Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Aim To explore the mechanism of Yanghe decoction-containing serum on the migration and inva-sion of MCF-7 breast cancer cells in a co-culture sys-tem with M2 tumor-associated macrophages(TAMs)based on the paracrine epidermal growth factor(EGF)/epidermal growth factor receptor(EGFR)sig-naling pathway.Methods The M2-type TAMs model was induced from THP-1 monocytic cell line through in vitro treatment with phorbol 12-myristate 13-acetate(PMA)and recombinant human macrophage colony-stimulating factor(M-CSF).The MCF-7 cells were co-cultured with M2-type TAMs using a Transwell non-contact co-culture system to evaluate their effects on migration and invasion.Subsequently,the cells were intervened with serum containing Yanghe decoction,and the proliferation of MCF-7 cells was detected using the CCK-8 assay,while their lateral migration ability was assessed through scratch assays.The invasion and vertical migration abilities of the cells were evaluated separately using Transwell assays,and the concentra-tion of EGF was measured using ELISA.Finally,the expression of EGFR,MCP-1,and MMP9 proteins was detected using Western blot.Results Compared to the control group,Yanghe decoction-containing serum in-hibited the proliferation of MCF-7 cells before and after co-culture.The serum reduced the scratch healing a-bility before and after co-culture and decreased their migration and invasion abilities.Additionally,Yanghe decoction-containing serum reduced the levels of EGF before and after co-culture and decreased the expres-sion of EGFR,MCP-1,and MMP9 proteins before and after+co-culture.Conclusion Yanghe decoction-containing serum can inhibit the migration and invasion of breast cancer MCF-7 cells before and after co-cul-ture with M2 TAMs.This effect may be related to the inhibition of the EGF-EGFR signaling pathway.

AIM To investigate the effects of stir-frying,processing with butter and carbonizing by stir-frying on oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis.METHODS The volatile oils and fatty oils were extracted by steam distillation method and Soxhlet extraction method,respectively,after which the extraction rates were determined.GC-MS was applied to analyzing the kinds and relative contents of oil components,after which cluster analysis was performed.RESULTS After the processing,the two medicinal materials demonstrated increased extraction rates of fatty oils and decreased extraction rates of volatile oils(except for processing with butter),the extraction rates of oil components in Gleditsiae sinensis Fructus were higher than those in Gleditsiae Fructus Abnormalis,and the reduced relative contents of toxic olefin benzene components were observable.CONCLUSION The kinds and relative contents of oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis exist obvious differences,the former displays better medicinal quality,whose processing mechanism in alleviating dryness and strength may contribute to the reduction of relative contents of toxic olefin benzene components.

In non-small cell lung cancer(NSCLC),as an improtant oncogenic driver gene,epidermal growth factor receptor exon 20 insertion(EGFR ex20ins)has a unique protein structure and is primarily drug-resistant to tradi-tional EGFR-tyrosine kinase inhibitors(EGFR-TKIs).In recent years,exploration of targeted therapy for EGFR ex20ins has never stopped.Firstly Mobocertinib and Amivantamab obtained approval from U.S.Food and Drug Administration(FDA)for EGFR ex20ins mutant NSCLC patients,then other drugs,such as Sunvozertinib,made breakthroughs and combination therapies also obtained gains.Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance.As men-tioned above,it's definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess ef-fect and difference between novel drugs.This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.

