Clinical analysis of infectious mononucleosis complicated with acute acalculous cholecystitis.

Objective: This study aimed to investigate specific clinical diagnostic methods for children with infectious mononucleosis (IM) complicated by acute acalculous cholecystitis (AAC). Methods: We conducted a retrospective analysis of 171 cases of IM diagnosed in the infectious disease ward of Children's Hospital of Nanjing Medical University between January 2020 and December 2020. All IM patients underwent abdominal ultrasound examinations to assess the liver, gallbladder, and spleen. Fourteen patients with symptoms of AAC underwent a follow-up assessment one week later. Results: The estimated incidence of AAC in hospitalized IM children was 8.2%. Both groups of patients presented with fever, abdominal pain, and eyelid edema upon admission. Characteristic radiological findings of AAC were observed, including gallbladder (GB) distention, increased GB wall thickness and increased common bile duct diameter. Analysis of laboratory results revealed no statistically significant differences in leukocyte, absolute lymphocyte count, CD3+, CD3 + CD4+, CD3+ CD8+, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), or Gamma-Glutamyl Transferase (GGT) levels between the AAC(+) and AAC(-) groups on admission. However, these parameters were not significant risk factors for AAC. After discharge, relevant indicators in non-AAC patients gradually decreased to normal levels, while those in AAC(+) patients did not show a significant decrease. Conclusion: While cases of IM complicated by AAC are relatively uncommon, the utilization of abdominal ultrasound offers a reliable tool for confirming this diagnosis. Routine abdominal ultrasound examinations are recommended for IM patients to improve early detection and treatment of associated conditions.

Computational design and experimental confirmation of conformationally constrained peptides to compete with coactivators for pediatric PPAR[Formula: see text] by minimizing indirect readout effect.

The peroxisome proliferator-activated receptor-[Formula: see text] (PPAR[Formula: see text]) is a member of PPAR nuclear receptor family, and its antagonists have been widely used to treat pediatric metabolic disorders. Traditional type-1 and type-2 PPAR[Formula: see text] antagonists are all small-molecule compounds that have been developed to target the ligand-binding site (LBS) of PPAR[Formula: see text], which is not overlapped with the coactivator-interacting site (CIS) of PPAR[Formula: see text]. In this study, we described the rational design of type-3 peptidic antagonists that can directly disrupt PPAR[Formula: see text]-coactivator interaction by physically competing with coactivator proteins for the CIS site. In the procedure, seven reported PPAR[Formula: see text] coactivator proteins were collected and eight 11-mer helical peptide segments that contain the core PPAR[Formula: see text]-binding LXXLL motif were identified in these coactivators, which, however, possessed a large flexibility and intrinsic disorder when splitting from coactivator protein context, and thus would incur a considerable entropy penalty (i.e. indirect readout) upon binding to PPAR[Formula: see text] CIS site. By carefully examining the natively folded conformation of these helical peptides in their parent protein context and in their interaction mode with the CIS site, we rationally designed a hydrocarbon bridge across the solvent-exposed, ([Formula: see text], [Formula: see text]+ 4) residues to constrain their helical conformation, thus largely minimizing the unfavorable indirect readout effect but having only a moderate influence on favorable enthalpy contribution (i.e. direct readout) upon PPAR[Formula: see text]-peptide binding. The computational findings were further substantiated by fluorescence competition assays.

Risk factors for respiratory assistance in premature infants.

Premature infants are prone to dyspnea after birth due to immature development, and some infants require respiratory assistance. However, the risk factors for respiratory assistance in premature infants are rarely reported. The present study enrolled 3,394 premature infants (665 infants had been provided with respiratory assistance and 2,729 had not used respiratory assistance) to retrospectively analyze the risk factors associated with respiratory aid. The multivariate logistic regression analysis demonstrated that placental abnormality [odds ratio (OR)=1.284; P=0.048], the male sex (OR=0.696; P=0.001), delivery via cesarean section (OR=1.538; P<0.001), low 1-min Apgar score (OR=0.727; P<0.001), low birth weight (OR=0.999; P=0.005) and low gestational age (OR=0.616; P<0.001) were independent risk factors for respiratory assistance in premature infants. Overall, a number of risk factors, including placental abnormality, cesarean section, low 1-min Apgar score, low birth weight and small gestational age, were identified for respiratory assistance in premature infants. By conducting a risk assessment of risk factors at birth and using this information to provide timely respiratory assistance, the survival rates of premature infants may increase.

Exosome-Mediated MiR-155 Transfer Contributes to Hepatocellular Carcinoma Cell Proliferation by Targeting PTEN.

