Animals ; Cell Differentiation ; genetics ; physiology ; Humans ; MicroRNAs ; genetics ; Ossification, Heterotopic ; genetics ; Signal Transduction ; genetics ; physiology

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.

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.

Female ; Humans ; Lymphoma, T-Cell ; diagnosis ; Middle Aged ; Multiple Myeloma ; diagnosis

OBJECTIVETo understand the HBV infection rate of peripheral blood mononuclear cells (PBMCs) from fetuses of HBsAg positive mothers, associated risk factors and to explore the clinical significance of detecting HBV infected PBMCs.

METHODSSixty eight pregnant women who were delivered at the First Hospital of Xi'an Jiaotong University, China from August 1995 to February 1997, and their newborns were studied. They were divided into two groups according to their status of HBV serological markers. The study group included 50 cases who were serum HBsAg positive and 18 cases without any HBV serum markers served as control group. All these cases had no symptoms of hepatitis, high risk premature labor, premature delivery and hypertensive disorder complicating pregnancy. Age and gestational age were matched in two groups. Blood samples (5 mL) were taken from the peripheral vein of pregnant women before delivery and from newborns within 24 h after birth, before inoculation of HBV vaccine (HBVac) and injection of hepatitis B immunoglobulin (HBIG). PBMCs were isolated. The sera and PBMCs were stored at -80 degrees C. HBV-DNA in serum and PBMCs were detected with nested polymerase chain reaction (n-PCR). Two pairs of oligonucleotide primers, the outer primer pair for first PCR and inner primer pair for second PCR, designed according to region S of HBV genome were synthesized by Shanghai Cell Biology Institute of Chinese Academy of Science.

RESULTSThe detection rate of HBV-DNA in serum and PBMCs from HBsAg positive pregnant women was 60.0% (30/50) and 40.0% (20/50), respectively. The detection rate of HBV-DNA in serum and PBMCs from newborns of HBsAg positive pregnant women was 46.0% (23/50) and 30.0% (15/50), respectively. Ten newborns were HBV-DNA positive in serum only, 2 were positive in PBMCs only and 13 were positive in both serum and PBMCs. In the control group, HBV-DNA was not detected in PBMC nor in serum. The positive rate of HBV-DNA in PBMCs of newborns was significantly higher in the group of mothers who were HBV-DNA or HBeAg positive in serum (P < 0.05, P < 0.01); the positive rate was significantly higher in the group of mothers who were HBV-DNA positive in both serum and PBMC than that in the group of mothers who were serum HBV-DNA positive only (P < 0.01); and it was markedly higher in the group of mothers who were PBMC HBV-DNA positive than that in group of mothers who were HBV-DNA negative in PBMCs (P < 0.01). The positive rate of HBV-DNA in PBMCs of newborns was significantly higher in the group of newborns who were HBV-DNA positive in serum than that in the group of newborns who were HBV-DNA negative in serum (P < 0.05).

CONCLUSIONSThe positive rate of HBV-DNA in PBMCs from newborns of HBsAg positive pregnant women was 30.0% (15/30). It was related to HBV viremia level and HBV-DNA status in PBMCs of mothers and newborns. Detection of HBV-DNA in PBMCs may be an important supplementary method to determine intrauterine HBV infection, and can predict the response to HBV vaccine.

Adult ; Case-Control Studies ; DNA, Viral ; blood ; Female ; Hepatitis B Vaccines ; administration & dosage ; Hepatitis B virus ; immunology ; isolation & purification ; Humans ; Immunoglobulins ; administration & dosage ; Infant, Newborn ; blood ; Infectious Disease Transmission, Vertical ; prevention & control ; Injections, Intramuscular ; Leukocytes, Mononuclear ; virology ; Male ; Mothers ; Polymerase Chain Reaction ; Pregnancy ; blood ; Risk Factors ; Time Factors ; Treatment Outcome

