Abstract: Objective　To investigate the distribution and drug resistance characteristics of pathogenic bacteria in patients with neutropenic acute leukemia (AL) and bloodstream infections (BSI). Methods　The clinical data of 258 neutropenic acute leukemia patients with bloodstream infections, who admitted to Shengjing Hospital of China Medical University from January 2016 to December 2021, were collected and analyzed for pathogenic bacteria and drug resistance. Results A total of 268 strains of pathogenic bacteria were isolated from 258 patients, including 180 strains of gram-negative bacteria (67.16%), 61 strains of gram-positive bacteria (22.76%), and 27 strains of fungi (10.07%). Gram-negative bacteria were mainly Klebsiella pneumoniae (53/268, 19.78%), Escherichia coli (49/268, 18.28%) and Pseudomonas aeruginosa (41/268, 15.30%). Gram-positive bacteria were mainly coagulase negative Staphylococcus (31/268, 11.57%) and Staphylococcus aureus(17/268, 6.34%). The main fungi were Candida tropicalis (25/268, 9.33%). Escherichia coli (33/268, 12.31%) was the most common pathogen isolated from acute myeloid leukemia (AML), followed by Pseudomonas aeruginosa (25/268, 9.33%), coagulase-negative Staphylococcus (18/268, 6.72%) and Candida tropicalis (18/268, 6.72%). Klebsiella pneumoniae (35/268, 13.06%) was the most common pathogen isolated from acute lymphoblastic leukemia (ALL),followed by Pseudomonas aeruginosa (15/268, 5.60%) and Escherichia coli (14/268, 5.22%). The resistance of Gram-negative bacteria to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, meropenem, ertapenem, amikacin, cefoxitin, amoxicillin/clavulanic acid was low. Gram-positive bacteria were sensitive to linezolid and vancomycin. Candida was sensitive to flucytosine, amphotericin B and itraconazole. Conclusions　In patients with granulosa after AL chemotherapy combined with BSI, the pathogenic bacteria isolated from AML are diverse, and the pathogenic bacteria isolated from ALL are mainly gram-negative bacteria. Pathogenic bacteria have different degrees of drug resistance to commonly used antibacterial drugs, so it is important to strengthen the monitoring of the distribution of pathogenic bacteria and the change of drug resistance and rational use of antibacterial drugs to minimize the death of patients.

Objective To detect the expression of TIM-3 (T cell immunoglobulin domain, mucin domain) and its relationship with Treg (regulatory T) cells isolated from peripheral blood mononuclear cells (PBMCs) in the patients with allergic rhinitis (AR), and investigate the role of TIM-3 in the occurrence and development of the allergic rhinitis inflammation. Methods AR patients (AR group, n=30) and healthy subjects (HC group, n=25) were selected as experimental group and control group respectively, and 2 ml peripheral venous bloods were collected from these two groups. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood by density gradient centrifugation. The proportion of CD4+CD25+FoxP3+, reflecting expression of Treg, and TIM-3+Treg was detected by flow cytometry. The relationship between TIM-3 expression and Treg cells was analyzed. The expression of TIM-3 on the surface of CD4+CD25+FoxP3+ Treg cells was analyzed by flow cytometry. Then the TIM-3 expression was blocked, and its influence on Treg cells was observed. Results The percentage of Treg cells in peripheral blood of patients with AR (1.16%±0.13%) was lower than that of healthy controls (5.12%±0.11%) (Z=–6.339, P<0.01). The expression of TIM-3 on the surface of Treg cells in AR patients (11.76%±1.07%) was higher than that in healthy controls (3.15%±0.22%) (Z=–5.570, P<0.01). The expression of CD4+CD25+FoxP3+Treg cells in AR patients was negatively correlated with the expression of TIM-3 on the surface (r=–0.763, P<0.05); The percentage of Treg cells in peripheral blood of AR patients after the block (1.67%±0.76%) was significantly higher than that before block (1.44%±0.78%) (Z=–1.45, P=0.135). The percentage of IL-10 secreted by Treg cells in peripheral blood after block (2.33%±1.45%) was higher than that before block (1.57%±1.12%) (Z=–2.97, P=0.003) in AR patients. Conclusion The expression of TIM-3 in PBMCs may increase in patients with AR, TIM-3 may play an important role in the pathogenesis of AR, and may be related to the imbalance of Treg cells.

