Pleckstrin homology-like domain family A member 1(PHLDA1)is a pro-apoptotic factor as well as a key regulator of metabolic diseases.In obesity-related diseases,PHLDA1 can reduce liver triglyceride production through inhibition of the expression of sterol regulatory?element binding proteins?1(SREBP?1),and reduce fat syn?thesis through inhibition of peroxisome proliferator?activated receptor γ(PPARγ).However,in cardiovascular dis?eases,PHLDA1 increases vascular calcification,dysfunction,thereby aggravates ischemia?reperfusion injury in the heart and brain.The dual role of PHLDA1 has also been confirmed in tumors.In summary,PHLDA1,as a multi?functional factor,plays different functional roles through various mechanisms.

Objective:To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B.Methods:175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC).Results:The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion:HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

Objective:To analyze the characteristics of drug resistance genes in a Klebsiella pneumoniae strain coproducing carbapenemases KPC-2 and NDM-5. Methods:Klebsiella pneumoniae KPN-hnqyy was separated from the stool specimen of a patient in the Hematology Department of Affiliated Cancer Hospital of Zhengzhou University. The strain was identified with a BD Phenix-M50 automated microbiology system and the minimum inhibitory concentration against the strain was measured as well. The genotypes of the carbapenemases were tested by enzyme immunochromatographic assay and PCR method. The transferability of related plasmids was analyzed by conjugation test. Whole-genome sequencing of the strain was conducted using PacBio and Illumina platforms. The MLST type, resistance gene and plasmid type of the strain were retrieved in BacWGSTdb. The genome and open reading frame sequence of the strain were compared using Easyfig_2.2.3. Visual cycle graphs were generated using BRIG v0.95. Results:Klebsiella pneumoniae KPN-hnqyy was resistant to carbapenem antibiotics. It belonged to ST11 and carried two carbapenemase genes of blaKPC-2 and blaNDM-5. The conjugant only harbored the blaKPC-2 gene. Whole-genome sequencing revealed that the strain contained one chromosome and three plasmids. Its chromosome genome shared more than 99.9% similarity with that of Klebsiella pneumonia KP69 and KP19-2029. Moreover, a similar IncR and IncFⅠ resistance gene fusion region was contained in different types of plasmids carried by them: the blaKPC-2 gene was located in a structure—which evolved from the Tn3-△Tn4401-Tn1721/Tn1722 sequence—inside this fusion region with its ends inserted into the transposase IS26 gene; the blaNDM-5 gene was located on a transposon containing the special plasmids of the insertion fragment in phages, with its ends inserted into the transposase IS26 gene too. Conclusions:The IncR and IncFⅡ resistance gene fusion region of blaKPC-2 carried by Klebsiella pneumoniae ST11 might be widely coexistent with the chromosomal genome. The blaNDM-5 gene carried by special plasmids might be accidentally obtained through gene recombination mediated by transposable element IS26. The wide transmission of Klebsiella pneumoniae ST11 carrying the blaKPC-2 gene in China and its ability to obtain other carbapenemase genes through transposable element IS26 were well worth attention.

Objective:To explore the expression and clinical significance of KIF20A in HER2-positive breast cancer.Methods:The clinicopathological characteristics of 82 cases of HER2-positive breast cancer were retrospectively analyzed. The expression of KIF20A in tissues was detected by immunohistochemical method, and the expression of KIF20A in HER2 overexpression breast cancer and its relationship with clinicopathological characteristics were analyzed. The mRNA level of KIF20A in HER2-positive breast cancer tissues and normal tissues adjacent to cancer were analyzed by bioinformatics methods.Results:The positive expression of KIF20A was in the nucleus, forming brown-yellow particles. In HER2-positive breast cancer tissues, the positive high expression rate of KIF20A is 57.3%, while it is mainly low or no expression in the adjacent tissues. The high expression of KIF20A is significantly correlated with tumor size and pTNM stage, while the correlation with age and tumor grade is not statistically significant. The results of bioinformatics analysis suggest that the high expression of KIF20A in invasive breast cancer is significantly related to poor disease-free survival.Conclusions:KIF20A is abnormally expressed in HER2-positive breast cancer, which is related to the tumor grade and pTNM stage of HER2 overexpression breast cancer, and the high expression of KIF20A indicates a poor prognosis.