Objective： This study was designed to explore the relationship between clinicobiological acting and expression of p21 protein and estrogen receptor(ER) in colorectal cancer. Methods： The intensity of expression of p21 protein and ER for 206 patients with colorectal cancers were determined by labeled-streptokinase avidin-biotin(LSAB) assay. Results： The expression of p21 protein is negatively correlated with that of ER in colorectal cancer(r=-0.6613, P<0.01). The intensity of expression of p21 protein and ER in colorectal cancers were not related with the patients age, sexuality, tumor position, pathological type, histological type, Dukes stage etc.(r< 0.4,P>0.05). Both the expressions were related to the prognosis of colorectal cancer(P<0.01). Higher the intensity of expression of p21 protein worse the patients prognosis, and higher the intensity of expression of ER better the patient s prognosis. Conclusions： The abnormal expression of p21 protein is related to the dysbolism of estrogen in colorectal cancer. The detection of p21 protein and ER are helpful for diagnosis and prognostic evaluation for colorectal cancer.

Objective To investigate the effect of fluid shear stress (FSS) on the expression of B lymphoma MoMLV insertion region 1 (Bmi-1) in bone mesenchymal stem cells (BMSCs) and possible signal transduction mechanism.Methods BMSCs were isolated from SD rats and FSS at different magnitude (0.5,1.5,3.0 Pa)and under different time phase (1,2,6,24 h) were loaded by parallel-plate flow chamber system.The expression of Bmi-1 was measured by real-time RT-PCR at mRNA level and the levels of phosphorylated Akt (p-Akt)and extracellular signalregulated kinase 1/2 (p-ERK1/2) were detected by Western blotting.The signaling inhibitors,wortmannin (PI3K specific inhabitor) and PD98059 (ERK1/2 specific inhabitor),were used to investigate possible mechanical signal transduction pathway.Results Bmi-1mRNA expression increased when BMSCs were exposed to 1.5 Pa FSS for 1 h and reached the peak at 24 h.All FSS with different magnitude could increase Bmi-1 expression,especial at high FSS (3.0 Pa).Meanwhile,FSS resulted in a significant activation of p-Akt and p-ERK1/2 in BMSCs.After treated with wortmannin,the expression of Bmi-1 was inhibited prominently,however,PD98059,the expression of Bmi-1 did not change.Conclusions FSS can activate the expression of Bmi-1,the amount of Bmi-1 expression was closely related to the stimulating time and the magnitude of FSS,and Akt signal molecule plays an important role during the process.These findings provide significant references for studying the mechanical biological mechanisms of stem cell differentiation.

OBJECTIVESTo investigate the oncologic outcomes of surveillance, retroperitoneal lymph node dissection (RPLND) and primary chemotherapy in patients with clinical stage Ia nonseminomatous germ cell testicular tumors (CS Ia NSGCT) and to analyze risk factors for relapse.

METHODSPatients with CS Ia NSGCT were retrospectively reviewed. Totally 72 patients were enrolled and grouped according to three different treatment after orchiectomy, among them 33 cases in surveillance group, 24 cases in RPLND group and 15 cases in primary chemotherapy group. Disease progressive free survival and disease specific survival were compared using Kaplan-Meier analysis. Cox regression analysis was used to confirm variables those were associated with disease progression.

RESULTSAll 72 patients were followed-up at mean 62 months (12 - 175 months), 6 patients had evidence of relapse. Both the 5-year disease specific survival and 5-year overall survival rate were 100%. For surveillance, chemotherapy and RPLND, cumulative 5-year PFS rates were 84.0%, 93.3% and 100%, respectively. Relapse rate was higher in surveillance group than in RPLND group (17.8% vs. 0, χ² = 3.99, P = 0.04). Patients with the history of cryptorchidism also have higher relapse rate than without (37.5% vs. 4.7%, χ² = 10.02, P = 0.01). In the surveillance cohort, relapse rates were significantly higher in patients with a predominant component of embryonal carcinoma (3/6 vs. 7.4%, χ² = 6.93, P = 0.04) and for those over 13 years of age (23.1% vs. 5.3%, χ² = 4.33, P = 0.04). On multivariate analysis, treatment mode of patients (OR = 0.08, 95% CI: 0.06-0.36, P = 0.03) and patients with a history of cryptorchidism (OR = 25.3, 95% CI: 6.57-78.42, P = 0.04) were independent predictors of relapse.