The COVID-19 outbreak has drawn attention to viral infectious diseases once again, and the development of antiviral drugs for both known and potentially emerging viruses is of great significance. In recent years, peptides and protein drugs are becoming a hot spot in the field of antiviral drug research and development. Phage display technology, as a powerful tool for screening peptides and protein drugs, has been increasingly concerned in the academic and industrial fields. The present review introduced the basic principle of phage display technology, summarized phage display libraries often used in antiviral drug discovery and their applications, discussed the challenges and future direction of antiviral drug research and development based on phage display technology.

Human violent behavior is a complex behavior which is influenced by genetic and environmental factors. There is a trend in investigating the mechanism of violent behavior by using the genetic methods. This article reviews several candidate genes and advances in epigenetics which are associated with violent behavior. The prospects and significance of violent behavior research from the view of gene polymorphism and epigenetics are also discussed.
Aggression ; Epigenesis, Genetic ; Forensic Genetics ; Humans ; Polymorphism, Genetic ; Violence

The Arabidopsis thaliana tonoplast Na+ /H+ antiporter gene, AtNHX1, was transferred into buckwheat by Agrobacterium-mediated method. Transgenic buckwheat plants were regenerated and selected on MS basal medium supplemented with 2.0mg/L 6-BA, 1.0mg/L KT, 0.lmg/L IAA, 50mg/L kanamycin and 500mg/L carbenicillin. 426 seedlings from 36 resistant calli originated from 864 explants (transformed about at 4.17 percentage) exhibited resistance to kanamycin. The transformants were confirmed by PCR, Southern blotting, RT-PCR and Northern blotting analysis. After stress treatment for 6 weeks with 200mmol/L NaCl, transgenic plants survived, while wild-type plants did not. After 3 days of stress treatment through different concentrations of NaCl, transgenic plants accumulated higher concentration of Na+ and proline than the control plants. However, the K+ concentration of transgenic plants declined in comparison with the control plants. Moreover, the rutin content of the roots, stems and leaves of transgenic buckwheat increased than those of the control plants. These results showed that it could be possible to improve the salt-tolerance of crops with genetic technology.
Adaptation, Physiological ; drug effects ; genetics ; physiology ; Arabidopsis Proteins ; genetics ; physiology ; Blotting, Northern ; Blotting, Southern ; Cation Transport Proteins ; genetics ; physiology ; Fagopyrum ; genetics ; metabolism ; physiology ; Plant Roots ; genetics ; metabolism ; physiology ; Plant Stems ; genetics ; metabolism ; physiology ; Plants, Genetically Modified ; genetics ; metabolism ; physiology ; Potassium ; metabolism ; Proline ; metabolism ; Regeneration ; Reverse Transcriptase Polymerase Chain Reaction ; Rutin ; metabolism ; Sodium ; metabolism ; Sodium Chloride ; pharmacology ; Sodium-Hydrogen Exchangers ; genetics ; physiology ; Transformation, Genetic

OBJECTIVE: To analyze the polymorphism of rs220030, a SNP which is located in the promoter region of small nuclear ribonucleoprotein polypeptide N (SNRPN) gene in the Chinese Han population and to obtain the data of population genetics. METHODS: The denaturing gradient gel electrophoresis (DGGE) method was applied to detect the polymorphism of rs220030 in 100 unrelated and healthy individuals from the Shanghai Han population. The genotyping result of this SNP was confirmed by TaqMan assay in some typical samples. RESULTS: DGGE results showed 4 bands for CT heterozygote, and 1 band for CC or TT homozygote, and those results were confirmed by The TaqMan SNP genotyping assays. Genotyping results showed 34 individuals with CC, 41 with CT and 25 with TT of rs220030. The allele frequencies for C and T were 0.545 and 0.455, respectively. H was 0.500, PIC was 0.373, DP was 0.654, and PE was 0.186. The distribution of genotype frequencies were in Hardy-Weinberg equilibrium. CONCLUSION DGGE is a quick and effective method in the analysis of SNP polymorphism in small population. Statistical parameters of rs220030 for forensic evaluation meet the requirements for forensic identification and paternity testing.
Alleles ; Asian People/genetics* ; China/ethnology* ; DNA Primers ; Denaturing Gradient Gel Electrophoresis/methods* ; Gene Frequency ; Genetic Markers ; Genetics, Population ; Genotype ; Heterozygote ; Humans ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide/genetics* ; Promoter Regions, Genetic ; snRNP Core Proteins/genetics*

