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 effect of Zhikepipa Mixture on the treatment of COVID-19 through network pharmacology analysis and molecular docking technology. 【Methods】 First, we performed the network pharmacology method to screen active compounds and targets so as to explore the mixture’s potential mechanisms in the treatment of COVID-19. In line with ADME screening index, like oral bioavailability (OB) ≥30% or drug likeness index (DL) ≥0.18, the active compounds against COVID-19 related targets were selected to construct the 'herb-compound-target’ network. Mechanism prediction of Zhikepipa mixture in the treatment of COVID-19 was analyzed by the interaction of the target sites, the bioinformatic annotation, and the metabolic pathway. Then, we used a molecular docking model to evaluate the binding ability between active compounds and 2019-nCoV (SARS-CoV-2) 3-chymotrypsin-like cysteine protease (3CL^pro) receptor-binding domain (PBD ID 6LU7), which was involved in mediating viral replication and transcription functions. 【Results】 The'herb-compound-target’ network showed 34 key compounds and 30 disease targets after overlapping with disease targets. The network topology analysis showed that those selected compounds with higher degree would produce marked anti-inflammatory effects by regulating 30 targets like PTGS1, IL1B, IL6, IL10, CXCL8 and JUN. AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway were involved in regulating hepatitis B and diabetic complications. In addition, Folium eriobotryae and Radix stemonae played important roles in the network. The molecular docking results showed that nine compounds were identified with higher docking score rank against 2019-nCoV 3CL^pro protease, and most of them were attributed to flavonoids. 【Conclusion】 Zhikepipa Mixture could exhibit both anti-inflammatory and anti-virus actions through multi-component, multi-target, and multi-pathway.

Objective:To explore the clinical features and possible pathogenesis of spontaneous remission of acute myeloid leukemia (AML) .Methods:We retrospectively analyzed the clinical data of a patient with spontaneous remission of AML, MLL-AF9 rearrangement, and abnormal liver function in the First Affiliated Hospital of Zhengzhou University, and the relevant pieces of literature were summarized.Results:The patient experienced lung infection, fever, and liver dysfunction and was treated with anti-infection and blood transfusion. After complete response (CR) , the patient remained in CR with mild, indirect bilirubin elevation at 35 months of follow-up. Additionally, 56 cases of adult AML (non-acute promyelocytic leukemia) were reported in the literature from 1990 to June 2021. The cases were checked by bone marrow aspiration, and our patients were summarized and analyzed. Furthermore, 57 patients, including 37 males and 20 females, with a median age of 51 (20-83) years and a median remission time of five months; 52 patients achieved complete remission. In addition, there were five cases with long-term remission and a chromosomal record, with no recurrence so far, three with normal karyotype and two with t (9;11) (q21;q23) .Conclusion:The spontaneous remission of leukemia is rare and may be related to immunosuppression and genes.

Objective: To explore the clinical and laboratory characteristics and therapeutic effect of acute promyelocytic leukemia (APL) with t(2;17;15). Methods: The G-banding technique was used for karyotypic analysis in a female patient with APL who was admitted to the First Affiliated Hospital of Zhengzhou University in December 2018. PML-RARα fusion gene was quickly detected by fluorescence in situ hybridization (FISH). The real-time quantitative polymerase chain reaction (RT-PCR) was used to detection 43 kinds of fusion gene, and the gene mutations were detected by next generation sequencing (NGS). The induction therapy was given with oral retinoic acid+ intravenous infusion of arsenic trioxide, followed by 3 courses of retinoic acid+ arsenic trioxide consolidation therapy. Results: The G-banding karyotypic analysis demonstrated 46, XX, t(2;17;15) (q31;q21;q22)[8]/46, XX[2]. FISH results indicated that 62.0% of analyzed cells were positive for the PML-RARα fusion gene. RT-PCR further revealed the positive PML-RARα fusion gene transcript. NGS detection of gene mutations showed no obvious abnormalities. After 39 days of induction therapy with retinoic acid and arsenic trioxide, the patient achieved complete remission (CR). The karyotype was 46XX[20], and PML-RARα/ABL was 0/100. Then, the patient was treated with 3 courses of consolidation therapy, and the results remained in CR. Conclusions APL with complex t(2;17;15) (q31;q21;q22) is rare, and the morphological characteristics are not typical, but it is still associated with the formation of PML-RARα fusion gene. Retinoic acid+ arsenic trioxide has a good therapeutic effect, and the long-term efficacy still needs follow-up.

Objective    To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods     Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results     CTC count of the malignant group was significantly higher than that of the benign group  (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/ml vs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion     The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.

Objective    To explore the diagnostic value of circulating tumor cells (CTC) measured by magnetic nanoparticle method in lung cancer. Methods    (1) We measured binding capability of A549 or NCI-H1965 cell lines with recognition peptide and capture efficiency by adding tumor cells into the whole blood of healthy human. (2) We measured CTC of 34 patients suspected with lung cancer, and the counting results of CTC were compared with the following pathological results. Results    (1) The binding capability was 80.0%±6.0% for A549 and 70.1%±4.8% for H1957, while the capture efficiency was 57.3%±7.0% for A549 and 37.3%±6.1% for H1975. (2) CTCs were identified in 71.9% of patients with lung cancer. The specificity was 83.3%, and area under receiver operating characteristic (ROC) curve was 0.792 (P=0.003). Conclusion    CTC measured by magnetic nanoparticle method has promising application in the diagnosis of lung cancer.