BACKGROUND Most eukaryocytes release nano vesicles (30-120 nm), named exosomes, to various biological fluids such as blood, lymph, and milk. Hepatocellular carcinoma (HCC) is one of the tumors with the highest incidence rate in primary malignant carcinoma of the liver. However, the mechanism of HCC proliferation remains elusive. In this study, we aim to explore whether HCC cell-derived exosomes affect the proliferation of cancer cells. MATERIAL AND METHODS Exosomes were isolated from HCC cells by ultracentrifugation and were visualized the phenotype by transmission electron microscopy. Cell proliferation was detected by Cell Counting Kit-8 assays and EdU (5-ethynyl-2-deoxyuridine) incorporation assays. Dual-luciferase assays were performed to validate the paired correlation of miR-155 and 3'-UTR of PTEN (gene of phosphate and tension homology deleted on chromosome 10). A xenograft mice model was constructed to verify the effect of exosome-mediated miR-155 on cell proliferation in vivo. RESULTS Our finding showed that miR-155 was enriched in exosomes released from HCC cells. The exosome-containing miR-155 transferred into new HCC targeted cells and lead to the elevation of HCC cells' proliferation. Besides, the exosomal miR-155 directly bound to 3'-UTR of PTEN leading to the reduction of relevant targets in recipient liver cells. The knockdown of PTEN attenuated the proliferation of HCC cells treated with the exosomal miR-155. Moreover, nude-mouse experiment results revealed a promotional effect of the exosomal miR-155 on HCC cell-acquired xenografts. CONCLUSIONS Our study indicated that exosomal-specific miR-155 transfers to adjacent and/or more distant cells and stimulates the proliferation of HCC cells.

Polymorphisms of p53 and MDM2 genes are associated with severe toxicities in patients with non-small cell lung cancer.

Adverse events in platinum-based chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) are major challenges. In this study, we investigated the role of the p53 and MDM2 genes in predicting adverse events in NSCLC patients treated with platinum-based chemotherapy. Specifically, we examined the p53 p. Pro72Arg (rs1042522), MDM2 c.14 + 309T>G (rs2279744) and MDM2 c.- 461C > G (rs937282) polymorphisms using PCR-based restriction fragment length polymorphism (RFLP) in 444 NSCLC patients. We determine that MDM2 c.14 + 309T > G was significantly associated with severe hematologic and overall toxicities for advanced NSCLC patients treated with platinum-based chemotherapy, especially for patients aged 57 and younger. This was also true for patients with adenocarcinoma. Second, we determine that severe gastrointestinal toxicities in patients with heterozygous MDM2 c.-461C > G were significantly higher than in patients with the G/G genotype. Third, patients with the MDM2 c.-461C > G - c.14 + 309T > G CT haplotype show much higher toxicities than those of CG haplotype. Moreover, patients carrying the MDM2 c.-461 > G -c.14 + 309T > G CG/CT diplotype exhibited higher toxicities than those carrying CG/CG. Fourth, we found that the p53 p. Pro72Arg polymorphism interacts with both age and genotype. In addition, no significant associations were observed between the 3 SNPs and the response to first-line platinum-based chemotherapy in advanced NSCLC patients. In summary, we found that the p53 p. Pro72Arg, MDM2 c.14 + 309T > G and MDM2 c.-461C > G polymorphisms are associated with toxicity risks following platinum-based chemotherapy treatment in advanced NSCLC patients. We suggest that MDM2 c.14 + 309T > G may be used as a candidate biomarker to predict adverse events in advanced NSCLC patients who had platinum-based chemotherapy treatment.

Downregulation of galectin-3 causes a decrease in uPAR levels and inhibits the proliferation, migration and invasion of hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. Galectin-3 (Gal-3), a multifunctional ß-galactoside-binding protein, is highly expressed and associated with the prognosis of HCC. However, the functions of Gal-3 in HCC cells are not fully understood. To address the function of Gal-3 in HCC cells, we used small interfering RNA (siRNA) to knock down Gal-3 expression in HepG2, an HCC cell line. We found that in vitro the silencing of Gal-3 decreased the proliferative activity, colony formation ability, migratory and invasive potential of HepG2 cells. The silencing of Gal-3 significantly decreased the mRNA and protein levels of urokinase-type plasminogen activator receptor (uPAR) as well as uPAR's downstream signaling transduction pathway, including phosphorylation of AKT. Furthermore, the downregulation of Gal-3 by siRNA resulted in significantly decreased activity of the MEK/ERK signaling pathway, and the treatment of HepG2 cells with MEK/ERK inhibitor U0126 significantly reduced the mRNA and protein levels of uPAR. Taken together, our results suggest that Gal-3 modulates uPAR expression via the MEK/ERK pathway, and that Gal-3 may be a potential therapeutic target for the treatment of HCC.