Direct DNA delivery procedures (include biolistics method) often resulted in multiple copies of the transgenes in transformants and certain copies of them were rearranged. Integration of multiple copies of the introduced genes was the main reason of gene silencing which meant inhibition or loss of foreign gene expression in filial generations of transformants. In the present work, we compared the influences of maize Ubi-1 promoter and other promoters on copy number of transgenes in maize transgenic plants. Immature embryos from Zea mays L. plants of sib-pollinated of A188 x H99 genotype were used as initial materials. Type- I embryonic calluses derived from preculture of immature embryos were treated on N6 medium containing 0.6 mol/L sucrose for 3 approximately 5 hours and transformed via particle bombardment with PDS1000/He delivery system (Bio-Rad). Bombarded calluses were treated with hyperosmotic N6 medium for 16 approximately 20 hours continuously. Then the cultures were transferred onto normal N6 medium and incubated at 26 degrees C in dark for two weeks and subsequently selected on N6 medium supplemented with 2 or 5 mg/L phosphinothricin (PPT) but without casamino acid for another two weeks. The calluses after selective culture were transferred onto hormone-free MS medium containing 2 or 5 mg/L PPT but without casamino acid, and incubated at 24 degrees C under 16 h illumination for plant regeneration. Regenerated plantlets over 2 cm in height were transferred to Magenta box containing 1/2 hormone-free MS medium. Plantlets over 8 cm in height were transplanted to soil. After growing for one week in greenhouse, the plants were sprayed with 250 mg/L PPT solution. Fertile transgenic maize plants were regenerated and confirmed by Southern blotting and histochemical localization of beta-glucuronidase (GUS) activity. Relations between promoter and copy number of transgenes in transformants were analyzed. Maize transgenic plants possessing an intact copy and another incomplete copy of beta-glucuronidase gene (gus) were obtained in case gus gene under the control of maize Ubi-1 promoter (pUbi:GUS). Simultaneously the co-transformed phosphinothricin acetyltransferase gene (bar) controlled by CaMV 35S promoter in another plasmid (p35S:BAR) also existed with only one copy. When pDB1 and (pUbi:in2) were cobombarded, the regenerated transgenic maize plant exhibited with only one copy of in2 gene too. It suggested that the copy number of transgenes in maize transformants was low if the transgenes controlled by maize Ubi-1 promoter. The possible reason might be that the foreign genes were integrated site-specifically via homologous recombination between Ubi-1 promoter and its endogenous sequences in maize genome, and two cotransformed plasmids had reconstructed as one intact molecule before integrating into maize chromosome. On the contrary, if p35S:BAR was cobom-barded with plasmid pAct:In1 containing rice Act-1 promoter (without maize Ubi-1 promoter), the transgenic maize plants had 4 approximately 8 copies of bar gene. These results reflected that utilization of self gene promoter could reduce the copy number of the transgenes in transgenic plants of certain species itself and avoid the occurrence of gene silencing. T2 seeds have been harvested.
Gene Dosage ; Plant Proteins ; genetics ; Plants, Genetically Modified ; genetics ; Promoter Regions, Genetic ; Ubiquitin C ; genetics ; Zea mays ; genetics

OBJECTIVETo investigate the effect of rhein on the development of hepatic fibrosis.

METHODSThe animal models were made with carbon tetrachloride (CCl(4)) mixed with vegetable oil (3/2, v/v), which was injected subcutaneously twice a week for 6 weeks, and with 5% ethanol for free drinking water. At the same time, Rhein was administrated at the dose of 25 mg/kg or 100 mg/kg once a day for 6 weeks. The changes of both biochemical markers, such as the levels of alanine aminotransferase (ALT), hyaluronic acid (HA), procollagen type III (PCIII) in serum and SOD, malondialdehyde (MDA) in liver, and related histopathological parametres were determined.

RESULTSCompared with the model group, there were three kinds of changes in the larger quantity of rhein treated group. (1) The levels of ALT, HA, PCIII in serum and MDA in liver homogenate were decreased significantly (from 150 U/L +/- 16 U/L to 78 U/L +/- 18 U/L, 321 microg/L +/- 97 microg/L to 217 microg/L +/- 75 microg/L, 31 microg/L +/- 14 microg/L to 16 microg/L +/- 6 microg/L and 3.67 nmol/mg +/- 0.68 nmol/mg to 1.88 nmol/mg +/- 0.34 nmol/mg, respectively, t > or 2.977, P<0.01). However the level of SOD in liver was increased (from 62.45 NU/mg +/- 8.74 NU/mg to 91.26 NU/mg +/- 14.04 NU/mg, t=4.453, P<0.01). (2) The expressions of transforming growth factor beta 1 (TGF-beta 1) and alpha-smooth muscle actin (alpha-SMA) in liver were markedly reduced (P<0.05 and P<0.01). (3) The collagen staining positive area was decreased and the grade of fibrosis was reduced significantly in liver (P<0.05 and P<0.01).

