An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

CCDC50, an essential driver involved in tumorigenesis, is a potential severity marker of diffuse large B cell lymphoma.

Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of blood cancer. Among the subtypes, the activated B-cell (ABC) subtype is typically more aggressive and associated with worse outcomes. However, the underlying mechanisms are not fully understood. In this study, we performed microarray analysis to identify potential ABC-DLBCL-associated genes. We employed Kaplan-Meier methods and cox univariate analysis to explore the prognostic value of the identified candidate gene Coiled-coil domain containing 50 (CCDC50). Additionally, we used DLBCL cell lines and mouse models to explore the functions and mechanisms of CCDC50. Finally, we isolated CCDC50-bearing exosomes from clinical patients to study the correlation between these exosomes and disease severity. Our results demonstrated that CCDC50 not only showed significantly positive correlations with ABC subtype, tumor stage and number of extranodal sites, but also suggested poor outcomes in DLBCL patients. We further found that CCDC50 promoted ABC-DLBCL proliferation in vitro and in vivo. Mechanistically, CCDC50 inhibited ubiquitination-mediated c-Myc degradation by stimulating the PI3K/AKT/GSK-3ß pathway. Moreover, CCDC50 expression was positively correlated with c-Myc at protein levels in DLBCL patients. Additionally, in two clinical cohorts, the plasma CCDC50-positive exosomes differentiated DLBCL subtypes robustly (AUC > 0.80) and predicted disease severity effectively (p < 0.05). Our findings suggest that CCDC50 likely drives disease progression in ABC-DLBCL patients, and the CCDC50-bearing exosome holds great potential as a non-invasive biomarker for subtype diagnosis and prognosis prediction of DLBCL patients.

Anti-N-methyl-D-aspartate receptor encephalitis: a prospective study focused on cerebrospinal fluid and clinical symptoms.

BACKGROUND AND OBJECTIVE: To analyze the relationship between brain MRI, clinical symptoms, and cerebrospinal fluid (CSF) and to provide a reference for early diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. MATERIALS AND METHODS: A total of 62 patients with anti-NMDAR encephalitis in Zhengzhou, China (2016-2018) were observed and registered prospectively. First, we analyzed the characteristics of clinical symptoms. Second, according to the disease duration, patients were divided into two groups, and then we analyzed the CSF features. In addition, they were divided into two groups according to the brain MRI, and then the CSF features were analyzed. Finally, the characteristics of cerebrospinal fluid in patients with seizure as the initial symptom were analyzed. RESULTS: Seizure presents as the initial symptom in 14 patients (22.5%), including 11 males (78.57%). The proportion and concentration of CSF total protein abnormalities in the early stage group were significantly higher than those in the middle and late group (P < 0.05). The total protein concentration in the abnormal brain MRI group was significantly higher than that in the normal MRI group (P < 0.05). CONCLUSION: Anti-NMDAR encephalitis should be suspected, when male patients complain of seizure as an initial symptom and have simultaneously had headaches or fever prior to onset. The sensitivity of anti-NMDAR antibody is higher in CSF than in serum. Total CSF protein is more prone to elevation in the middle and late stages of anti-NMDAR encephalitis. Brain MRI abnormalities with anti-NMDAR encephalitis are related to the total protein concentration of CSF, which may be related to the disease duration.

Wilms' tumor 1-associating protein plays an aggressive role in diffuse large B-cell lymphoma and forms a complex with BCL6 via Hsp90.

BACKGROUND: Wilms' tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear. METHODS: Immunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation. RESULTS: WTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro. CONCLUSION: WTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL.

Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis.

CONTEXT: Association between inherited variants and the risks of sepsis is controversial. OBJECTIVE: To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10. MATERIALS AND METHODS: Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls. RESULTS: Subjects with IL-10 -1082 AA genotypes and IL-6 -174 CC genotype had a higher risk of sepsis and increased mRNA levels. CONCLUSION: The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.

KIF23 is a potential biomarker of diffuse large B cell lymphoma: Analysis based on bioinformatics and immunohistochemistry.

