Bacterial bioburden of duodenoscope elevator mechanism in different reprocessing stages.

Over the past decade, infections linked to duodenoscopes have become a significant concern, primarily due to the intricate design of the elevator mechanism. Currently, there is limited evidence regarding the bacterial contamination level of the elevator mechanism after clinical use and throughout its various reprocessing stages. This study utilized the swab culture technique to examine the bacterial contamination on the duodenoscope elevator mechanism after clinical use and after 3 reprocessing stages at a Center of tertiary hospital. Our findings revealed severe bacterial contamination after clinical usage, emphasizing that the effectiveness of manual cleaning greatly influences the subsequent high-level disinfection quality.

Exercise intervention for patients with chronic low back pain: a systematic review and network meta-analysis.

Purpose: Chronic low back pain (CLBP) is an aging and public health issue that is a leading cause of disability worldwide and has a significant economic impact on a global scale. Treatments for CLBP are varied, and there is currently no study with high-quality evidence to show which treatment works best. Exercise therapy has the characteristics of minor harm, low cost, and convenient implementation. It has become a mainstream treatment method in clinics for chronic low back pain. However, there is insufficient evidence on which specific exercise regimen is more effective for chronic non-specific low back pain. This network meta-analysis aimed to evaluate the effects of different exercise therapies on chronic low back pain and provide a reference for exercise regimens in CLBP patients. Methods: We searched PubMed, EMBASE, Cochrane Library, and Web of Science from inception to 10 May 2022. Inclusion and exclusion criteria were used for selection. We collected information from studies to compare the effects of 20 exercise interventions on patients with chronic low back pain. Results: This study included 75 randomized controlled trials (RCTs) with 5,254 participants. Network meta-analysis results showed that tai chi [standardized mean difference (SMD), -2.11; 95% CI, -3.62 to -0.61], yoga (SMD, -1.76; 95% CI -2.72 to -0.81), Pilates exercise (SMD, -1.52; 95% CI, -2.68, to -0.36), and sling exercise (SMD, -1.19; 95% CI, -2.07 to -0.30) showed a better pain improvement than conventional rehabilitation. Tai chi (SMD, -2.42; 95% CI, -3.81 to -1.03) and yoga (SMD, -2.07; 95% CI, -2.80 to -1.34) showed a better pain improvement than no intervention provided. Yoga (SMD, -1.72; 95% CI, -2.91 to -0.53) and core or stabilization exercises (SMD, -1.04; 95% CI, -1.80 to -0.28) showed a better physical function improvement than conventional rehabilitation. Yoga (SMD, -1.81; 95% CI, -2.78 to -0.83) and core or stabilization exercises (SMD, -1.13; 95% CI, -1.66 to -0.59) showed a better physical function improvement than no intervention provided. Conclusion: Compared with conventional rehabilitation and no intervention provided, tai chi, toga, Pilates exercise, sling exercise, motor control exercise, and core or stabilization exercises significantly improved CLBP in patients. Compared with conventional rehabilitation and no intervention provided, yoga and core or stabilization exercises were statistically significant in improving physical function in patients with CLBP. Due to the limitations of the quality and quantity of the included studies, it is difficult to make a definitive recommendation before more large-scale and high-quality RCTs are conducted.

Multi-omics analysis of an in vitro photoaging model and protective effect of umbilical cord mesenchymal stem cell-conditioned medium.