Objective:To analyze the characteristics of plasmids in KPC-2-producing Serratia marcescens ( S. marcescens) isolates. Methods:Four carbapenem-resistant S. marcescens strains were isolated from four patients admitted to the hepatobiliary ward of Affiliated Cancer Hospital of Zhengzhou University in 2016. BD Phenix-100 was used to identify the strains and detect the minimum inhibitory concentrations (MICs). Homology analysis was performed using pulsed-field gel electrophoresis (PFGE). The modified Hodge test was used to detect the phenotypes of carbapenemase. PCR and gene sequencing were used to detect the types of carbapenem resistance genes. The transferability of plasmids was detected by conjugation test. The characteristics of plasmids were analyzed by genomic alignment method after whole genome sequencing. DNAMAN V9 software was used to compare the amino acid sequences of the replication initiation proteins. A phylogenetic tree was constructed with neighbor-joining method using MEGA7.0. Results:All of the four S. marcescens strains were resistant to carbapenem antibiotics. They were highly homologous according to PFGE. Hodge test results were all positive and the carbapenemase genotype was blaKPC-2. Conjugation test results were positive. The plasmid was a circular DNA of 42 742 bp in length. It had the similar skeleton of incX6 plasmid and the similar amino acid sequence of replication initiation protein. Moreover, it and incX6 plasmid were at the same node in the phylogenetic tree. The blaKPC-2 was located in the core of drug resistance, which was composed of insertion elements including Tn3 family transposons, recombinant enzyme genes, △ISKpn6 and ISKpn27. Conclusions:The plasmid was incX6-like. The blaKPC-2 gene was located in the transposon of △Tn6296. More attention should be paid to the bacteria carrying KPC-2 in incX plasmids.

Objective To investigate the role of CCAAT enhancer binding protein A (C/EBPα) in lung development by analyzing the relationship between dynamic expression of C/EBPα protein and cell differentiation in rat lung tissue.Methods According to the histological stages of rat lung development,lung tissues were collected on 15.5 d (the late pseudoglandular period),17.5 d (the canalicular period),19.5 d (the early saccular period) of embryonic age and at 12 h (the middle saccular period),on 4 d (the late saccular period),7 d (the alveolar period,the alveolar stage),14 d (the alveolar period,the equilibrium stage) of postnatal age.The lung morphologic appearance was observed by using HE staining.Western blot was used to detect the expressions of C/EBPα and surfactant Protein (SP)-A,SP-B,SP-C,SP-D.Phosphatidylcholine (PC) assay kit was utilized to analyze the secretion of PC.Periodic acid-schiff (PAS) staining was used to evaluate the amcunt of glycogen in lung tissue.Results (1) C/EBPαt and SP-A began to express on 15.5 d of embryonic age (0.36 ±0.02,0.01 ±0.01),while SP-B,SP-C and SP-D started to express on 17.5 d of embryonic age (0.33 ±0.06,0.01 ±0.01,0.11 ±0.08).All of them increased with the development of lung,and C/EBPα,SP-A,SP-C reached the highest level at 12 h of postnatal age (3.48 ±0.05,3.24 ± 0.19,1.26 ± 0.21),and SP-D on the postnatal 4 d (1.48 ± 0.10),then gradually decreased,while the expression of SP-B continued to rise.The levels of C/EBPα and SPs maintained stable on postnatal 14 d.The C/EBPα protein level was positively correlated with SPs at embryonic age of 15.5 d,17.5 d,19.5 d and postnatal age 12 h (r =0.999,0.991,0.982,0.951,all P ＜ 0.05).(2) The level of PC was very low at embryonic age of day 15.5 [(60.50 ± 1.30) μg/g].With the development of lung,the secretion of PC increased gradually,but there was no significant correlation between the expression of PC and C/EBPoα(all P ＞ 0.05).(3) The level of glycogen was high in the late pseudoglandular stage (15.5 d) (585.50 ± 2.20),the content of glycogen decreased with the development of lung,especially on the canalicular (embryonic day 17.5) and during early saccular period (embryonic day 19.5),and then it became stable during the alveolar period (postnatal age 7 d).The expression of C/EBPα had negative correlation with the content of glycogen in fetal lung(r =-1.000,P ＜ 0.01).Conclusion C/EBPα plays an important role in rat lung development,as it may promote lung maturation by regulating the synthesis and secretionof SPs and PC.