ABSTRACT: Diffuse Large B Cell Lymphoma (DLBCL), the most common form of blood cancer. The genetic and clinical heterogeneity of DLBCL poses a major barrier to diagnosis and treatment. Hence, we aim to identify potential biomarkers for DLBCL.Differentially expressed genes were screened between DLBCL and the corresponding normal tissues. Kyoto Encyclopedia of Genes and Genomes and Gene oncology analyses were performed to obtain an insight into these differentially expressed genes. PPI network was constructed to identify hub genes. survival analysis was applied to evaluate the prognostic value of those hub genes. DNA methylation analysis was implemented to explore the epigenetic dysregulation of genes in DLBCL.In this study, Kinesin family member 23 (KIF23) showed higher expression in DLBCL and was identified as a risk factor in DLBCL. The immunohistochemistry experiment further confirmed this finding. Subsequently, the univariate and multivariate analysis indicated that KIF23 might be an independent adverse factor in DLBCL. Upregulation of KIF23 might be a risk factor for the overall survival of patients who received an R-CHOP regimen, in late-stage, whatever with or without extranodal sites. Higher expression of KIF23 also significantly reduced 3, 5, 10-year overall survival. Furthermore, functional enrichment analyses (Kyoto Encyclopedia of Genes and Genomes, Gene oncology, and Gene Set Enrichment Analysis) showed that KIF23 was mainly involved in cell cycle, nuclear division, PI3K/AKT/mTOR, TGF-beta, and Wnt/beta-catenin pathway in DLBCL. Finally, results of DNA methylation analysis indicated that hypomethylation in KIF23's promoter region might be the result of its higher expression in DLBCL.The findings of this study suggested that KIF23 is a potential biomarker for the diagnosis and prognosis of DLBCL. However, further studies were needed to validate these findings.

NEK2 Promotes Cell Proliferation and Glycolysis by Regulating PKM2 Abundance via Phosphorylation in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent and commonly diagnosed subtype of NHL, which is characterized by high heterogeneity and malignancy, and most DLBCL patients are at advanced stages. The serine/threonine kinase NEK2 (NIMA-related kinase 2), a member of NIMA-related kinase (NEK) family that regulates cell cycle, is upregulated in a variety of malignancies, including diffuse large B-cell lymphoma. However, the role and underlying mechanisms of NEK2 in DLBCL have seldom been discussed. In this study, we identified that NEK2 is upregulated in DLBCL compared to normal lymphoid tissues, and overexpression of NEK2 predicted a worse prognosis of DLBCL patients. Gene set enrichment analysis indicates that NEK2 might participate in regulating glycolysis. Knockdown of NEK2 inhibited growth and glycolysis of DLBCL cells. The interaction between NEK2 and PKM2 was discovered by tandem affinity purification and then was confirmed by immunofluorescence staining, coimmunoprecipitation, and immunoprecipitation. NEK2 bounds to PKM2 and regulates PKM2 abundance via phosphorylation, which increases PKM2 stability. The xenograft tumor model checks the influence of NEK2 on tumor growth in vivo. Thus, NEK2 could be the novel biomarker and target of DLBCL, which remarkably ameliorates the diagnosis and treatment of DLBCL.

[Research progress on prognostic markers of chronic lymphocytic leukemia].

Chronic lymphocytic leukemia (CLL) remains the most common adult leukemia. The recent progress on research of molecular and cellular genetics of CLL promotes the development of the diagnosis, treatment and prognosis for CLL patients. IGVH gene mutation status is the most important prognostic marker for CLL patients. Zeta-chain-associated protein kinase (ZAP-70) can be used as a surrogate marker for IGVH mutation status. CD38 is a type II transmembrane glycoprotein promoting B cell activation and proliferation, which can improve the survival of CLL cells and enhance their proliferation, so it also can be used as an independent prognostic indicator for CLL. Chromosome aberrations are found in more than 80% of CLL cases. The most frequent abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common. The most common gains of chromosomal material are trisomies 12q. Human leukocyte antigen G (HLA-G) is a non-classical HLA-I gene. Increased expression of HLA-G leads to the malignant progression of CLL, significantly shortens survival, indicating HLA-G might serve as a prognostic marker in CLL. Toll-like receptors (TLA) are important component of natural immunity. The combination of TLR agonists and release chemotherapy, monoclonal antibodies and tumor vaccines would bring a breakthrough for the treatment of CLL.

[Risk factors for death and their predictive value on diabetic kidney disease patients in intensive care unit based on MIMIC-III database].

