Objective To investigate the expression of PED/PEA-15 mRNA and protein in esophageal carcinoma tissue and their clinical significances.Methods The expression of PED/PEA-15 mRNA was detected by RT-PCR,and the expression of PED/PEA-15 protein was measured by immunohistochemistry in 50 cases of esophageal carcinoma,50 cases of corresponding paracarcinoma tissue,and 50 cases of corresponding normal esophageal tissue.Results The expression of PED/PEA-15 mRNA was 1.14±0.49 in esophageal carcinoma,which was significantly higher than that in para-carcinoma tissue (0.59±0.31) and normal esophageal carcinoma tissue (0.53±0.22) (F =44.085,P ＜ 0.001).The immunohistochemistry results showed that PED/PEA-15 protein expression was significantly higher than that in para-carcinoma tissue and normal esophageal tissue (x2 =36.967,P ＜ 0.001; x2 =26.272,P ＜ 0.001).The expression of PED/PEA-15 mRNA and protein were significantly associated with pathological grade,clinical stage of esophageal carcinoma (P ＜ 0.05),but were not significantly correlated to the age of onset,gender,pathological types (P ＞ 0.05).Conclusion The expression of PED/PEA-15 mRNA and protein are increased in esophageal carcinoma,which may play an important role in the occurrence and development of esophageal carcinoma.

Objective:To investigate the effect of enhanced external counterpulsation(EECP)on heart failure with preserved ejection fraction(HFpEF)and hemodynamics in elderly patients.Methods:Clinical data of 66 elderly HFpEF patients admitted to the enhanced external counterpulsation center of our hospital from January 2018 to December 2019 were retrospectively analyzed.The primary assessment parameter was the six-minute walk distance, and the secondary parameters included the Minnesota Living with Heart Failure Questionnaire(MLHFQ). Noninvasive hemodynamic parameters including the cardiac index(CI), stroke volume(SV), isovolumic relaxation period(A2-mitral valve opening, A2-O), pulmonary capillary wedge pressure(PCWP)and total peripheral resistance(TPR)were monitored and mean arterial blood pressure(MAP)was calculated.Results:After EECP treatment, the six-minute walk distance increased(372±87 m vs.341±85 m, P<0.05), the score of MLHFQ decreased(47.0±16.0 vs.50.0±17.0, P<0.05), CI increased(2.8±0.7)L·min -1·m -2vs.(2.6±0.6)L·min -1·m -2( P<0.05), SV, PCWP and A2-O did not show significant change(73.3±16.4 ml vs.71.5±17.1 ml, 10.0±3.3 mmHg vs.11.0±3.6 mmHg, 1 mmHg=0.133 kPa, 98.0±29.5 ms vs.91.0±29.1 ms, P>0.05), TPR decreased(1 719.0±427.0 DS/cm 5vs.1 821.0±508.0 DS/cm 5, P<0.05), and there was no significant change in MAP(96.9±10.7 mmHg vs.98.8±13.1 mmHg, P>0.05), compared with pre-EECP treatment levels.Compared with patients without hypertension, MAP decreased in patients with hypertension(14 cases), when stratified by the initial MAP( P<0.05). Conclusions:For elderly patients with HFpEF, EECP can increase the six-minute walk distance, improve the quality of life and hemodynamic parameters, and is a safe adjuvant treatment.

OBJECTIVE:To study the inhibition effect of spinosin on 7 subtypes (CYP2B6,CYP2C8,CYP2C9,CYP2D6, CYP1A1,CYP2C19 and CYP3A4)of cytochrome P450(CYP450)enzymes from human liver microsomes in vitro. METHODS:Tak-ing 200.00,100.00,50.00,25.00,12.50,6.25,3.13,1.56,0.78,0.39 μmol/L spinosin and human liver microsomes for incuba-tion,using daktarin,bupropion,amodiaquine hydrochloride,diclofenac sodium,mephenytoin,dextromethorphan hydrobromide and midazolam as the specific probe drugs for above-mentioned 7 subtypes of CYP450 enzymes. UPLC-Q-TOF-MS was conducted to detect generation amount of 7 probe drug metabolites,and the half inhibitory concentration (IC50) of spinosin on 7 subtypes of CYP450 enzymes from human liver microsomes was calculated. RESULTS:IC50 of spinosin on 7 subtypes of CYP450 enzymes from human liver microsomes were 1714,1158,226.1,2288,80.59,101.1,1119 μmol/L,respectively,which were higher than 50μmol/L. CONCLUSIONS:Spinosin has no inhibition effect on above-mentioned 7 subtypes of CYP450 enzymes from human liver microsomes,with very low probability of inducing metabolic drug interactions.

