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.

Effects of Trichinella spiralis and its serine protease inhibitors on autophagy of host small intestinal cells.

In eukaryotes, autophagy is induced as an innate defense mechanism against pathogenic microorganisms by self-degradation. Although trichinellosis is a foodborne zoonotic disease, there are few reports on the interplay between Trichinella spiralissurvival strategies and autophagy-mediated host defense. Therefore, this study focused on the association between T. spiralis and autophagy of host small intestinal cells. In this study, the autophagy-related indexes of host small intestinal cells after T. spiralis infection were detected using transmission electron microscopy, hematoxylin and eosin staining, immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting. The results showed that autophagosomes and autolysosomes were formed in small intestinal cells, intestinal villi appeared edema, epithelial compactness was decreased, microtubule-associated protein 1A/1B-light chain 3B (LC3B) was expressed in lamina propria stromal cells of small intestine, and the expression of autophagy-related genes and proteins was changed significantly, indicating that T. spiralis induced autophagy of host small intestinal cells. Then, the effect of T. spiralis on autophagy-related pathways was explored by Western blotting. The results showed that the expression of autophagy-related pathway proteins was changed, indicating that T. spiralis regulated autophagy by affecting autophagy-related pathways. Finally, the roles of T. spiralis serine protease inhibitors (TsSPIs), such as T. spiralis Kazal-type SPI (TsKaSPI) and T. spiralis Serpin-type SPI (TsAdSPI), were further discussed in vitro and in vivo experiments. The results revealed that TsSPIs induced autophagy by influencing autophagy-related pathways, and TsAdSPI has more advantages. Overall, our results indicated that T. spiralis induced autophagy of host small intestinal cells, and its TsSPIs play an important role in enhancing autophagy flux by affecting autophagy-related pathways. These findings lay a foundation for further exploring the pathogenesis of intestinal dysfunction of host after T. spiralis infection, and also provide some experimental and theoretical basis for the prevention and treatment of trichinellosis.

Bacterial Etiology and Antimicrobial Resistance Pattern of Pediatric Bloodstream Infections in Beijing, 2015-2019.

Purpose: Bloodstream infections (BSIs) was an essential cause of morbidity and mortality in children. Empiric broad-spectrum treatment of BSIs may be costly and unable to effectively eliminate the correct pathogenic microbes, resulting in downstream antimicrobial resistance. The purpose was to provide evidence for diagnosis and treatment of bloodstream infections in pediatrics, by revealing the pathogen distribution and antibiotic resistance pattern of BSIs. Methods: In this 5-year study, a total of 2544 pathogenic bacteria stains, isolated from 2368 patients with BSI, were retrospectively analyzed, to define the species distribution and the antimicrobial resistance pattern in Beijing. Results: The most frequently isolated pathogenic bacteria were K. pneumoniae (12.1%), S. aureus (11.5%), E. coli (11.2%), and E. faecium (11.2%). Hematological malignancies were the most common disease among patients with underlying conditions. Methicillin resistance was detected in 30.0% of S. aureus and 81.7% of coagulase-negative Staphylococcus (CoNS), respectively. The detection rates of carbapenem-resistant-E. coli (CRECO) and carbapenem-resistant-K. pneumoniae (CRKPN) were 10.8% and 50.8%, respectively. In terms of 122 isolates of S. pneumonia, 5 isolates (4.1%) were penicillin-resistant Streptococcus pneumoniae (PRSP); meanwhile, 50 isolates (41.0%) were penicillin-intermediate Streptococcus pneumoniae (PISP). Among the non-fermentative gram-negative bacilli isolates, 22.8% and 26.9% of the P. aeruginosa, were resistant to imipenem and meropenem. Furthermore, the resistance rates of A. baumannii to imipenem and meropenem both were 54.5%. Conclusion: In the study, we demonstrated the characteristics of bloodstream infections and antimicrobial susceptibility pattern of pediatrics in Beijing. Gram positive bacteria were the main pathogens of BSIs. CoNS strains presented even higher resistance to multiple antibiotics, including methicillin, than S. aureus. K. pneumoniae and E. coli represent the most common isolated gram-negative bacteria and exhibited high resistance to a variety of antimicrobial agents. Therefore, it was of critical importance to implement appropriate antimicrobial medication according to pathogen distribution and drug susceptibility test.

Characterization of N-Terminal Asparagine Deamidation and Clipping of a Monoclonal Antibody.

This study presents a novel degradation pathway of a human immunoglobulin G (IgG) molecule featuring a light chain N-terminal asparagine. We thoroughly characterize this pathway and investigate its charge profiles using cation exchange chromatography (CEX) and capillary isoelectric focusing (cIEF). Beyond the well-documented asparagine deamidation into isoaspartic acid, aspartic acid, and succinimide intermediate, a previously unreported clipping degradation pathway is uncovered. This newly identified clipped N-terminal IgG variant exhibits a delayed elution in CEX, categorized as a "basic variant", while retaining the same main peak isoelectric point (pI) in cIEF. The influence of temperature and pH on N-terminal asparagine stability is assessed across various stressed conditions. A notable correlation between deamidation percentage and clipped products is established, suggesting a potential hydrolytic chemical reaction underlying the clipping process. Furthermore, the impact of N-terminal asparagine modifications on potency is evaluated through ELISA binding assays, revealing minimal effects on binding affinity. Sequence alignment reveals homology to a human IgG with the germline gene from Immunoglobulin Lambda Variable 6-57 (IGLV6-57), which has implications for amyloid light-chain (AL) amyloidosis. This discovery of the N-terminal clipping degradation pathway contributes to our understanding of immunoglobulin light chain misfolding and amyloid fibril deposition under physiological conditions.