OBJECTIVE: To analyze the influencing factors of prognosis of patients with diabetic kidney disease (DKD) in intensive care unit (ICU), and analyze their predictive value. METHODS: Based on the inpatient information of more than 50 000 patients from June 2001 to October 2012 in the latest version of American Intensive Care Medical Information Database (MIMIC-III v1.4), the data of DKD patients were screened out, including gender, age, body weight, comorbidities [hypertension, coronary heart disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD)], sequential organ failure assessment (SOFA) score, the length of ICU stay, the incidence of mechanical ventilation, vasoactive drugs and renal replacement therapy during the ICU hospitalization, complications of other diseases [ventilator-associated pneumonia (VAP), urinary tract infection (UTI), diabetic ketoacidosis (DKA), acute myocardial infarction (AKI)] and prognosis of ICU. At the same time, the blood routine and biochemical data of the first 24 hours in ICU and the extremum values during the ICU hospitalization were collected. Multivariate Logistic regression analysis was used to screen the prognostic factors of DKD patients in ICU, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of death risk factors. RESULTS: 416 DKD patients were screened out, 20 patients were excluded due to data missing, and finally 396 patients were enrolled, including 220 survival patients and 176 dead patients. Compared with the survival group, the patients in the death group were older (years old: 57.13±13.04 vs. 52.61±14.15), with lower rates of hypertension and CKD (11.4% vs. 23.6%, 26.7% vs. 41.4%), higher SOFA scores and baseline values of blood urea nitrogen (BUN), serum creatinine (SCr) and blood K+ [SOFA score: 5.86±2.79 vs. 4.49±2.56, BUN (mmol/L): 18.4±10.0 vs. 14.8±9.0, SCr (µmol/L): 387.2±382.8 vs. 284.6±244.9, K+ (mmol/L): 4.64±0.99 vs. 4.33±0.86], and longer ICU stay [days: 2.65 (1.48, 5.21) vs. 2.00 (1.00, 4.00)], and the differences were statistically significant (all P < 0.01). Further analysis of laboratory tests extremum values during ICU hospitalization showed that the maximum (max) and minimum (min) values of white blood cell (WBC), BUN and SCr, and K+max in the death group were significantly higher than those in the survival group [WBCmax (×109/L): 17.3±10.3 vs. 14.5±7.3, WBCmin (×109/L): 7.9±4.1 vs. 6.7±2.7, BUNmax (mmol/L): 23.8±10.4 vs. 18.8±10.2, BUNmin (mmol/L): 11.0±6.6 vs. 9.3±6.6, SCrmax (µmol/L): 459.7±392.5 vs. 350.1±294.4, SCrmin (µmol/L): 246.6±180.3 vs. 206.9±195.4, K+max (mmol/L): 5.35±0.93 vs. 5.09±0.99], and the minimum values of hemoglobin (Hbmin) and glucose (Glumin) were significantly lower than those in the survival group [Hbmin (g/L): 87.4±14.5 vs. 90.6±16.5, Glumin (mmol/L): 4.0±1.7 vs. 4.6±2.0], and the differences were statistically significant (all P < 0.05). The incidences of mechanical ventilation and vasoactive drugs during ICU hospitalization in the death group were significantly higher than those in the survival group (37.5% vs. 24.1%, 32.4% vs. 20.0%, both P < 0.01), and the incidences of UTI and AMI in the death group were significantly higher than those in the survival group (29.5% vs. 19.1%, 8.5% vs. 3.6%, both P < 0.05). Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.019, 95% confidence interval (95%CI) was 1.003-1.036, P = 0.023], SOFA score (OR = 1.142, 95%CI was 1.105-1.246, P = 0.003), WBCmin (OR = 1.134, 95%CI was 1.054-1.221, P = 0.001) and BUNmax (OR = 1.010, 95%CI was 1.002-1.018, P = 0.018) were risk factors of death of DKD patients in ICU. ROC curve analysis showed that the area under ROC curve (AUC) of combination of risks factors of death was 0.706, the sensitivity was 61.6%, and the specificity was 73.2%. CONCLUSIONS: In order to prevent DKD patients from getting worse in ICU, we should pay close attention to the blood biochemical indexes, especially the renal function indexes, and give timely treatment. At the same time, we should actively prevent the occurrence of complications such as infection and cardiovascular disease.

Rare occurrence of IgVH gene translocations and restricted IgVH gene repertoire in ocular MALT-type lymphoma.

FISH studies on 37 ocular MALT-type lymphomas yielded chromosomal translocations affecting MAL andT1 BCL10 in 1 case each, no evidence for a break in the FOXP1 locus, and trisomy 3 in 14 out of 34 cases (41%). Three out of 8 cases analyzed used the highly mutated VH3-23 gene and showed ongoing somatic hypermutations.

[Clonality analysis and mutation status of IgVH genes in classic Richter's syndrome].