Objective To investigate the effect of FEZ family zinc finger 1-antisense RNA 1(LncRNA FEZF1-AS1)targeting regulation of miR-200c-3p expression on biological behaviors of human lung fibroblasts(HLF).Methods Transforming growth factor β1(TGF-β1)was used to induce the transformation of HLF into myofibroblasts,which were divided into the Blank group and the model group(HLF+TGF-β1 group).According to different transfection plasmid,cells were divided into the Blank group,the TGF-β1+Si LncRNA FEZF1-AS1 NC group and the TGF-β1+Si LncRNA FEZF1-AS1 group.The protein expressions of α-SMA,Collagen Ⅰ and Vimentin were detected by Western blot assay.The expressions of LncRNA FEZF1-AS1 and miR-200c-3p were detected by quantitative real-time PCR(qRT-PCR).Cell proliferation ability was detected by CCK-8 method,migration ability was detected by cell scratch experiment and invasion ability was detected by Transwell assay.The targeting relationship between FEZF1-AS1 and miR-200c-3p was detected by dual-luciferase reporter assay.Results Compared with the Blank group,protein expressions of α-SMA,Collagen Ⅰ,Vimentin and the expression of LncRNA FEZF1-AS1 were increased in the HLF+TGF-β1 group(P＜0.05),and the expression of miR-200c-3p was decreased(P＜0.05).Compared with the TGF-β1+Si LncRNA FEZF1-AS1 NC group,cell proliferation,migration,invasion ability,LncRNA FEZF1-AS1 expression,protein expressions of α-SMA,Collagen Ⅰ and Vimentin were decreased in the TGF-β1+Si LncRNA FEZF1-AS1 group(P＜0.05),and the expression of miR-200c-3p was increased(P＜0.05).There were binding sites between miR-200c-3p and FEZF1-AS1 gene sequence.Conclusion LncRNA FEZF1-AS1 promotes the formation and progression of idiopathic pulmonary interstitial fibrosis by inhibiting miR-200c-3p.

Objective:To study the performance of immune reconstitution in patients with chimeric antigen receptor (CAR)-T cell immunotherapy bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 61 patients with acute B lymphocytic leukemia (B-ALL) who received CAR-T cell bridging allo-HSCT in Beijing Lu Daopei Hospital from August 2018 to December 2021 were enrolled, and the clinical medical records of the above patients were retrospectively analyzed. The average age was 14 (7, 30) years old, including 39 males and 22 females. 32 patients were treated with CAR-T cell immunotherapy(CAR-T Group) and 29 didn't with CAR-T cell immunotherapy(non-CAR-T group). The follow-up period was 561 (235,784) days. Multicolor flow cytometry was used to detect the peripheral blood lymphocyte subsets, i.e. total lymphocytes, T lymphocytes, helper T cells, cytotoxic T cells, B lymphocytes, NK cells, and Treg cell counts before transplantation and 1, 2, 3, 6, 8, 10, and 12 months after transplantation, to evaluate the immune reconstitution performance post allo-HSCT.Results:Serum globulin before transplantation: The IgA level in the CAR-T group was 0.18 (0.06, 0.49) g/L, which was lower than that of 1.03 (0.63, 1.56) g/L in the non-CAR-T group ( U=103.5, P<0.001). The IgG level in the CAR-T group was 5.54 (4.04, 7.09) g/L, lower than that of 6.78 (5.27, 9.26) g/L in the non-CAR-T group, ( U=1 298.5, P=0.017), and the IgM level in the CAR-T group was 0.18 (0.05, 0.30) g/L, lower than that of 0.40 (0.26, 0.71) g/L in the non-CAR-T group ( U=166.0, P<0.001). In the CAR-T group before transplantation, the absolute count of total lymphocyte in peripheral blood was 833.00 (335.00, 1 727.50) /μl, lower than that of 1 052.00 (545.75, 1 812.50) /μl in the non-CAR-T group ( U=404.0, P<0.001). The absolute count of T lymphocyte in the CAR-T group before transplantation was 686.00 (233.00, 1 307.00)/μl, lower than that of 860.00 (391.00, 1 419.75) /μl in the non-CAR-T group ( U=406.0, P<0.001). The absolute count of helper T lymphocytes in the CAR-T group was 146.00 (40.50, 327.50) /μl, lower than that of 162.50 (66.00, 384.75) /μl in the non-CAR-T group ( U=494.0, P=0.002). The absolute count of cytotoxic T lymphocytes in the CAR-T group was 343.00 (56.50, 924.00) /μl, lower than that of 478.00 (143.50, 992.25) /μl in the non-CAR-T group ( U=483.5, P=0.001). The absolute count of B lymphocytes in CAR-T group was 22.00 (6.00, 186.00) /μl, lower than that of 33.00 (8.00, 220.00) /μl in the non-CAR-T group ( U=498.0, P=0.002). And when two groups of patients were monitored after transplantation, there was no statistical difference in absolute cell counts of each immune cell subpopulation( P>0.05). Comparing the clinical features of the two groups, the pre-transplant history of the CAR-T group was 981.00 (368.50, 1 514.75) d, longer than that of 323.00 (167.50, 450.50) d in the non-CAR-T group ( U=263.0, P=0.004). The dose of rabbit anti-human thymic immunoglobulin (ATG) in the pretreatment protocol of patients in the CAR-T group was 5.00 (5.00, 7.50) mg/Kg, lower than that of 7.00 (5.00, 7.50) mg/kg in the non-CAR-T group ( U=288.5, P=0.018). The infusion dose of CD34 +cells in the CAR-T group was 5.91 (4.23, 6.02) ×10 6/kg, higher than that of 4.51 (4.00, 5.93)×10 6/kg in the non-CAR-T group ( U=291.0, P=0.012). The duration of the application of cyclosporine after transplantation in the CAR-T group was 167.00 (119.25, 299.50) d, which was shorter than that of 197.00 (102.50, 450.50) d in the non-CAR-T group ( U=421.0, P=0.001). Conclusions:For patients in CAR-T group with low immune function before transplantation, it may be possible to make them comparable to non-CAR-T group in immune reconstitution state by reducing the dose of pretreatment ATG, increasing the counts of CD34 + cells infusion in the graft, and discontinuing cyclosporine as soon as possible after transplantation.