Objective:We genetically modified our non-replicating vaccinia virus NTV to improve its immunogenicity.Methods:We constructed NTV-modified strain NTV-ΔF1L-C7L by homologous recombination of vaccinia virus based on CRISPR-Cas9 technology by inserting the C7L gene while deleting the F1L gene. The recombinant virus NTV-ΔF1L-C7L was then immunized with 10 7 PFU in BALB/c mice, and the levels of humoral and cellular immunity induced by NTV-ΔF1L-C7L were detected by ELISA and ELISpot method, respectively, and the levels of neutralizing antibodies were determined by the phage-reduced neutralization assay. Results:The PCR and western- blot identification proved that the F1L gene of the constructed NTV-modified strain NTV-ΔF1L-C7L was missing, while the C7L gene was inserted back in the region, and the C7L gene could be expressed normally, indicating that the recombinant virus was constructed correctly. After immunization of mice with NTV-ΔF1L-C7L, ELISA result showed that the recombinant virus NTV-ΔF1L-C7L induced a higher level of IgG antibody than NTV; ELISpot result also showed that the recombinant virus was able to induce a higher level of IFN-γ; and the result of plaque reduction neutralization test showed that the recombinant virus was able to induce a higher level of IFN-γ antibody than that of NTV.Conclusions:We correctly constructed the NTV gene-modified strain NTV-ΔF1L-C7L, which induced stronger humoral and cellular immunity compared with NTV, and provided reference data for the research and development of replacement products for smallpox or monkeypox vaccines.

Objective To investigate the assessment of fetal lung maturity using main pulmonary artery accelerated systolic time(AT)/ejection time(ET)ratio in patients with severe preeclampsia.Methods A total of 65 pregnant women who were hospitalized in our hos-pital due to severe preeclampsia,from January 2021 to December 2022,and voluntarily underwent ultrasound examination were enrolled in this study.The patients were divided into early-onset(20 to 33+6 weeks gestation)severe preeclampsia group(group A,n= 30)and late-onset(34 to 40 weeks)severe preeclampsia group(group B,n= 35).Healthy pregnant women with gestational age-matched to groups A and B via ultrasound examination were selected as controls(n= 30 andn= 35,respectively).Fetal main pulmonary artery blood flow parameters were measured using ultrasound Doppler:AT,ET,AT/ET,and peak systolic flow rate(PSV).Amniotic fluid(approximately 15 mL)was collected immediately after delivery,and the lecithin/sphingomyelin(L/S)values were measured.The blood flow parameters of the main pulmonary artery of the fetuses in groups A and B were compared,and whether there was any difference between them and the control group was analyzed.The correlation between the blood flow parameters and amniotic fluid L/S was also analyzed.Results There were statistically significant differences in AT,ET,AT/ET,and PSV in the fetal main pulmonary artery between groups A and group B(P＜0.05),and all of them were smaller than those in the control group(P＜0.05).The AT/ET ratio of the fetal main pulmonary artery in groups A and B was positively correlated with amniotic fluid L/S(r= 0.821 and 0.383,respectively,P＜0.05).Receiver operating charac-teristic curve analysis showed that the area under the curve of AT/ET in the diagnosis of early-onset and late-onset preeclampsia was 0.839 and 0.833,respectively,and the sensitivity was 0.853 and 0.912,the specificity was 0.583 and 0.611,and the cut-off values were 0.185 and 0.255,respectively.The false positive rate was 5%.Conclusion The AT/ET value of the fetal main pulmonary artery can be used to make a preliminary diagnosis of severe preeclampsia and quantitatively assess fetal lung maturity,which can provide a new,simple,non-invasive,and reproducible assessment method for clinical practice.

Angiopoietin-like protein (ANGPTL), a group of secreted glycoproteins, is widely expressed in vivo and is involved in many pathophysiological processes such as glycolipid metabolism, stem cell growth, local inflammation, vascular leakage and angiogenesis. Many kinds of ANGPTL are closely related to the occurrence and development of diabetic retinopathy (DR), especially ANGPTL4, which has gradually become a new hotspot in the field of DR Research. ANGPTL is involved in glucose metabolism and lipid metabolism, promotes increased vascular permeability, pathological angiogenesis, and participates in intraocular inflammation. ANGPTL is a promising molecular target. It can not only be used as a biomarker to predict the occurrence and progression of DR, but also provide new ideas for the treatment of DR by making antibody drugs to interfere with this molecule.