OBJECTIVE: To study the clonal rearrangements and mutation status of IgVH genes in classic Richter's syndrome, the relationship between molecular findings of IgVH gene and clinical outcome, and to deciper the possible molecular mechanism of transformation. METHODS: The clonal rearrangements and mutation status of IgVH genes were analyzed in cases of classic Richter's syndrome by Genescan and sequencing. Immunohistochemical study for zeta-chain associated protein kinase 70 kDa (ZAP70), p53 and interferon regulation factor 4 (IRF-4) was also performed. RESULTS: Samples of 18 cases of B-chronic lymphocytic leukemia (B-CLL)/ diffuse large B-cell lymphoma (DLBCL,78. 3%) had identical tumor cell clones, whereas DLBCL developed as a clonally independent neoplasm in 5 patients (21.7%). Among the clonally related group, 12 cases carried unmutated VH genes in both B-CLL and DLBCL components and VH3-23, VH3-74 and VH1-2 were accounted for the B-CLL transformation to DLBCL. Immunohistochemical study showed that the transformed DLBCL expressed CD5 in 32.1% of cases, CD23 in 14.3%, ZAP70 in 23.8%, p53 in 80.6% and IRF-4 in 82.6% of the cases respectively. Follow-up data were available in 17 patients with classic Richter's syndrome. The median survival period was 7 months. No significant difference in survival rate was obtained between the clonally related or unrelated groups, between IgVH gene mutated or unmutated groups, and between the groups with or without expression of ZAP70, p53 and IRF-4. CONCLUSIONS: The ratio of clonally related transformed DLBCL from B-CLL to clonally unrelated DLBCL is 2:1. Clonal transformation to DLBCL predominantly occurs in B-CLL patients carrying unmutated IgVH genes. The biased IgVH gene usage suggests antigens are involved in classic Richter's syndrome. Molecular differences of IgVH genes and very poor clinical outcome of this group of transformed DLBCL indicate that there cases may be regarded as a distinct subset of DLBCL.

[Clonality analysis and mutational status of IgVH gene in Hodgkin variant of Richter syndrome].

OBJECTIVE: To detect the clonal relationship, the rearrangement, and the mutational status of IgVH gene; the influence of these molecular characteristics on the clinical outcome in Hodgkin variant of Richter syndrome; and the possible molecular pathogenesis in this transformation. METHODS: The clonal rearrangements and mutational status of IgVH genes were analyzed in Hodgkin variant of Richter syndrome and B-CLL with Reed-Stemberg (R-S)-like cells by GeneScan analysis and sequencing. Semi-nest PCR based on laser capture microdissection was utilized to compare the clonal relationship between B-CLL and R-S/R-Slike cells. Immunohistochemical staining was used to detect the different expressions of ZAP70, p53, IRF-4 and LMP1 in the two components. RESULTS: (1) 5/6 B-CLL cases transformed to Hodgkin lymphoma (HL)/R-S-like cells carried the mutated IgVH genes; (2) 2 cases of R-S cells and 1 case of R-S-like cells were clonally distinct from B-CLL clone and express LMP1, whereas 1 case of R-S-like cells was relating to the surrounding B-CLL cells and did not express LMP1; (3) 2/6 B-CLL cases transformed to HL convey VH4-34 and VH3-48 respectively. CONCLUSIONS: (1) Richter transformation to HL/R-S-like cells evolves from the B-CLL which originates from the germinal center or post germinal center B cells, indicating that different lymphoma cells of different subtypes in Richter syndrome come from different B cell lineage and possibly involve a different pathogenesis and pathway; (2) HL and R-S-like cells evolve from either the B-CLL clone or may develop as a clonally unrelated lymphoma, the independent secondary malignancies are appear to be EBV-positive, possibly as a consequence of the underlying immunodeficiency; (3) The biased usage of IgVH genes suggested a role of antigens involved in the HL variant of Richter syndrome.

IgVH mutational status and clonality analysis of Richter's transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 different pathways of disease evolution.

