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.

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

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

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.

OBJECTIVETo investigate the expression of miR-9 in B lymphocytes, B cell lymphoma and classical Hodgkin's lymphoma (cHL) cell lines and its significance.

METHODSCD19(+) B lymphocytes were sorted from normal lymph node by magnetic beads. Total cellular micro-RNA was extracted from cHL cell line L428, B cell lymphoma cell lines Ly1 and Ly10 (diffuse large B cell lymphoma), Raji cells (Burkitt's lymphoma) and CD19(+) B lymphocytes, respectively. These micro-RNAs were separately transformed into cDNA by reverse transcription. The expression levels of miR-9 were measured by fluorescence quantitative PCR. In situ hybridization was used to detect the expression of miR-9 in cell lines.

RESULTSThe expression of miR-9 was high in L428 cells (104.44 ± 1.61), and low in cell lines of B cell lymphoma (Ly1: 2.17 ± 0.38; Ly10: 1 ± 0.015; Raji: 2.65 ± 0.89), and extremely low in CD19(+) B lymphocytes (0.0026 ± 0.00040). Compared with that in the other cell lines, the expression of miR-9 in L428 cells was statistically significant (P < 0.05). miR-9 localized in the cytoplasm diffusely and strongly in L428, but scattered and slightly with some prominent distribution around the nuclear membranes in Ly1 and Ly10, and only weakly in Raji.

CONCLUSIONSmiR-9 highly expressed in cHL cell line and might be a molecular marker for diagnosis and treatment of cHL.

B-Lymphocytes ; metabolism ; Cell Line, Tumor ; Cell Lineage ; Hodgkin Disease ; metabolism ; pathology ; Humans ; Lymphoma, B-Cell ; metabolism ; pathology ; MicroRNAs ; metabolism

OBJECTIVETo investigate the clinical features, differential diagnosis and management of congenital stenosis of external auditory canal (CSEAC) with cholesteatoma.

METHODSThe clinical information for 10 cases of CSEAC with cholesteatoma was retrospectively reviewed.

RESULTSThe patients' ages ranged from 4.75 to 22 years (average 12 years). The diameter of the external auditory canal (EAC) was < 2 mm. All 10 ears had a history of postural fistulae or sinuses. Bone erosion of EAC was distinctly shown in high-resolution computed tomography (HRCT) of all cases, as well as soft tissue masses, which led to enlargement of the bony canals. All patients underwent canaloplasty; eight ears received hearing reconstructions at the same time. Cholesteatoma in EACs was confirmed during the operations, accompanied by compression and destruction of the post-superior and/or inferior bony wall. Postoperative pathologic examinations proved the diagnosis of cholesteatoma, and excluded any tissue of bronchial cleft cyst or fistula. After a follow-up 1 to 3 years, no recurrent cholesteatoma was found in any of the 10 cases. All reconstructed EACs were clean and smooth. The hearing levels in the eight ears that received hearing reconstructions improved 20 - 35 dBHL.

CONCLUSIONSIn CSEAC with cholesteatoma, the bony wall of EAC is most commonly involved. This involvement will lead to bone erosion of the EAC and may subsequently lead to the formation of postural or cervical sinuses. HRCT of temporal bone can show characteristic signs of soft tissue mass in EAC, with adjacent bone erosion.

Adolescent ; Child ; Child, Preschool ; Cholesteatoma ; complications ; diagnosis ; surgery ; Constriction, Pathologic ; congenital ; Cutaneous Fistula ; complications ; diagnosis ; surgery ; Ear Canal ; abnormalities ; Ear Diseases ; congenital ; diagnosis ; surgery ; Female ; Humans ; Male ; Retrospective Studies ; Young Adult

Aged ; Antineoplastic Agents ; administration & dosage ; Cystectomy ; Humans ; Infusions, Intra-Arterial ; Male ; Neoplasm Recurrence, Local ; Pelvic Neoplasms ; drug therapy ; Urinary Bladder Neoplasms ; surgery

BACKGROUNDBladder recurrent disease is still a challenge in the treatment of upper tract urothelial carcinoma (UTUC). This controlled study aims to investigate the efficacy of early clipping of the distal ureter prior to nephroureterectomy (NU) to prevent bladder recurrence after UTUC.

METHODSPatients with clinical diagnosis of UTUC were subjected to open trans-peritoneal NU and were randomly divided into two groups. One group received modified NU: clipping the distal ureter prior to NU; while the other group underwent traditional standard NU. Subsequent bladder recurrence was the primary endpoint.

RESULTSFrom January 2007 to December 2009, 85 eligible cases were enrolled in this study. Modified NU and standard NU were performed on 42 and 43 patients, respectively. Operation time ((215.73 ± 21.26) minutes vs. (220.19 ± 15.35) minutes), blood loss ((105.15 ± 11.32) ml vs. (110.12 ± 9.07) ml), transfusion event (11.20% vs. 9.78%), and the in-patient time (10.0 days vs 9.5 days) were not significant between the two groups. After a median follow-up of 28 months (5 - 60), six (14.3%) cases who received modified NU had bladder recurrence, which was significantly lower compared with 15 (34.9%) patients from the group that underwent standard NU (P = 0.026). In univariate and multivariate analysis, tumor grade (HR 4.33, 95%CI 2.66 - 6.30, P = 0.01) and operation type (HR 2.35, 95%CI 1.53 - 3.48, P = 0.041) were independent risk factors for subsequent bladder recurrence after UTUC.

CONCLUSIONSClipping the distal ureter at the beginning of NU significantly reduces bladder recurrence after UTUC. It is reasonable to conclude that clipping the distal portion of ureter trans-peritoneal is an effective surgical procedure for the treatment of UTUC.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Nephrectomy ; methods ; Ureter ; surgery ; Urinary Bladder Neoplasms ; surgery