ObjectiveTo explore the mechanisms of Astragali Radix-Curcumae Rhizoma （HQ-EZ） in alleviating hypercoagulability and inhibiting tumor growth and metastasis by modulating the formation of neutrophil extracellular traps （NETs） via the complement component 5a （C5a）/C5a receptor （C5aR） pathway. MethodForty male C57BL/6 mice were randomized into four groups： Blank， model， HQ-EZ （8.2 g·kg^-1）， and PMX53 （1 mg·kg^-1）. The mouse model of Lewis lung cancer was established in other three groups except the blank group. Mice were administrated with corresponding drugs from day 3 after modeling. Specifically， the HQ-EZ decoction was administrated for 14 consecutive days， while intraperitoneal injection of PMX53 was implemented on days 3， 6， 9， 12， and 15. Mouse body weight and tumor diameter were measured every two days. On the next day of the last administration， lung microCT was performed to observe the tumor metastasis in vivo. Blood samples were collected from the eyeball after anesthetization， and tumor and lungs were collected after the mice were sacrificed. Tumor weight was measured to calculate the tumor growth inhibitory rate. Enzyme-linked immunosorbent assay was employed to measure the levels of C5a， neutrophil elastase （NE）， citrullinated histone-H3 （Cit-H3）， myeloperoxidase （MPO）， matrix metallopeptidase-9 （MMP-9）， NETs， von Willebrand Factor （vWF）， tissue factor （TF）， and P-selectin in the serum and tumor tissue. Terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling was conducted to assess apoptosis in the tumor tissue. Hematoxylin-eosin staining was conducted to observe lung metastasis， and immunofluorescence （IF） was employed to observe the expression of NETs in the tumor tissue. Western blot was employed to determine the protein levels of C5aR， MPO， and Cit-H3 in the tumor tissue. ResultCompared with the blank group， the model group had nodules in the lung， increased areas with low X-ray transmittance， appearance of nodular foci and multiple hemorrhagic foci in the lungs， and darkening lung color. Furthermore， the modeling elevated the serum levels of C5a， NETs and related proteins， vWF， TF， and P-selectin （P<0.01）. Compared with the model group， HQ-EZ and PMX53 reduced the lung metastases， areas with low X-ray transmittance， and nodules in the lungs and lightened the lung color. Compared with the model group， the two drug intervention groups showed flat tumor growth curves， decreased tumor weight （P<0.01）， increased apoptosis of tumor cells （P<0.01）， lowered levels of C5a， NETs and related proteins， vWF， TF， and P-selectin both in the serum and tumor tissue （P<0.05）， and down-regulated protein levels of C5aR， MPO， and Cit-H3 （P<0.05）. ConclusionHQ-EZ inhibited the expression of NETs by suppressing the C5a/C5aR pathway， thereby alleviating hypercoagulability and inhibiting tumor growth and metastasis.