BACKGROUND: Skin ageing caused by long-term ultraviolet (UV) irradiation is a complex biological process that involves multiple signalling pathways. Stem cell-conditioned media is believed to have anti-ageing effects on the skin. The purpose of this study was to explore the biological effects of UVB irradiation and anti-photoaging effects of human umbilical cord mesenchymal stem cell-conditioned medium (hUC-MSC-CM) on HaCaT cells using multi-omics analysis with a novel cellular photoaging model. METHODS: A cellular model of photoaging was constructed by irradiating serum-starved HaCaT cells with 20 mJ/cm2 UVB. Transcriptomics and proteomics analyses were used to explore the biological effects of UVB irradiation on photoaged HaCaT cells. Changes in cell proliferation, apoptosis, and migration, the cell cycle, and expression of senescence genes and proteins were measured to assess the protective effects of hUC-MSC-CM in the cellular photoaging model. RESULTS: The results of the multi-omics analysis revealed that UVB irradiation affected various biological functions of cells, including cell proliferation and the cell cycle, and induced a senescence-associated secretory phenotype. hUC-MSC-CM treatment reduced cell apoptosis, inhibited G1 phase arrest in the cell cycle, reduced the production of reactive oxygen species, and promoted cell motility. The qRT-PCR results indicated that MYC, IL-8, FGF-1, and EREG were key genes involved in the anti-photoaging effects of hUC-MSC-CM. The western blotting results demonstrated that C-FOS, C-JUN, TGFß, p53, FGF-1, and cyclin A2 were key proteins involved in the anti-photoaging effects of hUC-MSC-CM. CONCLUSION: Serum-starved HaCaT cells irradiated with 20 mJ/cm2 UVB were used to generate an innovative cellular photoaging model, and hUC-MSC-CM demonstrates potential as an anti-photoaging treatment for skin.

CRISPR/Cas9 nanoeditor of double knockout large fragments of E6 and E7 oncogenes for reversing drugs resistance in cervical cancer.

Drug resistance of tumor cells is always a headache problem in clinical treatment. In order to combat chemotherapy-resistance in cervical cancer and improve treatment effect, we design a CRISPR/Cas9 nanoeditor to knock out two key oncogenes E6 and E7 that lead to drug tolerance. Meanwhile, the deletion of these two oncogenes can effectively reactivate p53 and pRB signaling pathways that inhibit the growth of tumor cells. Our results demonstrated the nanoeditor could simultaneously delete two oncogenes, and the size of DNA fragments knocked out reaches an unprecedented 563 bp. After the preparation of cationic liposomes combined with chemotherapy drug docetaxel (DOC), this nanosystem can significantly inhibit the drug tolerance of cancer cells and improve the therapeutic effect of cervical cancer. Therefore, this study provides a promising strategy for the treatment of cervical cancer by combining chemotherapy and double-target gene therapy. This strategy can also be applied in other disease models to customize personalized anti-tumor strategies by simply changing chemotherapy drugs and targeted genes.

Effects of different aerobic exercise training on glycemia in patients with type 2 diabetes: A protocol for systematic review and meta analysis.

BACKGROUND: Type 2 diabetes is an emergent worldwide health crisis, and rates are growing globally. Aerobic exercise is an essential measure for patients with diabetes, which has the advantages of flexible time and low cost. Aerobic exercise is a popular method to reduce blood glucose. Due to the lack of randomized trials to compare the effects of various aerobic exercises, it is difficult to judge the relative efficacy. Therefore, we intend to conduct a network meta-analysis to evaluate these aerobic exercises. METHODS: According to the retrieval strategies, randomized controlled trials on different aerobic exercise training will be obtained from China National Knowledge Infrastructure, WanFang, SinoMed, PubMed, Web of Science, EMBASE, and Cochrane Library, regardless of publication date or language. Studies were screened based on inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the literature. The network meta-analysis will be performed in Markov Chain Monte Carlo method and carried out with Stata14 and OpenBUGS software. Ultimately, the evidentiary grade for the results will be evaluated. RESULTS: Eighteen literatures with a total of 1134 patients were included for the meta-analysis. In glycemia assessment, Tennis (standard mean difference = 3.59, credible interval 1.52, 5.65), had significantly better effects than the named control group. Tennis (standard mean difference = 3.50, credible interval 1.05, 5.59), had significantly better effects than the named Taiji group. CONCLUSION: All together, these results suggest that tennis may be the best way to improve blood glucose in patients with type 2 diabetes. This study may provide an excellent resource for future control glycemia and may also serve as a springboard for creative undertakings as yet unknown.

