Objective To use network pharmacology to mine and predict the targets and related signaling pathways of Miaoyao Yiai Tang(Miao-Yi-Ai-Tang,MYAT)in the treatment of small cell lung cancer(SCLC).And animal experiments to verify its mechanism of action,to provide a theoretical basis for basic experiments and clinical applications.Methods The active ingredients of MYAT were obtained from the TCMSP database,combined with PubMed data,Swiss Target Prediction database and Uniprot database to obtain potential targets;SCLC-related genes were collected through the DrugBank database,Genecards database,OMIM database and TTD database,and the Venny 2.1 platform After obtaining the intersection genes of MYAT and SCLC,import them into the STRING database,construct a protein-protein interaction(PPI)network,use Cytoscape 3.9.1 software for visual analysis,and use Metascape database for GO enrichment analysis and KEGG pathway analysis,to predict the direct action target and signaling pathway of MYAT in the treatment of SCLC.Using AutoDock Tools 1.5.7 software for molecular docking to verify the close relationship between the two.For cytological experiment verification,the cultured cells were treated with MYAT and the expression of β-catenin,AXIN,c-myc was detected by qPCR,and the expression of β-catenin in the cells was detected by Western blot;animal experiments were established to establish a subcutaneous xenograft tumor model of lung cancer NCI-H446,to observe the effect of MYAT on tumor growth.Results A total of 65 effective components of MYAT,1368 SCLC genes,and 260 MYAT-SCLC intersection genes were obtained.Enrichment analysis showed that they were related to cancer pathways,PD-L1/PD-1 pathways,NF-κB pathways,Wnt and other signaling pathways.The results of molecular docking validation showed that the binding energies of active components and core target proteins were all<0 kJ·mol-1,which indicated that the protein could spontaneously bind to active components and be stable.Cell experiments showed that the expression levels of β-catenin,c-myc and AXIN mRNA were significantly down-regulated in the MYAT group(P<0.05).Animal experiments show that:MYAT can significantly inhibit the growth of tumors in vivo.Conclusion Miao-Yi-Ai-Tang can inhibit the proliferation of small cell lung cancer through Wnt/β-catenin signaling pathway.

Objective:To analyze and summarize the epidemiological and molecular characteristics of SARS-CoV-2 Delta variant, a variant of concern (VOC), in Henan Province in 2021 in order to provide a basis for epidemic prevention and control.Methods:According to the feedback of sequencing results from Chinese Center for Disease Control and Prevention, 111 patients infected with SARS-CoV-2 Delta VOC were selected from the Henan imported and local cases in 2021. Basic patient information was obtained from the pandemic website. The differences in age, gender, vaccination history, the number of vaccine doses and different clinical types were analyzed. Moreover, the differences in RT-qPCR results of ORF1 ab gene and N gene Ct values between cases of different genders and symptoms were analyzed statistically. Sequencing results of the nucleotide and S protein mutation sites were analyzed. Results:There was no significant difference in the gender distribution of 111 cases between different age groups (χ 2=2.217, P=0.529). There was also no significant difference in clinical types between patients with different vaccination history (χ 2=12.074, P=0.209). The Ct values of most SARS-CoV-2 nucleic acid-positive specimens were distributed in the lower range and the viral loads were higher. The difference in the Ct value of ORF1 ab gene between different gender groups was not statistically significant (χ 2=1.646, P=0.439), but were significantly different among asymptomatic, mild, normal, and severe cases (χ 2=13.257, P=0.039). There was no significant difference in N gene Ct value among cases of different genders or different symptoms (all P>0.05). The 111 patients in this study were mainly found through close-contact screening and full-staff nucleic acid screening and accounted for 62.2% (69 cases) of the total. The sequencing length coverage was basically greater than 99% (accounting for 90.1%, 100/111); the total number of nucleotide mutation sites was mostly in the range of 46-50 (86.4%, 89/103); the total number of S protein mutation sites was mostly 12 (82.5%, 85/103). The 103 Delta mutants all contained nine mutation sites, which were T19R, R158G, L452R, T478K, D614G, P681R, D950N, E156del and F157del, with a mutation rate of 100%. Conclusions:People were highly susceptible to the SARS-CoV-2 Delta in Henan Province in 2021. High viral load and increase in the ORF1 ab gene load would aggravate the clinical symptoms.