BACKGROUND:As a leading technique in the treatment of primary stenosis by posterior spinal endoscopy through unilateral approach and bilateral decompression using single channel endoscopy,the long-term efficacy needs to be further observed.There are few reports on the scope of intraoperative resection and few relevant studies on biomechanics and finite element analysis. OBJECTIVE:A three-dimensional finite element model was established to evaluate the effects of bilateral lumbar canal decompression under a one-hole split endoscope on lumbar range of motion and intradiscal pressure,to provide suggestions for clinical operation and theoretical basis for further clinical research. METHODS:A complete L3-L5 vertebral body model was reconstructed by CT images of nine healthy volunteers,which was used as the preoperative model M1.The simulated surgical resection range of L4-L5 was performed,and 1/4,1/3 and 1/2 of bilateral facet joints were removed respectively to obtain models M2,M3 and M4.The range of motion and the maximum Von Mises stress of the four models were compared in the six directions of forward bending,backward extension,left and right bending,and left and right rotation. RESULTS AND CONCLUSION:(1)The L3-L5 finite element model established in this study was effective,and the range of motion was within the range of previous solid studies under six motion states.(2)Compared with the M1 model,the L4-L5 lumbar spine range of motion increased with the increase of resection range in M2 with M3 and M4 models under forward bending,left and right bending and left and right rotation loading,and the difference was significant(P＜0.05).Under posterior extension loading,there was no significant difference in lumbar range of motion between M1 and M2(P＞0.05),but there was a significant difference of M1,M3 and M4(P＜0.05).(3)The range of motion of the L3-L4 lumbar spine had no significant change with the increase of bilateral facet arthrotomy(P＞0.05).(4)There was a significant difference in the maximum value of L4-L5 Von Mises between M1 and M2(P＜0.05),and there was a significant difference in the maximum value of L4-L5 Von Mises between M1 and M3,M4(P＜0.01),and the maximum value of L4-L5 lumbar von Mises increased with the increasing range of bilateral facet joint resection.Resection of more than 1/3 was particularly obvious.(5)The maximum value of Von Mises in the L3-L4 lumbar spine was increased with the increase of the resection range under forward bending,left and right bending and left and right rotation loading and the difference was significant(P＜0.05).(6)The results exhibited that the L4-L5 lumbar motion and intervertebral disc pressure increased with the increase of the excision range.Intervertebral disc pressure at L3-L4 increased with the increased extent of excision,but the lumbar range of motion was not significantly affected.In conclusion,the stability of the operative segment may be affected by the increase in the scope of facet joint resection.Although the immediate stability of adjacent segments is not affected,it may accelerate disc degeneration.

OBJECTIVE To investigate the correlation between the expression levels of tissue inhibitor of metalloproteinases 1(TIMP-1)and drosophila mothers against DDP homolog 4(Smad4)in vocal cord precancerous lesions and postoperative recurrence and malignant transformation.METHODS The clinical and pathological data of 162 patients with vocal cord precancerous lesions admitted to the First Affiliated Hospital of Zhengzhou University from August 2018 to August 2021 were retrospectively analyzed.The expression of TIMP-1 and Smad4 in the surgically removed precancerous tissues(precancerous lesion group)and adjacent normal mucosal tissues(control group)were detected by immunohistochemical method.The relationship between the positive rate of TIMP-1 and Smad4 and clinicopathological features was analyzed.Kaplan-Meier method and Cox regression analysis were used to analyze the effect on postoperative recurrence and malignant transformation.RESULTS Compared with the normal mucosa of the control group,the positive rate of TIMP-1 was higher and the positive rate of Smad4 was lower in the precancerous lesion group(P<0.05).The positive rates of TIMP-1 and Smad4 in patients with different lesion ranges,anterior commissure involvement and different degree of epithelial dysplasia were different(P<0.05).Postoperative follow-up lasted from 24 to 60 months,with a median follow-up time of 36 months.During the follow-up,6 patients were lost to follow-up,with a follow-up rate of 96.30%(156/162).During the follow-up,35 patients had postoperative recurrence(21.60%)and 16 patients had postoperative malignant transformation(9.88%).Kaplan-Meier survival analysis showed that the postoperative recurrence rate and malignant change rate of TIMP-1 positive patients were higher than those of TIMP-1 negative patients(P<0.05),amd the recurrence rate and malignant change rate of Smad4-negative patients were higher than those of Smad4-positive patients(P<0.05).Multivariate Cox regression analysis showed that laryngeal reflux,lesion scope>1/2,moderate/severe dysplasia,TIMP-1 positive and Smad4 negative were independent risk factors for recurrence(P<0.05),and age>60 years old,anterior union involved,TIMP-1 positive and Smad4 negative were independent risk factors for malignant transformation(P<0.05).CONCLUSION The patients with high expression of TIMP-1 and low expression of Smad4,positive expression of TIMP-1 and negative expression of Smad4 have higher risk of postoperative recurrence and malignant transformation.