AIM: To compare the efficacy and safety of tigecycline with polymyxin B in the treatment of carbapenem resistant enterobacteriaceae (CRE) pneumonia in critically ill patients. METHODS: A retrospective analysis was performed on the clinical data of patients with CRE pneumonia who received tigecycline or polymyxin B therapy from January 1, 2018 to Jun 30, 2023 in the Intensive Care Unit (ICU). Primary outcomes included the 28-day all-cause mortality and clinical cure rate within 28days. Secondary outcomes included the ICU mortality, in-hospital mortality, the length of hospital stay and ICU stay, microbial eradication, duration of mechanical ventilation. Independent predictors affecting 28-day clinical cure rate were tested using Cox regression analyses. RESULTS: A total of 83 eligible patients were included in the final analysis after propensity score matching, 54 in the tigecycline group and 29 in the polymyxin B group. The 28-day all-cause mortality was 31.5% (17/54) in the tigecycline group and 37.9% (11/29) in the polymyxin B group, the difference was not statistically significant (P=0.554); the clinical cure rate was 63% (34/ 54) in the tigecycline group, which was significantly higher than that of the polymyxin B group of 34.5% (10/29) (P = 0.013). There were no statistical differences between the two groups in terms of secondary outcomes. Multivariate logistic regression analysis found that the use of tigecycline was an independent predictor of the 28-day clinical cure rate (HR 2.083, 95%CI 1.018-4.263, P = 0.045). However, activated partial thromboplastin time (APTT) and prothrombin time (PT) were significantly prolonged in the tigecycline group compared with the polymyxin B group (P=0.047; P=0.027), and fibrinogen (FIB) was significantly decreased (P < 0.001) after drug administration. CONCLUSION: There was no significant difference in 28-day all-cause mortality between the tigecycline and polymyxin groups; tigecycline might be associated with a higher 28-day clinical cure rate compared with polymyxin B. It should be noted that tigecycline may increase the risk of coagulation abnormalities.

BACKGROUND:As a routine method after lumbar spine surgery,a drainage tube is convenient for postoperative bleeding drainage and management,and there is still no consensus on the choice of postoperative removal time for short-segment lumbar spine surgery with less risk. OBJECTIVE:To explore the effect of different drainage times on early clinical efficacy after short-segment lumbar fusion. METHODS:A prospective randomized controlled study was performed on 220 patients in the Affiliated Hospital of Southwest Medical University who underwent posterior lumbar interbody fusion for lumbar degenerative diseases from March 2017 to April 2021.According to the different drainage times,the patients were randomly divided into removal on the second day after operation(group A),removal on the third day after operation(group B),and removal after the observation method 24-hour drainage volume<30 mL(group C).The perioperative indicators and follow-up results of the three groups of patients were observed and compared. RESULTS AND CONCLUSION:(1)Because 7 patients were lost to follow-up,2 patients were excluded,and 211 patients were finally included(72 patients in group A,71 patients in group B,and 68 patients in group C).(2)The average drainage time of group C was 2.91 days.The postoperative drainage volume in group A was significantly less than that in groups B and C,and the difference was statistically significant(P<0.05).On day 3 after operation,the hematocrit value of group C was lower than that of group A and group B,and the difference was statistically significant(P<0.05).Postoperative activity time and hospital stay in group A were shorter than those in groups B and C,and the difference was statistically significant(P<0.05).(3)Four patients in group A,two patients in group B and three patients in group C received an allogeneic blood transfusion.There was no significant difference among the groups(P>0.05).(4)In terms of postoperative complications,there were no statistical differences in postoperative wound leakage and surgical site infection in all three groups(P>0.05).(5)All patients were followed up for more than 12 months.Visual analog scale score and Oswestry dysfunction index of the three groups of patients before discharge and at the last follow-up were significantly improved compared with those before surgery(P<0.05).There was no statistical significance among the groups(P>0.05).(6)It is indicated that the removal of the drainage tube on the second day after a posterior lumbar fusion can effectively reduce the time to get out of bed and hospital stay,without increasing the postoperative blood loss and the risk of complications.

