Escherichia coli LTB26 mutant enhances immune responses to rotavirus antigen VP8 in a mouse model.

Adjuvant is a major supplementary component of vaccines to boost adaptive immune responses. To select an efficient adjuvant from the heat-labile toxin B subunit (LTB) of E. coli, four LTB mutants (numbered LTB26, LTB34, LTB57, and LTB85) were generated by multi-amino acid random replacement. Mice have been intranasally vaccinated with human rotavirus VP8 admixed. Among the four mutants, enzyme-linked immunosorbent assay (ELISA) revealed that LTB26 had enhanced mucosal immune adjuvanticity compared to LTB, showing significantly enhanced immune responses in both serum IgG and mucosal sIgA levels. The 3D modeling analysis suggested that the enhanced immune adjuvanticity of LTB26 might be due to the change of the first LTB α-helix to a ß-sheet. The molecular mechanism was studied using transcriptomic and flow cytometric (FCM) analysis. The transcriptomic data demonstrated that LTB26 enhanced immune response by enhancing B cell receptor (BCR) and major histocompatibility complex (MHC) II+-related pathways. Furthermore, LTB26 promoted Th1 and Th2-type immune responses which were confirmed by detecting IFN-γ and IL-4 expression levels. Immunohistochemical analysis demonstrated that LTB26 enhanced both Th1 and Th2 type immunity. Therefore, LTB26 was a potent mucosal immune adjuvant meeting the requirement for use in human clinics in the future.

Prevalence and Influencing Factors of Physical Restraints in Intensive Care Units: A Retrospective Cohort Study.

Purpose: Physical restraints are used routinely in intensive care units (ICUs) and have negative effects. It is critical to identify the impact factors of physical restraints on critically ill patients. The present study investigated the prevalence of physical restraints and impact factors associated with their use in a large cohort of critically ill patients over one year. Patients and Methods: A retrospective cohort study was performed in multiple ICUs at a tertiary hospital in China in 2019 using observational data from electronic medical records. The data consisted of demographics and clinical variables. Logistic regression was used to assess the independent impact factors for the use of physical restraint. Results: The analysis consisted of 3776 critically ill patients with a prevalence of physical restraint use of 48.8%. The logistic regression analysis indicated that physical restraint use was associated with independent risk factors, including surgical ICU admission, pain, tracheal tube placement, and abdominal drainage tube placement. Physical restraint use was associated with independent protective factors, including male sex, light sedation, muscle strength, and ICU length of stay. Conclusion: The prevalence of physical restraint use in critically ill patients was high. Tracheal tubes, surgical ICU, pain, abdominal drainage tubes, light sedation, and muscle strength were independent variables associated with the use of physical restraint. These results will assist health professionals in identifying high-risk physical restraint patients based on their impact factors. Early removal of the tracheal tube and abdominal drainage tube, pain relief, light sedation, and improvements in muscle strength may help reduce the use of physical restraints.

Multifaceted regulation and functions of replication factor C family in human cancers.

Replication factor C (RFC) family is a complex comprised of the RFC1, RFC2, RFC3, RFC4, and RFC5 subunits, which acts as a primer recognition factor for DNA polymerase. It is reported that RFC, biologically active in various malignant tumors, may play an important role in the proliferation, progression, invasion, and metastasis of cancer cells. It could act as an oncogene or tumor suppressor gene based on the cellular and histological characteristics of the tumor. In this review, we summarized the updated researches on the structure, physiological function, and expression pattern of RFC in a variety of tumors, the underlying mechanisms on carcinogenesis, and the potentials of RFC family members in the diagnosis and prognosis prediction.

RNA activation technique and its applications in cancer research.

RNA activation (RNAa) is a mechanism of gene activation mediated by small activating RNAs. The activation of gene expression by small activating RNA has excellent targeting specificity and flexibility, with a persistent and strong effect. Studies have shown that the RNAa technique has broad prospects for application in the research on tumor pathogenesis and the treatment of tumors. This paper reviews the literature on RNAa with regard to the course of discovery, the mechanisms and characteristics of action, and the current status and prospects of application.

Comparison of sentinel lymph node detection performances using blue dye in conjunction with indocyanine green or radioisotope in breast cancer patients: a prospective single-center randomized study.

OBJECTIVE: This randomized study aimed to compare the clinical efficacy between the novel dual tracer composed of indocyanine green (ICG) and blue dye (BD) and the conventional dual tracer composed of radioisotope and BD for sentinel lymph node (SLN) mapping in patients with breast cancer. METHODS: This study enrolled 471 clinically lymph node-negative patients with primary breast cancer. All patients underwent mastectomy, and those undergoing sentinel lymph node biopsy (SLNB) were randomized to receive blue dye plus radioisotope (RB group) or BD plus ICG (IB group). The detection performances on SLN identification rate, positive SLN counts, detection sensitivity, and false-negative rate were compared between the two groups. RESULTS: In the IB group, 97% (194/200) of the patients who underwent the ICG and BD dual tracer injection showed fluorescent-positive lymphatic vessels within 2-5 min. The identification rate of SLNs was comparable between the IB group (99.0%, 198/200) and the RB group (99.6%, 270/271) (P = 0.79). No significant differences were observed in the identification rate of metastatic SLNs (22.5% vs. 22.9%, P > 0.05, RB group vs. IB group, the same below), positive SLN counts (3.72 ± 2.28 vs. 3.91 ± 2.13, P > 0.05), positive metastatic SLN counts (0.38 ± 0.84 vs. 0.34 ± 0.78, P > 0.05), SLNB detection sensitivity (94.4% vs. 92.5%, P > 0.05), or false-negative rate (5.6% vs. 7.5%, P > 0.05) between the two groups. CONCLUSIONS: ICG can be used as a promising alternative tracer for radioisotope in SLN mapping, and when it is combined with BD in lymphangiography, it offers comparable detection sensitivity compared to the conventional lymphatic mapping strategies that are widely used in clinical practice.