FARSB serves as a novel hypomethylated and immune cell infiltration related prognostic biomarker in hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is a prevalent tumor with high morbidity, and an unfavourable prognosis. FARSB is an aminoacyl tRNA synthase, and plays a key role in protein synthesis in cells. Furthermore, previous reports have indicated that FARSB is overexpressed in gastric tumor tissues and is associated with a poor prognosis and tumorigenesis. However, the function of FARSB in HCC has not been studied. RESULTS: The results showed that FARSB mRNA and protein levels were upregulated in HCC and were closely related to many clinicopathological characteristics. Besides, according to multivariate Cox analysis, high FARSB expression was linked with a shorter survival time in HCC and may be an independent prognostic factor. In addition, the FARSB promoter methylation level was negatively associated with the expression of FARSB. Furthermore, enrichment analysis showed that FARSB was related to the cell cycle. And TIMER analysis revealed that the FARSB expression was closely linked to tumor purity and immune cell infiltration. The TCGA and ICGC data analysis suggested that FARSB expression is greatly related to m6A modifier related genes. Potential FARSB-related ceRNA regulatory networks were also constructed. What's more, based on the FARSB-protein interaction network, molecular docking models of FARSB and RPLP1 were constructed. Finally, drug susceptibility testing revealed that FARSB was susceptible to 38 different drugs or small molecules. CONCLUSIONS: FARSB can serve as a prognostic biomarker for HCC and provide clues about immune infiltration, and m6A modification.

Intervention effects of Trichinella spiralis excretory-secretory antigens on allergic asthma in mice.

Allergic asthma is a chronic, heterogeneous and inflammatory respiratory disease, and there are few medicines at present. An increasing number of studies indicate that Trichinella spiralis (T. spiralis) and its excretory-secretory (ES) antigens are inflammatory modulator. Therefore, this study focused on the effects of T. spiralis ES antigens on allergic asthma. Asthma model was established by sensitizing mice with ovalbumin antigen (OVA) and aluminum hydroxide (Al[OH]3), the asthmatic mice were interfered using T. spiralis 43 kDa protein (Ts43), T. spiralis 49 kDa protein (Ts49), and T. spiralis 53 kDa protein (Ts53), the important components of ES antigens, to establish ES antigens intervention models. Then, asthma symptom changes, weight changes, and lung inflammation of mice were evaluated. The results showed that ES antigens could relieve symptoms, weight loss, and lung inflammation caused by asthma in the mice, and the effect of combined intervention of Ts43, Ts49, and Ts53 was better. Finally, the effects of ES antigens on type 1 helper T (Th1) and type 2 helper T (Th2) immune responses, and the differentiation direction of T lymphocytes in mice were discussed by detecting Th1 and Th2 cell-related factors and the ratio of CD4+/CD8+ T cells. The results suggested that the ratio of CD4+/CD8+ T cells decreased and the ratio of Th1/Th2 cells increased. In conclusion, this study indicated that T. spiralis ES antigens could mitigate allergic asthma in the mice by changing the differentiation direction of CD4+ and CD8+ T cells and regulating the imbalance of Th1/Th2 cells ratio.

The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases.

Morbidity and mortality of cardiovascular diseases (CVDs) are exceedingly high worldwide. Researchers have found that the occurrence and development of CVDs are closely related to intestinal microecology. Imbalances in intestinal microecology caused by changes in the composition of the intestinal microbiota will eventually alter intestinal metabolites, thus transforming the host physiological state from healthy mode to pathological mode. Trimethylamine N-oxide (TMAO) is produced from the metabolism of dietary choline and L-carnitine by intestinal microbiota, and many studies have shown that this important product inhibits cholesterol metabolism, induces platelet aggregation and thrombosis, and promotes atherosclerosis. TMAO is directly or indirectly involved in the pathogenesis of CVDs and is an important risk factor affecting the occurrence and even prognosis of CVDs. This review presents the biological and chemical characteristics of TMAO, and the process of TMAO produced by gut microbiota. In particular, the review focuses on summarizing how the increase of gut microbial metabolite TMAO affects CVDs including atherosclerosis, heart failure, hypertension, arrhythmia, coronary artery disease, and other CVD-related diseases. Understanding the mechanism of how increases in TMAO promotes CVDs will potentially facilitate the identification and development of targeted therapy for CVDs.

A Retrospective Study of the Use of Antibiotic Lock Therapy and Cluster Nursing Management in Infections in Children with Short Bowel Syndrome or Solid Abdominal Tumours Treated with Totally Implantable Venous Access Ports.