AIM:To investigate the pharmacoki-netic/pharmacodynamic(PK/PD)profile of esome-prazole for injection in critically ill patients.METH-ODS:This was a prospective,single-center,open-la-bel study,all patients received intravenous infused esomeprazole 40 mg q12h for stress ulcer prophy-laxis,treatment duration is determined by clini-cians based on patients condition.Forty critically ill patients were enrolled and were divided into single and multiple dose groups according to the timing of blood sample collection.Twenty-one patients in the single-dose group had their blood samples col-lected at 1,3,6,8,and 12 h after the first dose,and 34 patients in the multiple-dose group had their blood samples collected at 0 h before the fifth dose and 1,3,6,and 8,and 12 h after the fifth dose,of which 14 patients had their blood samples collected at both the first dose and the repeated doses.The concentration of esomeprazole was measured by HPLC-MS/MS,and PK parameters were analyzed using noncompartmental analysis.Gastric aspirates were collected for pH measure-ment in fasted patients with gastric tube before the first dose(0 h),and 1,2,4,8,12,14,16,20,24 h after the initiation of drug administration,and the percentage of time with pH≥4 was calculated.All adverse events and serious adverse events during treatment were recorded.RESULTS:Patients in the single-dose group were 67.75 years old(45-69 years)with a BMI(24.05±3.35)kg/m2,and pa-tients in the multiple-dose group were 63.35 years old(24-87 years)with a BMI(24.08±3.29)kg/m2.PK parameters after the first dose were AUC0-t(11.26±6.58)mg·h·L-1,Cmax(3.08±2.06)mg/L,CL(4.13±3.68)L/h,Vd(17.12±6.13)L,t1/2(4.80±3.06)h;PK parameters after multiple doses were AUC0-t(16.70±11.20)mg·h/L,Cmax(3.37±2.59)mg/L,CL(3.94±2.94)L/h,Vd(22.71±17.26)L,t1/2(5.23±3.34)h.Percentage of time with pH≥4 with-in 0 h-24 h after administration was 61.69％,and percentage of time with pH≥4 within 12 h-24 h was up to 100％.Esomeprazole was well tolerated by all patients with no serious adverse events.CONCLU-SION:Compared with healthy volunteers,inject-able esomeprazole showed increased Vd,decreased CL,increased drug exposure and accumulation af-ter repeated administration in critically ill patients.The drug had a favorable safety profile in critically ill patients.

This study investigated the choroplast genome sequence of wild Atractylodes lancea from Yuexi in Anhui province by high-throughput sequencing, followed by characterization of the genome structure, which laid a foundation for the species identification, analysis of genetic diversity, and resource conservation of A. lancea. To be specific, the total genomic DNA was extracted from the leaves of A. lancea with the improved CTAB method. The chloroplast genome of A. lancea was sequenced by the high-throughput sequencing technology, followed by assembling by metaSPAdes and annotation by CPGAVAS2. Bioiformatics methods were employed for the analysis of simple sequence repeats(SSRs), inverted repeat(IR) border, codon bias, and phylogeny. The results showed that the whole chloroplast genome of A. lancea was 153 178 bp, with an 84 226 bp large single copy(LSC) and a 18 658 bp small single copy(SSC) separated by a pair of IRs(25 147 bp). The genome had the GC content of 37.7% and 124 genes: 87 protein-coding genes, 8 rRNA genes, and 29 tRNA genes. It had 26 287 codons and encoded 20 amino acids. Phylogenetic analysis showed that Atractylodes species clustered into one clade and that A. lancea had close genetic relationship with A. koreana. This study established a method for sequencing the chloroplast genome of A. lancea and enriched the genetic resources of Compositae. The findings are expected to lay a foundation for species identification, analysis of genetic diversity, and resource conservation of A. lancea.
Phylogeny ; Atractylodes/genetics* ; Genome, Chloroplast ; Whole Genome Sequencing ; Microsatellite Repeats ; Lamiales

4-(Cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase (CMK) was one of the key enzymes in the methylerythritol-4-phosphate (MEP) pathway to generate terpenoids. In this study, based on the transcriptome data of Atractylodes lancea, the sequence of the CMK gene was cloned, named AlCMK (GenBank accession number OM283293). The results showed that AlCMK contains a 1 230 bp open reading frame (ORF) encoding 409 amino acids. The deduced protein had a theoretical molecular weight of 44 752.53 and an isoelectric point of 6.67. Transmembrane structure analysis showed that there was no transmembrane structure, and the secondary structure of AlCMK was predicted to be mainly composed of random coil. Homologous alignment revealed that AlCMK shared high sequence identity with the CMK proteins of Tanacetum cinerariifolium, Osmanthus fragrans, Eucommia ulmoides, Lonicera japonica and Salvia miltiorrhiza. Phylogenetic analysis indicated that AlCMK protein had the higher homology with CMK protein of Compositae. The pET-32a-AlCMK prokaryotic expression vector was constructed and a fusion protein with molecular mass of about 65 kDa was expressed in the E. coli BL21 (DE3). The qRT-PCR was used to analyze the expression pattern of AlCMK gene in different tissues and after MeJA treatment. Meanwhile, the enzyme activity was determined by ELISA kit. The results showed that AlCMK gene was tissue-expressed in different origins and its expression was induced by MeJA, and the results of the enzyme activity assay showed that the AlCMK enzyme activity in different regions was higher in the leaves. The subcellular localization showed that AlCMK was located in the chloroplast. This study provides a reference for further elucidating the biological function of AlCMK gene in terpenoid synthesis pathway in Atractylodes lancea.