Objective:To investigate the level and changing trend of microparticles (MPs) in super-elderly infected patients, and explore its early warning effect on infection.Methods:The infected patients ≥ 85 years old admitted to the Second Medical Center of Chinese PLA General Hospital from December 2018 to March 2019 were selected as the observation group, and the healthy volunteers ≥ 85 years old in the same period were selected as the control group. Venous blood samples were collected at the 2nd hour, the 2nd day and the 7th day after fever, and the inflammatory markers such as white blood cell count (WBC), neutrophil percentage (NEUT), C-reactive protein (CRP) and procalcitonin (PCT) were measured. The levels of MPs were determined by flow cytometry. AnnexinⅤlabeled CD11b positive MPs (AnnexinⅤ +/CD11b + MPs) represented leukocyte microparticles (LMPs), and AnnexinⅤlabeled CD66b positive MPs (AnnexinⅤ +/CD66b + MPs) represented neutrophil microparticle (NMPs). The differences of each index at different time points between the two groups were compared, and the predictive value of each index to the infection of elderly patients was analyzed by receiver operating characteristic (ROC) curve. Results:A total of 38 subjects were enrolled, including 28 cases in the observation group and 10 cases in the control group. The levels of LMPs and NMPs in the observation group increased to the peak at the 2nd hour after fever, and were significantly higher than those in the control group [LMPs (cells/μL): 55.0 (28.8, 197.2) vs. 19.0 (13.5, 28.3), NMPs (cells/μL): 226.5 (123.3, 516.5) vs. 26.5 (22.0, 48.8), both P < 0.01]. With the control of the disease, LMPs and NMPs decreased gradually. The NMPs on the 2nd day was significantly lower than that at the 2nd hour of fever [cells/μL: 106.0 (40.0, 309.0) vs. 226.5 (123.3, 516.5), P < 0.05], and the LMPs and NMPs on the 7th day were significantly lower than those on the 2nd day [LMPs (cells/μL): 17.0 (12.5, 43.8) vs. 42.0 (13.0, 117.0), NMPs (cells/μL): 30.0 (15.8, 62.0) vs. 106.0 (40.0, 309.0), both P < 0.05]. There was no significant difference in the levels of LMPs and NMPs between the two groups on the 7th day. Among the inflammatory markers, the NEUT in the observation group was significantly higher than that in the control group at the 2nd hour of fever (0.70±0.09 vs. 0.59±0.04, P < 0.01), but there was no significant difference in WBC, CRP and PCT between the two groups. On the 2nd day, the inflammatory markers in the observation group reached the peak and were significantly higher than those in the control group [WBC (×10 9/L): 9.33±2.44 vs. 6.37±1.28, NEUT: 0.78±0.08 vs. 0.57±0.04, CRP (mg/L): 5.67±2.99 vs. 0.33±0.18, PCT (μg/L): 0.80±0.67 vs. 0.07±0.03, all P < 0.01]. On the 7th day, the inflammatory markers in the observation group decreased significantly, and there was no significant difference between the observation group and the control group. ROC curve analysis showed that the area under ROC curve (AUC) and 95% confidence interval (95% CI) of LMPs and NMPs on the day of fever were higher than those of WBC, NEUT, CRP and PCT [0.888 (0.763-1.000), 0.973 (0.931-1.000) vs. 0.679 (0.346-0.811), 0.829 (0.700-0.958), 0.607 (0.404-0.811), 0.554 (0.358-0.749)]. Conclusion:LMPs and NMPs are significantly increased in the early stage of fever, which can predict the incidence of infection in the super-elderly patients.

Objective To investigate the effect of first aid nursing path under the center of chest pain on the diagnosis and treatment of patients with ST-segment elevation myocardial infarction (STEMI). Methods A total of 79 cases of STEMI patients who had been selected for emergency treatment after the establishment of the chest pain center were as the experimental group. The patient's first aid nursing path was used in the center of chest pain. A total of 159 cases of STEMI patients before the establishment of the chest pain center were as the control group, Application of traditional clinical pathway. Compared to the diagnosis and treatment effect of two groups of patients. Results The rate of completed the project within 10 min for the experimental group: the completion of electrocardiogram examination (91.1% vs 84.9% ), oral aspirin, clopidogrel, or lindinda (81.0% vs 75.5%), and laboratory medical order (79.7% vs 69.8%) were higher than those in the control group, and the difference was statistically significant (χ2=2.31, 1.68, 2.06, P < 0.05). The day of hospitalization in the experimental group was less than that of the control group (6.48±3.82 vs 9.76± 4.32), and the difference was statistically significant (t=-9.80, P < 0.05). The mortality rate during hospitalization was lower than that of the control group (5.66% vs 3.8% ), and the difference was statistically significant (χ2=-2.24, P<0.05). Conclusion The first aid nursing path in the center of chest pain can shorten the time of diagnosis and treatment of STEMI patients and improve the diagnosis and treatment effect of STEMI patients.

