the effect of postremission consolidation therapy with intermedium-dose cytarabine (MDAC) in elderly patients with acute myelogenous leukemia (AML). Methods Clinical data of 61 elderly AML patients (except M3) in postremission who achieved complete remission (CR) in two period of remission induction program were retrospectively analyzed. Results There were 26 cases in MDAC group and 35 cases in standard-dose cytarabine (SDAC) group. In MDAC group and SDAC group, the relapse free survival (RFS) time were 42.7 months and 16.0 months respectively (P= 0.002), the overall survival (OS) time were 44.6 months and 18.2 months respectively (P= 0.004), and the cumulative relapse frequencies rates were 26.9 % (7/26) and 54.3 % (19/35) respectively (x 2= 4.567, P= 0.033). However, 3 years OS rate of the two groups were 23.1%(6/26) and 8.6%(3/35) (x 2=2.496, P=0.114) , and there was no significant difference in the incidence of adverse reactions between the two groups (all P > 0.05). Conclusion MDAC could improve RFS and OS for the elderly AML patients in postremission who received CR in the early stage, and the incidence of adverse reactions is similar to that of SDAC.

Objective To evaluate the application of multi-parameter three-dimension arterial spin labeling (3D-ASL) in observing the brain perfusion of patients with transient ischemic attack (TIA). Methods A total of 42 TIA patients, admitted to our hospital from July 2014 to March 2017, were included in this study. All subjects underwent conventional MRI, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA) and 3D-ASL scanning. Abnormal signals, and cerebral arterial stenosis or occlusion were observed under MRI, DWI and MRA; cerebral blood flow (CBF) map was drew after analyzing the 3D-ASL imaging, and abnormal reperfusion of ASL-CBF was qualitatively and quantitatively analyzed. The detection rate of abnormal reperfusion in TIA patients by 3D-ASL (PLD=1.5 s, PLD=2.5 s) and MRA were compared. Results Forty-two TIA patients showed no positive findings on conventional MRI and DWI maps, of which 18 patients showed different degrees of cerebral artery stenosis on MRA maps. Twenty-seven patients (PLD=1.5 s, 64.29％) and 21 (PLD=2.5 s, 50％) on ASL-CBF maps showed different sizes and degrees of abnormal hypoperfusion, and significant difference was found in detection rate of hypoperfusion by 3D-ASL (PLD=1.5 s and PLD=2.5 s, χ2=23.333, P=0.000). The detection rates of hypoperfusion by 3D-ASL (PLD=1.5 s and PLD=2.5 s) were 中华神经医学杂志2017年12月第16卷 第12期 Chin J Neuromed, December 2017, Vol.16, No.12 significantly higher than that by MRA (χ2=17.500, P=0.000; χ2=31.500, P=0.000). Conclusions The 3D-ASL can quantitatively analyze the degrees of perfusion of patients with TIA. 3D-ASL can comprehensively reflect the perfusion status in patients with TIA, and short PLD 3D-ASL is more sensitive than long PLD ASL in finding TIA, while long PLD 3D-ASL can reflect the perfusion status more truly.