OBJECTIVE: To analyze the changes in the gene expression profile of T cells in CML patients after TCRζ up-regulation expression, and to explore the molecular mechanism of T cell reactivation after transgenic up-regulation of TCRζ. METHODS: The peripheral blood mononuclear cells(PBMCs) from 3 newly untreated chronic-stage CML patients were collected, and the CD3 RESULTS: A total of 2248 differentially-expressed genes were obtained, including 553 up-regulated genes and 1695 down-regulated genes in experimental group as compared with those in control group (P<0.05) . The GO and KEGG enrichment analyses showed that differentially expressed genes involved in the biological processes related to T cell immune function, such as TCR signaling pathway, T cell proliferation and activation. Some of core genes involved in promoting the TCR signaling pathway, T cell proliferation, activation and apoptosis pathways were significantly up-regulated, while some core genes involved in inhibiting T cell activation were significantly down-regulated. CONCLUSION The molecular mechanism of the significantly improved T cell activation and proliferation ability in CML patients after TCRζ up-regulation may be related to the differential transcripts mediated signaling pathways of T cell activation, proliferation and apoptosis.
Humans ; Leukocytes, Mononuclear ; Lymphocyte Activation ; Receptors, Antigen, T-Cell/genetics* ; T-Lymphocytes ; Up-Regulation

In this study, the gene encoding the key enzyme 3-ketoacyl-CoA thiolase(KAT) in the fatty acid β-oxidation pathway of Atractylodes lancea was cloned. Meanwhile, bioinformatics analysis, prokaryotic expression and gene expression analysis were carried out, which laid a foundation for the study of fatty acid β-oxidation mechanism of A. lancea. The full-length sequence of the gene was cloned by RT-PCR with the specific primers designed according to the sequence information of KAT gene in the transcriptomic data of A. lancea and designated as AIKAT(GenBank accession number MW665111). The results showed that the open reading frame(ORF) of AIKAT was 1 323 bp, encoding 440 amino acid. The deduced protein had a theoretical molecular weight of 46 344.36 and an isoelectric point of 8.92. AIKAT was predicted to be a stable alkaline protein without transmembrane segment. The secondary structure of AIKAT was predicted to be mainly composed of α-helix. The tertiary structure of AIKAT protein was predicted by homology modeling method. Homologous alignment revealed that AIKAT shared high sequence identity with the KAT proteins(AaKAT2, CcKAT2, RgKAT and AtKAT, respectively) of Artemisia annua, Cynara cardunculus var. scolymus, Rehmannia glutinosa and Arabidopsis thaliana. The phylogenetic analysis showed that AIKAT clustered with CcKAT2, confirming the homology of 3-ketoacyl-CoA thiolase genes in Compositae. The prokaryotic expression vector pET-32 a-AIKAT was constructed and transformed into Escherichia coli BL21(DE3) for protein expression. The target protein was successfully expressed as a soluble protein of about 64 kDa. A real-time quantitative PCR analysis was performed to profile the AIKAT expression in different tissues of A. lancea. The results demonstrated that the expression level of AIKAT was the highest in rhizome, followed by that in leaves and stems. In this study, the full-length cDNA of AIKAT was cloned and expressed in E. coli BL21(DE3), and qRT-PCR showed the differential expression of this gene in different tissues, which laid a foundation for further research on the molecular mechanism of fatty acid β-oxidation in A. lancea.
Amino Acid Sequence ; Atractylodes/genetics* ; Cloning, Molecular ; Coenzyme A ; Escherichia coli/genetics* ; Phylogeny