Enterovirus D68 Protease 2Apro Targets TRAF3 To Subvert Host Innate Immune Responses.

Human enterovirus D68 (EV-D68) has received considerable attention recently as a global reemergent pathogen because it causes severe respiratory tract infections and acute flaccid myelitis (AFM). The nonstructural protein 2A protease (2Apro) of EVs, which functions in the cleavage of host proteins, comprises a pivotal part of the viral immune evasion process. However, the pathogenic mechanism of EV-D68 is not fully understood. In this study, we found that EV-D68 inhibited antiviral type I interferon responses by cleaving tumor necrosis factor receptor-associated factor 3 (TRAF3), which is the key factor for type I interferon production. EV-D68 inhibited Sendai virus (SEV)-induced interferon regulatory factor 3 (IRF3) activation and beta interferon (IFN-ß) expression in HeLa and HEK293T cells. Furthermore, we demonstrated that EV-D68 and 2Apro were able to cleave the C-terminal region of TRAF3 in HeLa and HEK293T cells, respectively. A cysteine-to-alanine substitution at amino acid 107 (C107A) in the 2Apro protease resulted in the loss of cleavage activity to TRAF3, and mutation of glycine at amino acid 462 to alanine (G462A) in TRAF3 conferred resistance to 2Apro These results suggest that control of TRAF3 by 2Apro may be a mechanism EV-D68 utilizes to subvert host innate immune responses.IMPORTANCE Human enterovirus 68 (EV-D68) has received considerable attention recently as a global reemergent pathogen because it causes severe respiratory tract infections and acute flaccid myelitis. The nonstructural protein 2A protease (2Apro) of EV, which functions in cleavage of host proteins, comprises an essential part of the viral immune evasion process. However, the pathogenic mechanism of EV-D68 is not fully understood. Here, we show for the first time that EV-D68 inhibited antiviral type I interferon responses by cleaving tumor necrosis factor receptor-associated factor 3 (TRAF3). Furthermore, we identified the key cleavage site in TRAF3. Our study may suggest a new mechanism by which the 2Apro of EV facilitates subversion of host innate immune responses. These findings increase our understanding of EV-D68 infection and may help identify new antiviral targets against EV-D68.

The complete plastome sequence of a subtropical tree Pyrus betulaefolia (Rosaceae).

The genus Pyrus, comprising several popular fruit crops worldwide, includes over 30 tree species. Here we determined the complete plastid genome sequence of Pyrus betulaefolia. The plastome consists of 160,184 bp, including a pair of inverted repeats (IRs) with a length of 26,384 bp separated by a large single-copy region (LSC) and a small single-copy region (SSC) of 88,121 bp and 19,295 bp, respectively. Further phylogenetic analyze was conducted using 11 complete plastid genomes of Rosaceae with KVM + F + I model, which supports Pyrus betulaefolia as a sister to all other eight Pyrus taxa with published plastomes.

Bio-Inorganic Hybrid Nongenetically Modified Viruses as an Immune Agonist for Systemic Elimination of Cancer Cells.

Microbial-based cancer therapy is nowadays considered as an interesting approach, especially with viruses which are attracting more attention owing to their simple structure and nanoscale. However, because of the need for cumbersome genetic modification and poor biosafety, its application is seriously limited. Here, nonpathogenic natural Sendai viruses (SEVs) are used as an alternative immune agonist after being mineralized by calcium ions. Both in vitro and in vivo studies indicated that virus-inorganic hybrids can effectively excite antigen-presenting cells (APCs). Then, the tumor antigens were released in large amounts by photothermal damage. Meanwhile, these released antigens were presented to lymph nodes to mature antitumor T lymphocytes via the peritumoral APCs previously recruited by the SEV. Our results demonstrated that even after administration at one point, the nanohybrids could still effectively stimulate systemic antitumor immune response to suppress the potential cancer metastatic spread. The bio-inorganic hybrid nongenetically modified virus-inorganic nanocomposites might serve as an alternative strategy for synergistic immune therapy.