Objective To investigate the clinical effects of the treatment of cancer pain control by the partic-ipation of pharmacist,and the effect on cancer patients and families mental state and quality of life.Methods Clini-cal pharmacists took participate in the standardized treatment of pain,before and after different intervention,NRS scale was used to assess the patients'pain,self -rating anxiety scale(SAS)and self -rating depression scale(SDS)were used to assess the patients and families'psychological mental status.SF -36 scale was used to assess the quality of life.Results Compared with pre -intervention,two weeks later,the overall situation of patients with pain was signifi-cantly improved[NRS score (4.72 ±1.13)points vs.(3.57 ±0.97)points,t =7.722,P <0.01].Patients and their families,anxiety and depression significantly alleviated [patients:SAS (32.56 ±4.66 )points vs.(60.31 ± 4.27)points,t =38.180,P <0.01,SDS (45.89 ±5.46)points vs.(68.34 ±6.23)points,t =28.250,P <0.01;families:SAS(33.76 ±4.82)points vs.(50.31 ±6.47)points,t =15.593,P <0.01,SDS (32.89 ±3.54)points vs. (52.34 ±6.23)points,t =15.593,P <0.01 ].At the same time,the patients and families'quality of life were improved.Conclusion Clinical pharmaceutical care can relieve the body pain,meanwhile,those could effectively relieve the anxiety,depression and other negative psychology of cancer patients and families,improve the whole quality of life.

AIM:To detect the changes of active status of bypass signaling pathways in EML4-ALK positive lung cancer cell line H3122 treated with alectinib, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), and to explore the potential mechanisms.METHODS:EML4-ALK positive cell line H3122 was treated with increasing concentrations of alectinib or/and induced by HGF, EGF and TGF-α.The cell viability was measured by CCK-8 assay.The cell apoptosis was analyzed by flow cytometry.The protein levels and phosphorylation status of ALK, c-Met and EGFR, and the downstream molecules AKT, ERK, p-AKT and p-ERK were examined by Western blot.RESULTS:The viability of the H3122 cells was inhibited by alectinib in a dose-dependent manner after administrated for 72 h, and the IC50 value was 0.042 μmol/L.The concentration-growth curves of the H3122 cells shifted to the right after induced by HGF, EGF and TGF-α.After treatment with alectinib at 0.05 μmol/L for 48 h, the apoptotic rate of H3122 cells was (20.12±1.36)%, while the apoptotic rates of the cells in the groups of alectinib combined with HGF, EGF or TGF-α were (7.85±1.03)%, (5.60±0.79)% and (4.58±1.00)%, respectively.Those values were remarkably lower than those in alectinib single treatment group (P<0.05).Alectinib inhibited the protein levels of p-ALK and its downstream signaling pathway molecules, while HGF significantly up-regulated the protein levels of p-Met and its downstream p-AKT and p-ERK.Besides, EGF and TGF-α remarkablely up-regulated the protein levels of p-EGFR and its downstream p-AKT and p-ERK.Combined treatment with crizotinib and 17-DMAG successfully inhibited the viability of the H3122 cells even in the presence of the HGF and EGFR ligands, respectively.CONCLUSION:Bypass signaling pathways are activated by HGF, EGF and TGF-α in EML4-ALK positive lung cancer cell line H3122, which may be linked to alectinib resistance.

AIM: To investigate the role of HGF/c-Met signaling pathway in crizotinib-induced apoptosis of different lung carcinoma cell lines and to analyze its potential regulatory mechanisms .METHODS: EML4-ALK positive cell line H2228, c-Met proliferation cell line H1993 and control cell line A549 were treated with crizotinib at different doses for different time periods .The viability of the cell lines was measured by MTT assay .The apoptosis was analyzed by flow cytometry with PI staining.The protein levels of MET and phosphorylated MET (p-MET) of HGF/c-Met signaling pathway as well as its down-stream key proteins AKT , ERK, p-AKT and p-ERK in the cell lines before and after crizotinib treatment were examined by Western blot .RESULTS:The growth of H1993, H2228 and A549 cell lines was inhibited after crizoti-nib treatment for 72 h in a dose-dependent manner .Apoptotic rates of H1993 cells and H2228 cells were increased with the crizotinib concentration and exposure time .Down-regulation of p-MET, p-AKT and p-ERK at protein levels in H1993 cells and H2228 cells after exposure to crizotinib for 72 h was confirmed by Western blot .No obvious change of the related-pro-teins of HGF/c-Met signaling pathway was found in A 549 cell line.CONCLUSION: HGF/c-Met signaling pathway may contribute to crizotinib-induced apoptosis of H1993 cells and H2228 cells, which provides the experimental basis for MET-targeting treatment of lung cancer .