CONCLUSIONSSurveillance, RPLND and adjuvant chemotherapy could be reliable strategies in compliant stage Ia nonseminoma patients and achieve satisfactory overall survival. Relapse rate is relatively higher for patients with surveillance. Those who are older or have a history of cryptorchidism experience a higher risk of relapse.

Adolescent ; Adult ; Aged ; Chemotherapy, Adjuvant ; Child ; Child, Preschool ; Humans ; Infant ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms, Germ Cell and Embryonal ; therapy ; Orchiectomy ; Postoperative Period ; Retrospective Studies ; Risk Factors ; Survival Rate ; Testicular Neoplasms ; therapy ; Treatment Outcome ; Young Adult

OBJECTIVETo study changes of plasma motilin concentration and it's effect on enteral nutrition in premature infants.

METHODSThe plasma motilin concentration of 72 premature infants was measured within 12 hours after birth before enteral feeding and on day 3 and 7 of life by using radioimmunoassay. Sixteen full-term neonates were enrolled as controls.

RESULTS(1) The plasma concentrations of motilin in premature infants before enteral feeding after birth and on day 3 and 7 were 198.65 +/- 58.42 ng/L, 248.83 +/- 56.00 ng/L, and 376.77 +/- 139.46 ng/L, respectively, which were significantly lower than those in the control group (300.33 +/- 67.15 ng/L, 334.26 +/- 83.81 ng/L, 510.64 +/- 179.85 ng/L) (P < 0.001 or < 0.01). There was positive correlation between the concentration and gestational age, age in day and the volume of milk. On day 7 the level of motilin was higher than the pre-enteral feeding level of the full term control group. (2) The plasma motilin concentration in feeding un-tolerated premature infants group was lower than that in the normal group, especially on day 3 of life (P < 0.05). (3) Early enteral feeding could improve the plasma motilin levels, gastrointestinal motility and nutrition tolerance in premature infants.

CONCLUSIONSThe gastrointestinal functions of premature infants are adaptable to enteral nutrition. Early enteral feeding (including minimal enteral nutrition and non-nutritive sucking) can promote adaptive rapid growth and development of intestine.

Enteral Nutrition ; Female ; Humans ; Infant, Low Birth Weight ; blood ; Infant, Newborn ; Infant, Premature ; blood ; Infant, Very Low Birth Weight ; blood ; Male ; Motilin ; blood ; Time Factors

OBJECTIVETo study the expression pattern of cd99l2 gene during zebrafish development, the RNA probes for whole-mount in situ hybridization were prepared in this study.

METHODSThe cd99l2 fragment obtained by RT-PCR was cloned into pGM-T Easy, then the plasmids were linearized with the restriction enzymes SacII or SalI. Using Sp6 or T(7) RNA polymerase, the digoxingenin-labeled antisense and sense probes were synthesized and confirmed by whole-mount in situ hybridization.

RESULTSThe plasmid cd99l2/pGM-T was constructed. cd99l2 gene expression pattern during embryogenesis of zebrafish was examined using the antisense probe, and intense expression was detected in the central nervous system during zebrafish development.

CONCLUSIONThe antisense probe can be used for study of the spatial and temporal distribution of cd99l2 during zebrafish development using the sense probe as control.

Animals ; Central Nervous System ; embryology ; Cloning, Molecular ; Digoxigenin ; chemistry ; Gene Expression Regulation, Developmental ; Oligonucleotide Probes ; RNA Probes ; Uridine Triphosphate ; chemistry ; Zebrafish ; embryology ; genetics ; Zebrafish Proteins ; genetics