Approximately 5% of B-cell chronic lymphocytic leukemia (B-CLL) patients develop a secondary aggressive lymphoma, usually of diffuse large B-cell type (DLBCL), termed Richter's transformation (RT). Rarely, classic Hodgkin lymphoma (HL) is observed. Published small series suggest that tumor cells in DLBCL and HL can be clonally identical to the B-CLL clone or arise as an independent, secondary lymphoma. We describe the morphology, immunophenotype, and clinical features of 34 classic RT patients with DLBCL, 6 cases of B-CLL with HL, and 8 cases with scattered CD30-positive Hodgkin and Reed-Sternberg (HRS)-like cells. The clonal relationship of the 2 components was analyzed using sequencing analysis of immunoglobulin heavy chain variable region (IgVH) genes. In classic RT, 18/23 B-CLL cases (78%) showed clonal progression to DLBCL with identical IgVH sequences in both lymphoma components, whereas in 5 cases (22%) the DLBCL was clonally unrelated. Among clonally related RT samples, 73% carried unmutated IgVH genes, whereas 4/5 unrelated cases were mutated. Immunophenotypically, most cases of DLBCL irrespective of clonal relatedness showed significant differences in phenotype compared with the B-CLL, with common loss of CD5 and CD23. Using immuno-laser capture microdissection, sequencing of the IgVH CDR3 region of isolated HRS cells showed that 2/2 cases with HL were clonally unrelated, whereas they were clonally identical in 1/2 cases of B-CLL with scattered HRS-like cells. HRS or HRS-like cells in all 3 unrelated cases showed evidence of Epstein-Barr virus infection. Of interest, 5/6 cases of B-CLL with HL, and 5/6 cases of B-CLL with HRS cells showed mutated IgVH genes.

A novel microsatellite within intron 8 in caspase10 gene in Chinese of Han nationality.

OBJECTIVE: To investigate polymorphisms in the coding exons and their splicing areas of caspase10 gene (CASP10) in Chinese of Han nationality. METHODS: Polymerase chain reaction (PCR), denaturing high-performance liquid chromatography (DHPLC), direct sequencing and clonal sequencing were used to analyze the exon 9 and its flanking sequences. RESULTS: In 70 blood samples of Chinese subjects researched the known single nucleotide polymorphisms (SNPs) in the exon 9 of CASP10 gene published in dbSNP of NCBI were not identified. We found a short sequence with more than ten continuous and repeated T nucleotides within the intron 8 near the exon 9 and the length of repeated sequence nucleotides T was different in samples. Clonal sequencing analysis indicated that it was a microsatellite of single nucleotide-repeated sequence. The recurrence and specificity of same result was further confirmed by PCR with high fidelity polymerase and sequencing. Furthermore all of 70 blood samples detected by DHPLC showed heterozygous profiles. We named it as IVS8-13(T)n temperately. CONCLUSION: Our research suggested that the site be a microsatellite of single nucleotide-repeated sequence. Meanwhile, our data further showed that it was quite different from that by querying SNP database of non-Chinese population in NCBI, in the same region a SNP of type of insertion deletion existed. It could be inferred that the difference between the populations might be associated with the genetic characteristics of ethnics. The significance of the microsatellite in CASP10 gene in Chinese of Han nationality remains to be elucidated.

Effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome.

OBJECTIVE: To observe the effects of Xuanbai Chengqi decoction on lung compliance for patients with exogenous pulmonary acute respiratory distress syndrome. SUBJECTS AND METHODS: A total of 53 patients with exogenous pulmonary acute respiratory distress syndrome, who were admitted to the intensive care unit of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine from March 2009 to February 2013, were selected. They were randomly divided into the treatment group (25 cases) and the control group (28 cases). Both the groups were treated with conventional treatment and lung-protective ventilation strategy; apart from these, enema therapy with Xuanbai Chengqi decoction was given to the treatment group. Meanwhile, static lung compliance, dynamic lung compliance, peak airway pressure, plateau pressure, and positive end-expiratory pressure (PEEP) for patients in both the groups were observed and recorded at 24, 48, and 72 hours after the drug was used. Moreover, variations in the duration of parenteral nutrition, incidence rate of complications, and case fatality rate in patients after treatment were recorded. RESULTS: For patients in the treatment group, at 48 and 72 hours after treatment, the static lung compliance and dynamic lung compliance were significantly higher than those in the control group, while plateau pressure, peak airway pressure, and PEEP were significantly lower than those before treatment. At the same time, PEEP for patients in the treatment group at 72 hours after treatment was remarkably lower than that in the control group, showing significant difference (P<0.05). The duration of parenteral nutrition in the treatment group was significantly shorter than that in the control group (P<0.05). Both the incidence rate and the fatality rate of complications, such as abdominal distension and ventilator-associated pneumonia, for patients in the treatment group were distinctly smaller than those in the control group (P<0.05). CONCLUSION: Xuanbai Chengqi decoction not only can improve the static lung compliance and dynamic compliance of patients with exogenous pulmonary distress syndrome but also can shorten the parenteral nutrition duration, as well as reducing the complication incidence rate and fatality rate.