Amphiregulin is the ligand of epidermal growth factor receptor.It's widely expressed in many tissues and is involved in the oncogenesis,progression and metastasis of tumors.In the clinical study of lung caner,amphiregulin is a prognostic marker for NSCLC patients.Furthermore,amphiregulin is closely associated with the sensitivity and resistance of EGFRTKI treatment.Medicine target on amphiregulin can inhibit the activity of tumors.

Objective To study the changes of serum interleukin-8 (IL-8) and interleukin-10 (IL-10) in preterm infants delivered from mothers with chorioamnionitis (CA) and the possible effects on bronchopuhmonary dysplasia (BPD) and brain injury of preterm infants.Method From October 2014 to October 2015,clinical data from mothers without clinical manifestations of CA giving birth to a preterm baby (gestational age:26 to 33 weeks) were collected in Changzhou Maternal and Child Health Hospital and Suzhou Municipal Hospital.The infants were assigned to CA group and non-CA group according to their mother's placenta pathology.The levels of serum IL-8 and IL-10 were measured using enzyme-linked immunosorbent assay (ELISA) on day 1 and day 7,while the levels of WBC,CRP and PCT were measured at birth.The incidences of BPD and brain injury were also reviewed.Result A total of 67 preterm infants were included,with 51 in the CA group and 16 non-CA group.The levels of IL-8 were significantly higher in the CA group than the non-CA group on both day 1 and day 7 [(21.6 ±9.7) ng/L vs.(7.3 ±2.3) ng/L,(26.6 ± 12.9) ng/L vs.(7.3 ± 2.1) ng/L].The IL-10 levels were significantly lower on day 1 [(1.92±0.17) ng/Lvs.(2.04±0.18) ng/L] and higher on day 7 [(2.42±0.60) ng/L vs.(2.03 ±0.18) ng/L] in the CA group.Significant differences existed on the incidences of BPD (54.9％ vs.25.0％) and brain injury (74.5％ vs.43.8％) between the two groups (P ＜ 0.05).The levels of CRP and PCT were higher in CA group (P ＜ 0.05) and the WBC was similar between the two groups (P ＞ 0.05).In CA group,on both day 1 and day 7,infants with BPD had similar IL-8 and IL-10 levels comparing with infants without BPD(P ＞ 0.05),also were infants with brain injury comparing with infants without brain injury.Conclusion Chorioamnionitis in pregnant women may affect serum cytokines levels in premature infants and lead to high incidences of BPD and brain injury.

Objective To evaluate the different arteriographic manifestations of acute renal arterial hemorrhage,and the treatment effects of emergency interventional embolization.Methods 87 patients with renal arterial hemorrhage who were failed to conservative treatment underwent the renal arteriography to confirm the position and degree of lesion.According to the arteriographic manifesta-tions,appropriate embolic agents such as spring coil,acrylic acid microspheres and the like were used to embolize the targeted vessel. The arteriographic manifestations and embolization efficacy were retrospectively analyzed.Results Contrast medium leakage was showed by renal angiography in 43 patients,13 of whom had arterio-venous fistula (AVF)and 1 5 of whom had renal pseudoaneu-rysms (RAP).Among this 1 5 patients,there were 5 patients with arteriovenous fistula and one patiernt with artery-calyces fistula. Hemorrhage of tumor vessel was shown in 1 5 patients and renal arteriovenous malformation (RAVM)in 1.47 patients underwent renal artery CT arteriography before emergency interventional embolization.The hematuresis was completely stopped or significantly relieved in 82 of all patients.Only 3 patients with renal trauma and 2 patients with percutaneous nephroscope were still had haematu-ria.All patients were followed up for 2 years.The total effective rate of emergency interventional embolization treatment was 94.25%(82/87),and no serious complications were observed.Conclusion As a safe,effective and micro-invasive treatment,emergency in-terventional embolization therapy can be used to treat the acute renal hemorrhage effectively.It can keep the maximum renal func-tion.Though acute renal hemorrhage angiography may have different manifestations,the choice of embolic agents is the key to stop the symptom.Renal artery CTA before embolotherapy is important for the diagnosis and therapy of acute renal hemorrhage.

Objective To investigate the correlation of endothelial function variation with pulse pressure index in Uygur acute coronary syndrome patients in Xinjiang. Methods Uygur patients were divided into acute coronary syndrome group (n=208) and control group (n=157) according to their Coronary angiography results. Height, weight and blood pressure were measured on admission and basic medical history were recorded. Fasting blood glucose (FBG), three acyl glycerin (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were ex-amined using fasting venous blood;Plasma Coagulation FactorⅧ(CFⅧ) and von Willebrand factor(vWF)were examined using ELISA. Results There are no statistical difference in age, gender, history of hypertension, diabetes history, history of smoking, drinking, body mass index, PPI, HDL-C and FBG between two groups. The systolic pressure, diastolic blood pres-sure, pulse pressure, TG, TC, LDL-C and vWF, CFⅧlevels in acute coronary syndrome group were higher than those in the control group (all P<0.05). The levels of plasma vWF and CFⅧwere positively correlated with pulse pressure and PPI, it also was positively correlated between the levels of plasma vWF and CFⅧ(P<0.01). Conclusion The endothelial func-tion was significantly impaired in Xinjiang Uygur patients with acute coronary syndromes, and vascular endothelial damage was positively correlated with pulse pressure and PPI. The pulse pressure and PPI can be used to evaluate the vascular endo-thelial function indirectly.