Objective:This study aimed to evaluate the effect of enhanced external counterpulsation(EECP)on left ventricular function in elderly patients with coronary slow flow phenomenon(CSFP)using two-dimensional speckle tracking echocardiography(2D-STE).Methods:This prospective case-control study included 30 patients aged ≥60 years with no stenotic lesions in the coronary arteries but with slow blood flow phenomenon in more than one major coronary artery who were treated at the Department of Geriatrics, Qilu Hospital, Shandong University, between December 2017 and December 2018, and were divided into a medication group with 16 participants and a medication plus EECP group with 14 participants, using the numerical lottery method.Patients in the group treated with EECP received 6-week 36-h EECP therapy in addition to lifestyle modification and drug treatment.Fourteen patients with normal coronary blood flow served as the control group.Conventional echocardiography and 2D-STE were used to evaluate changes in left ventricular function in the CSF patients before and after drug treatment and EECP.Results:Compared with the control group before treatment, patients in the drug treatment group and the drug treatment plus EECP group showed a decrease in mitral annular early diastolic velocity( P<0.01), an increase in the ratio of peak mitral early diastolic blood flow velocity to the mean peak mitral annular early diastolic velocity( P<0.05), and a decrease in left ventricular longitudinal strain during systole( P<0.01), the longitudinal systolic myocardial strain rate( P<0.01)and the early diastolic longitudinal peak strain rate( P<0.01).There was no statistically significant difference in values from conventional echocardiographic parameters before and after treatment in CSF patients of the medication group(all P>0.05).In the group receiving EECP, there were statistically significant differences in pre-and post-treatment values in ventricular septal early diastolic velocity[(6.22 ± 0.64)cm/s vs.(6.69 ± 0.44)cm/s], lateral wall early diastolic velocity[(8.01±0.68)cm/s vs.(8.41±0.29)cm/s], mitral valve to mitral annulus early diastolic peak velocity ratio[(10.51±1.38) vs.(9.74±0.37)], longitudinal left ventricular systolic strain[(-16.21±0.46)% vs.(-16.80±0.48)%], left ventricular systolic longitudinal strain rate[(-1.29±0.03)s -1vs.(-1.35±0.04)s -1], and early diastolic longitudinal strain rate[(1.35±0.03)s -1vs.(1.40±0.03)s -1](t-values were -3.70、-2.74、2.23、10.25、12.30、-19.15, all P<0.05). Conclusions:2D-STE can evaluate subclinical myocardial dysfunction early and quantitatively in elderly patients with CSF, and objectively reflect changes in left ventricular function before and after clinical intervention with EECP.

Objective To investigate the comprehensive improvement of multi-system diseases in elderly patients treated with enhanced external counterpulsation(EECP).Methods Clinical data of an elderly patient with multiple systemic diseases were collected and analyzed.The therapeutic effect of EECP was assessed and EECP-related literatures were reviewed.Results The 62-year-old male patient was diagnosed with coronary atherosclerotic heart disease,unstable angina,New York Heart Association(NYHA)functional class Ⅱ,hypertension(grade 3,very high risk),type 2 diabetes,acute cerebral infarction (recovery period)and benign prostatic hyperplasia.After two courses of EECP treatment,angina in the patient was significantly relieved,cardiac systolic and diastolic function was improved,activity tolerance was increased and the corresponding dosage of therapeutic drugs was reduced.In addition,the patient's blood pressure and blood glucose levels were decreased after versus before treatment and the retinal superficial blood flow was enhanced in both eyes assessed by optical coherence tomography.The frequency and volume of nocturia were reduced.The symptoms of numbness on the left side were improved.Conclusions EECP treatment has shown significant therapeutic effects on multi-system diseases in the elderly patient.EECP is safe,effective and simple and has a broad application prospect in geriatrics.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.