The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma.

Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (-87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets ( PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis.

Premalignant alteration assessment in liver-like tissue derived from embryonic stem cells by aristolochic acid I exposure.

The in vitro predictive evaluation of chemical carcinogenicity based on hepatic premalignance has so far not been established. Here, we report a novel approach to investigate the premalignant events triggered by human carcinogen aristolochic acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6 phenotypic characteristics. Hepatocytes expressed STAT3/p-STAT3, c-Myc and Lin28B in parallel. Some of them displayed the dedifferentiation characteristics, such as full of α-fetoprotein granules, increase in size, and nucleocytoplasmic shuttle of Oct4. When these cells were injected into mice, the xenografts mostly displayed the uniform area of hepatic-like tissue with malignant nuclei. The hepatic malignant markers, α-fetoprotein, cytokeratin 7 and cytokeratin 19, were co-expressed in albumin-positive areas, respectively. In conclusion, we established an approach to predict the hepatic premalignance triggered by carcinogen AAI. This premalignant assay system might aid to evaluate the effects of potential carcinogens in liver, and probably to screen the protecting against hepatocarcinogenic efficacy of pharmaceuticals in vitro.

[BCL-2/IgH translocation in peripheral blood cells of healthy Chinese individuals of Han nationality located in Zhejiang area].

OBJECTIVE: To investigate the relationship between the frequency of BCL-2/IgH rearrangement in peripheral blood cells of healthy Chinese individuals of Han nationality located in Zhejiang area and the low incidence of follicular lymphoma (FL). METHODS: Nested-PCR and direct DNA sequencing were used to detect the Bcl-2/IgH rearrangement in peripheral blood cells of 196 healthy individuals. DNA sequences involved were then searched and aligned in NCBI database to confine the broken points in major breakpoint region and the IgH segments involved. RESULTS: First, in this sample the frequency of BCL-2/IgH translocation in Chinese individuals of Han nationality located in Zhejiang area is 9.66%, being much lower than that in North America and Europe countries. Second, the breakpoints tend to fall into 3 clusters: 3055, 3116 and 3165 bp. Usage of J6 segment is most common. Third, There are different subclones of BCL-2/IgH rearrangements in the same individual. CONCLUSION: The low frequency of BCL-2/IgH translocation in healthy Chinese individuals of Han nationality located in Zhejiang area may be one of the reasons for the difference in the incidence of FL between China and Western countries.

Association of tumor necrosis factor α -308G/A and interleukin-6 -174G/C gene polymorphism with pneumonia-induced sepsis.

PURPOSE: Sepsis is a lethal outcome of the inflammation and coagulation process. Human interleukin (IL)-6 and tumor necrosis factor (TNF) α are well-known inflammation factors closely associated with sepsis. In the present study, we aim to investigate the association of promoter-region polymorphisms IL-6 (-174G/C) rs1800795 and TNF-α (-308G/A) rs1800629 with pneumonia-induced sepsis. MATERIALS AND METHODS: A total of 277 Chinese patients with severe pneumonia-induced sepsis were recruited into this study. All study participants were admitted to the intensive care unit until discharge or death in the First Affiliated Hospital of Zhengzhou University from July 2010 to July 2014. The patients were classified as severely septic, septic shock, and mortality. Clinical data and demographic information were recorded. TaqMan genotyping was performed to detect single nucleotide polymorphism distribution. RESULTS: The genotype results demonstrated that carriers of the TNF-α rs1800629 A allele had a 4.28-fold higher risk for septic shock (adjusted odds ratio [OR], 4.28; 95% confidence interval [CI], 2.24-8.18; P < .01) compared with severe sepsis, and carriers of the IL-6 rs1800795 C allele had a 2.42-fold higher risk for septic shock (OR, 2.42; 95% CI, 1.08-5.45; P < .01) compared with severe sepsis. No significant difference of SNP distribution was found between the survivors and the nonsurvivors. After the results were adjusted for age and the outcomes of blood cultures, a multivariate logistic regression analysis showed similar results. Individuals with the TNF-α 308 rs1800629 A allele (adjusted OR, 2.96; 95% CI, 1.30-7.87) or the IL-6 rs1800795 C allele (adjusted OR, 1.87; 95% CI, 1.03-3.61) had a higher prevalence of septic shock. However, these SNP distribution differences were not associated with mortality. CONCLUSIONS: In intensive care unit patients, the TNF-α -308A allele and the IL-6 rs1800795 allele variants were susceptibility risk factors for septic shock induced by pneumonia.