1.Difference in drug resistance of pathogens causing early-and late-onset ventilator-associated pneumonia in an intensive care unit
Shuke JIANG ; Biaofeng LUO ; Rongming LI ; Xiaoyan CHEN ; Chunfeng LI ; Yongnan XU ; Lin LI ; Zhenkai TAO
Chinese Journal of Infection Control 2014;(4):208-211
Objective To study the incidence of ventilator-associated pneumonia(VAP)and antimicrobial resistance of pathogens in an intensive care unit(ICU).Methods The occurrence of VAP in hospitalized patients with mechan-ical ventilation>48 hours between January 2011 and December 2012 were investigated,species and antimicrobial re-sistance of pathogens causing early onset-VAP (E-VAP,mechanical ventilation≤4 d)and late-onset VAP(L-VAP, mechanical ventilation>4 d)were compared.Results A total of 1 76 patients were investigated,incidence of VAP was 44.32% (78 cases);With the prolongation of mechical ventilation,incidence of VAP increased gradually (χ2=52.561,P<0.001).The incidence of L-VAP was significantly higher than E-VAP (58.33% [70/120]vs 14.29%[8/56])(χ2= 30.02,P<0.001).A total of 178 pathogens were isolated,gram-negative bacteria,gram-positive bac-teria and fungi were 104(58.43% ),46(25.84% ),and 28(15.73% )isolates respectively;97(54.49% )multidrug-resistance/pandrug resistance organisms (MDRO)were isolated. MDRO isolation rate in L-VAP patients was high-er than E-VAP patients([58.86% ,n= 93]vs [20.00% ,n= 4]),resistance rate of major pathogens causing L-VAP was significantly higher than E-VAP patients(allP<0.05).Fungi infection only occurred in L-VAP patients,the total antimicrobial resistance rate was 12.14% .Conclusion The prolongation of mechanical ventilation can increase the incidence of VAP,and resistance rate of pathogen in L-VAP is high.
2.Clinical study of UGT1A1 gene polymorphism in unconjugated hyperbilirubinemia after renal transplantation
Hang ZHAO ; Panxin PENG ; Zhenkai LUO ; Hailong LIU ; Xuming WANG ; Zhihao YANG
Chinese Journal of Organ Transplantation 2020;41(7):398-402
Objective:To explore the gene mutations of UGT1A1 * 6 and UGT1A1 * 28 in patients with unconjugated hyperbilirubinemia after renal transplantation and understand their clinical significance.Methods:UGT1A1*6 and UGT1A1*28 gene fragments in blood samples of patients with unconjugated hyperbilirubinemia after renal transplantation were detected by digital fluorescent molecular hybridization sequencing.Results:A total of 21 patients with unconjugated hyperbilirubinemia after renal transplantation were examined for UGT1A1*6 and UGT1A1*28 alleles. The results showed that there were 3 UGT1A1*28 and UGT1A1*6 combined heterozygous mutations, 4 UGT1A1*28 gene heterozygous mutations, 2 UGT1A1*6 heterozygous mutations and 4 UGT1A1*6 homozygous mutations. Among them, the mutation rates of UGT1A1*28 gene and UGT1A1*6 gene were 33%(7/21) and 43%(9/21) respectively and the total mutation rate of both was 62%(13/21).Conclusions:UGT1A1 polymorphism is associated with unconjugated hyperbilirubinemiaafter renal transplantation. By detecting the sequence of UGT1A1*6 and UGT1A1*28 gene fragments in blood samples of renal transplant patients, it is helpful to clarify the etiology of unconjugated hyperbilirubinemia after renal transplantation to confirm the diagnosis of Gilbert syndrome and rule out the effect of immunosuppressive drugs on liver function so as to guide the clinical medication of renal transplant patients.
3.Single-cell profiling of the copy-number heterogeneity in colorectal cancer
Shiyu SONG ; Lin FENG ; Kexing XI ; Zhigang SUN ; Deyang KONG ; Zhenkai LUO ; Wei PEI ; Haizeng ZHANG
Chinese Medical Journal 2023;136(6):707-718
Background::With functionally heterogeneous cells, tumors comprise a complex ecosystem to promote tumor adaptability and evolution under strong selective pressure from the given microenvironment. Diversifying tumor cells or intra-tumor heterogeneity is essential for tumor growth, invasion, and immune evasion. However, no reliable method to classify tumor cell subtypes is yet available. In this study, we introduced the single-cell sequencing combined with copy number characteristics to identify the types of tumor cells in microsatellite stable (MSS) colorectal cancer (CRC).Methods::To characterize the somatic copy number alteration (SCNA) of MSS CRC in a single cell profile, we analyzed 26 tissue samples from 19 Korean patients (GSE132465, the Samsung Medical Center [SMC] dataset) and then verified our findings with 15 tissue samples from five Belgian patients (GSE144735, the Katholieke Universiteit Leuven 3 [KUL3] dataset). The Cancer Genome Atlas (TCGA) cohort, GSE39582 cohort, and National Cancer Center (NCC) cohort (24 MSS CRC patients were enrolled in this study between March 2017 and October 2017) were used to validate the clinical features of prognostic signatures.Results::We employed single cell RNA-sequencing data to identify three types of tumor cells in MSS CRC by their SCNA characteristics. Among these three types of tumor cells, C1 and C3 had a higher SCNA burden; C1 had significant chromosome 13 and 20 amplification, whereas C3 was the polar opposite of C1, which exhibited deletion in chromosome 13 and 20. The three types of tumor cells exhibited various functions in the tumor microenvironment and harbored different mutations. C1 and C2 were linked to the immune response and hypoxia, respectively, while C3 was critical for cell adhesion activity and tumor angiogenesis. Additionally, one gene ( OLFM4) was identified as epithelium-specific biomarker of better prognosis of CRC (TCGA cohort: P = 0.0110; GSE39582 cohort: P= 0.0098; NCC cohort: P= 0.0360). Conclusions::On the basis of copy number characteristics, we illustrated tumor heterogeneity in MSS CRC and identified three types of tumor cells with distinct roles in tumor microenvironment. By understanding heterogeneity in the intricate tumor microenvironment, we gained an insight into the mechanisms of tumor evolution, which may support the development of therapeutic strategies.