italic>Crataegus pinnatifida is a traditional Chinese medicine, which contains organic acids, triterpenoid acids and other active components, has important medicinal and edible value. In order to study the difference of gene expression level in different developmental stages of hawthorn and explore the genes of active ingredient biosynthesis in Crataegus pinnatifida, high-throughput Illumina HiSeq 2000 technology were used to conduct transcriptome sequencing and bioinformatics analysis on Crataegus pinnatifida fruits from the same origin at different developmental stages. 78 496 Unigenes with an average length of 941 nt were obtained by Trinity software. Among them, 58 395 Unigenes can be annotated by NR, NT, Swiss prot, KEGG, COG, GO and other public databases. KEGG pathway analysis showed that 52 Unigenes encoding 15 key enzymes involved in the citric acid cycle. There are 62 Unigenes were involved in the triterpene biosynthesis pathway of Crataegus pinnatifida. Two key enzymes SQE of triterpenoid metabolism pathway in Crataegus pinnatifida were cloned and performed bioinformatic analysis. The results showed that ORF of CpSQE1 and CpSQE2 were 1 594 bp and 1 597 bp, respectively, encoding 530 and 531 amino acids. The molecular weight of proteins was 57.6 kDa and 57.5 kDa. Bioinformatics analysis showed that both CpSQE1 and CpSQE2 proteins have a PLN02985 superfamily conserved domain, belonging to the squalene monooxygenase superfamily. The phylogenetic tree shows that CpSQE1 and CpSQE2 are clustered together with SQE with squalene epoxidase function in other plants. This study provides a research basis for further exploring the key genes in the biosynthesis process of hawthorn active ingredients and analyzing the regulation pathway of its active ingredient biosynthesis.

Objective:To explore the effect of combined administration of intravenous and topical tranexamic acid on perioperative blood loss in elbow arthrolysis.Methods:A retrospective analysis was conducted of 31 patients who had undergone elbow arthrolysis due to elbow stiffness from April 2019 to November 2020 at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital. An observational group of 15 patients were subjected to combined administration of intravenous and topical tranexamic acid while a control group of 16 patients to no administration of tranexamic acid. In the observational group, 15 mg/kg of tranexamic acid was injected intravenously 5 to 10 minutes before surgery and 1.0 g of tranexamic acid was injected locally in the area of anterior and posterior joint capsules after incision was closed while drainage tubes were clamped for 2 hours before release. In the control group, there was no special operative procedure while drainage tubes were also clamped for 2 hours before release. The 2 groups were compared in terms of blood loss on day 1 and day 3 after operation, drainage volume on day 1 after operation, total drainage volume, time for indwelling drainage tube, complications, and Mayo elbow performance score (MEPS) at 3 months after operation.Results:There were no statistically significant difference in preoperative general data between the 2 groups, showing they were comparable ( P>0.05).On day 1 and day 3 after operation, the blood loss was respectively (533.4±318.3) mL and (792.0±375.6) mL in the observational group, and respectively (866.4±480.5) mL and (1,403.0±636.5) mL in the control group, showing significantly differences between the 2 groups ( P<0.05). The drainage volume on day 1 after operation was (151.3±90.1) mL in the observational group and (235.0±126.1) mL in the control group, showing a significant difference between the 2 groups ( P<0.05). There was no statistically significant difference in total drainage volume or time for indwelling drainage tube between the 2 groups ( P>0.05). There were no such complications as thromboembolic events in either group. There was no significant difference in MEPS between the 2 groups at 3 months after operation ( P>0.05). Conclusions:Combined administration of intravenous 15 mg/kg and topical 1.0 g tranexamic acid may reduce blood loss on day 1 and day 3 after operation and drainage volume on day 1 after operation, and may not increase the risk of thromboembolic events, but cannot reduce total drainage volume or time for indwelling drainage tube. Application of tranexamic acid may not affect early elbow joint function after operation.

OBJECTIVE: To investigate the expression and clinical significance of PD-L1 and microRNA-138-5p in the peripheral blood mononuclear cells of patients with acute myeloid leukemia. METHODS: The SYBR GreenⅠreal-time PCR was used to detect the expression levels of PD-L1 mRNA and miR-138 in 20 cases of primary AML, 9 cases of relapsed/refractory AML and 8 cases of complete remission. The samples of peripheral blood of 20 healthy peoples were used as controls. RESULTS: The expression levels of PD-L1 in both the primary AML and the relapsed/refractory AML groups were significantly higher than those in the healthy control group (P<0.01), and the expression level of PD-L1 in the relapsed/refractory AML group was significantly higher than that in the primary AML group (P<0.01). The expression level of miR-138 in both the primary AML and the relapsed/refractory AML groups were significantly lower than that in the healthy control group (P<0.01). The 8 sampes out of 20 cases of primary AML patients achieved complete remission (CR) were collected and detected. The results showed that the expression level of miR-138 in the complete remission group was higher than that in the primary AML group (P<0.05), but the expression level of PD-L1 mRNA in the CR group was not significantly different from that in the primary AML group (P>0.05). and there was a negative correlation between PD-L1 mRNA and miR-138 in primary AML patients (P<0.05). CONCLUSION The expression of PD-L1 increases and the expression of miR-138 down-regulates in PBMNCs of AML patients, furthermore, both correlate each other.
B7-H1 Antigen ; genetics ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Leukocytes, Mononuclear ; MicroRNAs ; genetics ; Remission Induction