Objects: To clarify the risk factors of candidemia and to assess the clinical differences that may exist between infection with Candida parapsilosis and that with other Candida species in cancer patients. To statistically analyze the clinical characteristics of Candi-da albicans candidemia and C. parapsilosis candidemia and risk factors for their infections. We aimed at a timely intervention through this type of analysis to avoid susceptible factors and improve the prognosis of patients with candidemia. Methods: We retrospectively included 323 patients with candidemia in Affiliated Cancer Hospital of Zhengzhou University between March 2012 and February 2018 and analyzed the clinical characteristics of these patients to establish the risk factors of candidemia. We performed a comparative anal-ysis of the clinical characteristics of C. parapsilosis infections and non-parapsilosis Candida spp. infections and of C. albicans infections and non-albicans Candida spp. infections. In addition, drug sensitivity tests and analyses were performed with the common antifungal drugs used in Candida infections by a micro-broth dilution method. The statistical software SPSS version 22 was used for the analyses. Results: A total of 323 patients were enrolled and analyzed in this study. Of the isolates, 34.37% were C. albicans and 65.63% were non-albicans Candida spp. Multivariate regression analysis showed that the following factors were associated with the occurrence of C. parapsilosis candidemia: parenteral nutrition (P<0.001), neutropenia (P<0.001), history of receiving chemotherapy (P=0.002), and history of previous antifungal use (P<0.001). Parenteral nutrition was found to be an independent risk factor for C. albicans candi-demia (OR=0.183; 95%CI:0.098?0.340; P<0.001). Conclusions: C. parapsilosis was found to be the primary pathogen in cancer patients with candidemia. Total parenteral nutrition in the intensive care unit at diagnosis and abdominal surgery were independent risk factors of candidemia, and parenteral nutrition was an independent risk factor of C. parapsilosis candidemia. At present, C. parapsilosis is sur-passing C. albicans as the main pathogen of candidemia in cancer patients at our hospital. This study emphasizes the need to assess the possible risk factors for candidemia in cancer patients and aims at strengthening and developing a hospital-based control strategy to prevent the spread of candidemia.

OBJECTIVE： To study the vasodilatory effect of oxysophocarpine （OSC） on isolated thoracic aortic rings of rats and its possible mechanism. METHODS： Thoracic aortic rings of rats were collected （called “vascular ring” for short）. Using K-H nutrient solution as blank control and the diastolic rate as index， the effects of different concentrations （0.2-1.0 mg/mL） of OSC on normal vascular rings in basal state， normal or endothelium-free vascular rings pre-contracted by norepinephrine （PE， 1×10－6 mol/L） were investigated. After pre-culturing normal thoracic aortic rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester（L-NAME）and cyclooxygenase inhibitor indomethacin（INDO），as well as pre-culturing endothelium-free vascular rings by potassium ion channel blocker BaCl2，tetraethylammonium（TEA）and 4-aminopyridine（4-AP）， the diastolic effects of OSC of different concentrations （0.2-1.0 mg/mL） on the above vascular rings were investigated by using the same method. RESULTS： Compared with blank control， there was no significant effects of different concentrations of OSC on the diastolic rate of normal vascular rings in basal state （P＞0.05）， but 0.4-1.0 mg/mL OSC could significantly improve the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＜0.01）， in concentration-dependent manner. After preculturing with L-NAME， INDO， 4-AP and BaCl2， different concentrations of OSC had no significant effect on the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＞0.05）. After pre-culturing with TEA and Gli， 0.4-1.0 mg/mL OSC could significantly reduce the diastolic rate of endothelium-free vas- cular rings pre-contracted by PE （P＜0.01）. CONCLUSIONS： OSC did not significantly dilate the thoracic aortic rings of rats in the basal state within the dose range （0.2-1.0 mg/mL）， but OSC of 0.4-1.0 mg/mL have significant diastolic effects on the normal or endothelium-free thoracic aortic rings of rats pre-contracted with PE. The mechanism of thoracic aortic rings dilation is endothelium-independent， which may be associated with receptor operational calcium channel，Ca2+-activated potassium channels and ATP-sensitive potassium channels.