CONCLUSIONRhein can protect hepatocyte from injury and prevent the progress of hepatic fibrosis in rats, which may associate with that rhein plays a role in antioxidation, anti-inflammation, inhibiting the expression of TGF-beta1 and suppressing the activation of hepatic stellate cells (HSCs).

Animals ; Anthraquinones ; pharmacology ; therapeutic use ; Anti-Inflammatory Agents ; pharmacology ; Antioxidants ; pharmacology ; Collagen ; analysis ; Liver ; drug effects ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; antagonists & inhibitors ; Transforming Growth Factor beta1

OBJECTIVETo investigate the effect of baicalein on proliferation and migration of multiple myeloma (MM) cell lines and its molecular mechanism.

METHODSThe MM cell line RPMI-8226 and U266 cells were used as the model, and treated with different concentration and time of baicalein the effect of baicalein on the MM cells proliferation was assessed by MTT assay. With or without baicalein or Interleukin-6 (IL-6) treatment, the β-catenin protein level was analyzed by immunofluorescence assay and western blot assay and mRNA levels of β-catenin, c-myc, cyclin D1 and integrin 7 gene by RT-PCR. Transwell chamber migration assay was used to detect the cells migration ability with different concentration of baicalein cultured.

RESULTSBaicalein inhibited the MM cell line RPMI 8226 and U266 cell proliferation in a dose- and time-dependent manner. It simultaneously inhibited β-catenin protein level to resist the effect of IL-6 on inducing MM cell proliferation, and resulted in decrease of β-catenin, c-myc, cyclinD1 and integrin β7 mRNA levels. Baicalein also decreased migration ability of MM cells in a dose-dependent manner by SDF-1.

CONCLUSIONBaicalein can inhibit MM cells proliferation and migration, and its molecular mechanisms are associated with inhibition of proliferation related genes β-catenin, c-myc, cyclin D1 and integrin β7 expression.

Antigens, CD ; metabolism ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Flavanones ; pharmacology ; Humans ; Integrin alpha Chains ; metabolism ; Interleukin-6 ; pharmacology ; Multiple Myeloma ; metabolism ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; RNA, Messenger ; genetics ; beta Catenin ; metabolism

OBJECTIVETo study the features of histopathologic and ultrastructural pathologic changes of liver biopsy in patients with infantile cholestatic disease, and to investigate its diagnostic significance combining with the clinical data.

METHODSThirty-six children diagnosed as infantile cholestatic disease and received liver biopsy in Chongqing Medical University Children's Hospital from Jun 2007 to Oct 2008 were enrolled and the pathologic and ultrastructural pathologic changes of liver were analyzed.

RESULTSMorphologic changes under light microscope in liver tissues included hepatocyte swelling, hepatocyte denaturation, hepatocyte necrosis, multinucleated giant cell formation, bile duct proliferation, fiber tissues proliferation and inflammatory cells infiltration in liver lobules and portal regions. The characteristics of cholestasis including intralobular cholestasis, acinus formation, feather-like cytoplasmic filaments and bile stasis in bile canaliculi were observed. The morphologic changes of biliary atresia were observed in 7 cases whose image investigations showed no obstruction of biliary tract. Nuclear changes, resolution of cytoplasm, inflammatory cell infiltration, collagen fiber proliferation and increased number of lysosomes were observed under electromicroscope. Two cases of glycogen storage disease, 1 case of Niemann-Pick disease and 1 case of lipid storage disease with unknown cause were confirmed by the combination of histological changes and clinical manifestations.

CONCLUSIONCommon pathologic changes of liver tissues existed under light microscope or electroscope. The diagnosis of hereditary metabolic disorders could be made increasingly by application of these two technologies in clinical practice. It is difficult to diagnose biliary atresia in early childhood by image investigations and the pathological changes of liver tissues are helpful.

Cholestasis ; diagnosis ; etiology ; pathology ; Female ; Humans ; Infant ; Liver ; pathology ; Liver Diseases ; diagnosis ; etiology ; pathology ; Male