Objective To investigate and analyze the application of three steps therapy analgesics in good pain management(GPM)-ward,in order to provide rational analgesics drug application in clinical practice.Methods Through the hospital HIS system,the application data of analgesics in GPM-ward from Jan.2014 to Dec.2015 were collected and analyzed.Results The sum and proportion of the strong opioid drug was lined first.The total DDDs of the three -stage analgesics ranked from high to low was celecoxib >tramadol >oxycontin >morphine >fentanyl trans-dermal.The celecoxib was usually assisted the other;in addition,tramadol's DDDs and expense amount decreased, which was in the line with NCCN guidelines.Moreover,oxycontin's DDDs and expense amount increased.As well as, anesthesia prescription qualified rate was 93.5%,medical record standard rate was 80.5% in 2014,prescription qual-ified rate was rose to 97.5%,medical record standard rate was rose to 91.5% in 2015.Conclusion The application of cancer pain drug was basically rational in GPM-ward,which is in line with the principles of cancer pain relief by the mouth,by the clock,by the ladder and for the individual.

Objective To compare the difference of impact on the cellular immunity between laparoscopic and transabdominal radical hysterectomy. Methods 60 patients with early cervical cancer (Ⅰa2~Ⅱa1), half of them were assigned to do abdominal radical hysterectomy (ARH) and the other half for laparoscopic radical hysterectomy (LRH). Adopt flow cytometry (FCM) detect peripheral blood T lymphocyte subsets, NK cells, CIK cells and T lymphocyte ac-tivation function on one day before surgery, one day, five days, and 28 days after the surgery separately. Compare the changes of immune status. Results After one day, the number of T lymphocyte subsets declined compared with preoperative one day(P <0.05). After five days, each index in LRH group was increased compared with postoperative one day, and the degree of decline is less than the ARH group ( P< 0.05), and recovered faster. After one day, the number of HLA-DR+CD3+in LRH group compared with the preoperative one day declined and HLA-DR+CD8+in-creased, and the degree of change is less than the ARH group, and recovered faster. Conclusions Immune function in patients after laparoscopic group was less changed, and recovered quickly, while the immune function were less inhibited, it may protect patients' immune function better.

Objective:To observe and study the short-term efficacy of levocarnitine combined with trimetazidine in the treatment of elderly heart failure of ischemic cardiomyopathy. Methods:Totally 106 elderly patients with ischemic cardiomyopathy and heart failure were randomly divided into the observation group and the control group with 53 ones in each. All the patients were given anti-platelet, anti-myocardial ischemia and lipid-lowering therapy as well as the conventional therapy on myocardial ischemia. The control group was treated with trimetazidine,20mg,po,tid,while the observation group was additionally treated with 2g levocarnitine with 0. 9% sodium chloride injections,100ml,ivd,qd. The treatment course was 4 weeks. The improvement of heart function and the changes in cardiac function indices( including LVEDD,LVESD and LVEF)and cardiac ischemia markers( CKMB,TüI and BüP)before and after the treatment were compared between the two groups. The incidence of adverse drug reactions,the rate of re-hospitalization and mortality in the two groups were also compared. Results:The significant efficiency and total effective rate in the observation group were much higher than those in the control group(P<0. 05 or 0. 000 1). After the treatment,LVEDD and LVESD in the two groups were declined, LVEF was increased(P<0. 05),and the changes in the observation group were more notable than those in the control group(P<0. 05 or 0. 000 1). After the treatment,the contents of CKMB,TüI and BüP in the two groups were lower than those before the treat-ment(P<0. 05),and the decrease in the observation group was more notable than that in the control group(P<0. 05). There were no significant differences in the incidence of adverse reactions,re-admission rate and mortality between the two groups(P>0. 05). Conclusion:Levocarnitine combined with trimetazidine on the basis of the conditional therapy in the treatment of elderly patients with ischemic cardiomyopathy and heart failure can effectively improve heart function with better clinical efficacy,which is worthy of promo-tion in clinic.