Objective To investigate the clinical significance of heart fatty acid binding protein (H-FABP) and pregnancy associ-ated plasma protein A(PAPP-A) in acute coronary syndrome(ACS) .Methods A case-control study was conducted in 60 patients with ACS ,45 patients with stable angina pectoris (SAP) and50 patients without coronary heart diseases (control group) .All plasma samples were tested H-FABP and PAPP-A .Results Concentrations of H-FABP and PAPP-A were significantly different among the 3 groups(P<0 .01) .H-FABP and PAPP-A in ACS group were significant higher than those of SAP group and control group (P<0 .01) ,however there were no significant differences between SAP and control group (P>0 .05) .The sensitivity and specificity of H-FABP were 91 .7% and 78 .0% respectively analyzed by ROC curve .Similarly ,the sensitivity and specificity of PAPP-A were 48 .3% and 98 .0% respectively .The correlation of H-FABP and PAPP-A was high(r=0 .835 ,P<0 .01) according to the analysis by Pearson correlation analysis .Conclusion Concentrations of plasma H-FABP and PAPP-A had close relationship with ACS ,the sensitivity of H-FABP was much higher ,both of which could be the potential biomarkers and contributed to the diagnosis of exist-ence and progress of ACS .

Objective To reveal the pancreatic cancer cell drug resistance mechanism to provide a basis for clinical treatment by studying miR-26b targeting p53 for promoting the drug resistance of pancreatic cancer cell line PANC-1 .Methods (1) The over-expression and knockdown plasmid of p53 and the fluorescent reporter vector containing 3′Untranslated region(3′UTR) were constructed respectively .(2) The effect of p53 and miR-26b on the growth and proliferation of PANC-1 was investigated by methyl thiazolyl tetrazolium(MTT) in the presence of gemcitabine .(3) The target relationship between miR-26b and p53 was determined by bioinformatics ,real-time polymerase chain reaction(PCR) ,fluorescent reporter vector and Western blot experiment .(4) The effect of p53 on the growth of miR-26b was investigated by salvage experiments .Results (1) The MTT experiment confirmed that ,in the presence of gemcitabine ,over-expression of p53 could inhibit the proliferation of pancreatic cancer cell line PANC-1 ,and knock-down of p53 could promote the growth and proliferation of PANC-1;(2) the bioinformatics prediction showed that miR-26b targeted p53 ,real-time PCR ,Western blot and fluorescent reporter vector experiment confirmed that p 53 is the target gene of miR-26b , and miR-26b inhibits transcription and translation of p53 by targeting the 3′UTR of p53 gene;(3) the MTT experiment confirmed that in the presence of gemcitabine ,over-expression of miR-26b could promote the growth and proliferation of PANC-1 cells ,and enhanced its resistance to gemcitabine ;(4) the rescue experiment confirmed that the simultaneous over-expression of p53 rescued the drug resistance promoting effect of miR-26b on PANC-1 .Conclusion miR-26b inhibits the expression of p53 by targeting 3′UTR of the p53 gene and enhances the drug resistance of pancreatic cancer cell line PANC-1 to gemcitabine .