Objective: To explore the effective response strategies for infections in infants with short bowel syndrome and solid abdominal tumours, treated with totally implantable venous access ports (TIVAPs). Methods: A total of 210 children who were treated with a TIVAP in our department from 2020 to 2021 were selected for this retrospective study. Eight of these children diagnosed with a catheter-related bloodstream infection were studied in this study; antibiotic lock therapy (ALT) and cluster nursing management were used for treatment, and their effects on the infection outcome were observed. Results: Among the eight children, seven access ports were successfully protected, and one catheter was removed from the right chest wall port due to repeated infection. In this one child, the left side was re-implanted. Conclusion: The use of the ALT combined with cluster-based nursing can better treat infections of TIVAPs, improve the children's healing time, and has important clinical significance in the prevention of complications from the infection and improving the treatment and nursing of the patients diagnosed with these infections.

The antagonistic potential of peanut endophytic bacteria against Sclerotium rolfsii causing stem rot.

Peanut stem rot caused by Sclerotium rolfsii Sacc. is the most common disease of peanut worldwide and has become increasingly serious in recent years. This study is aimed at obtaining peanut endophytic bacteria with high antagonistic/protective effects against peanut stem rot. In total, 45 bacterial strains were isolated from healthy peanut plants from a severely impacted area. Of these, 6 exhibited antagonistic activity against S. rolfsii, including F-1 and R-11 with the most robust activity with an inhibition zone width of 20.25 and 15.49 mm, respectively. These two were identified as Bacillus sp. and Burkholderia sp., respectively, based on morphological, physiological, and biochemical characteristics and 16S rDNA sequencing. To the best of our knowledge, this is the first study to report the Burkholderia sp. antagonistic effect on S. rolfsii as a biological control agent for peanut stem rot. Their culture filtrates potently inhibited the hyphal growth, sclerotial formation, and germination of S. rolfsii. Also, the strain-produced volatile compounds inhibited the fungal growth. Pot experiments showed that F-1 and R-11 significantly reduced the peanut stem rot disease with the efficacy of 77.13 and 64.78%, respectively, which was significantly higher compared with carbendazim medicament (35.22%; P < 0.05). Meanwhile, F-1 and R-11 improved the activity of plant defense enzymes such as phenylalaninase (PAL), polyphenol oxidase (PPO), and peroxidase (POD) enhancing the systemic resistance of the peanut plants. This study demonstrated that Bacillus sp. F-1 and Burkholderia sp. R-11, with a strong antagonistic effect on S. rolfsii, can be potential biocontrol agents for peanut stem rot.

Comprehensive analysis of prognostic value, relationship to cell cycle, immune infiltration and m6A modification of ZSCAN20 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common tumor across the globe with a high mortality rate. ZSCAN20 is a ZNF transcription factor, a key determinant of gene expression. Nonetheless, the mechanism of ZSCAN20 as a potential clinical biomarker and therapeutic target for HCC is not understood. Here, TIMER, TCGA, ICGC databases and immunohistochemical (IHC) and Western Blot found ZSCAN20 mRNA and protein levels were upregulated. Additionally, Kaplan-Meier Plotter, GEPIA and TCGA databases showed high ZSCAN20 expression was related to the short survival time of HCC patients. Multivariate Cox analysis exposed that ZSCAN20 can act as an independent prognostic factor. We observed methylation level of ZSCAN20 was associated with the clinicopathological characteristics and prognosis of HCC patients through UALCAN. Furthermore, enrichment examination exposed functional association between ZSCAN20 and cell cycle, immune infiltration. Functional experiments showed that interference with ZSCAN20 significantly reduced the invasion, migration and proliferation abilities of HCC cells. An immune infiltration analysis showed that ZSCAN20 was associated with immune cells, particularly T cells. The expression of ZSCAN20 was correlated with poor prognosis in the Regulatory T-cell. And Real-Time RT-PCR analysis found interference with ZSCAN20 significantly reduced the expression of some chemokines. Finally, the TCGA and ICGC data analysis suggested that the ZSCAN20 expression was greatly related to m6A modifier related genes. In conclusion, ZSCAN20 can serve as a prognostic biomarker for HCC and provide clues about cell cycle, immune infiltration, and m6A modification.

Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. METHODS: A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. RESULTS: Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 (PBonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 (PBonferroni < 0.001). Amisulpride group had a higher treatment response rate (P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group (PBonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. CONCLUSION: This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974.

ZNF320 is a hypomethylated prognostic biomarker involved in immune infiltration of hepatocellular carcinoma and associated with cell cycle.

Hepatocellular carcinoma (HCC) is one of the most deadly and common malignant cancers around the world, and the prognosis of HCC patients is not optimistic. ZNF320 belongs to Krüppel like zinc finger gene family. However, no studies have focused on the influence of ZNF320 in HCC. We first analyzed ZNF320 expression in HCC by using data from TCGA and ICGC, then conducted a joint analysis with TIMER and UALCAN, and validated by immunohistochemistry in clinical HCC samples. Then we applied UALCAN to explore the correlation between ZNF320 expression and clinicopathological characteristics. Consequently, using Kaplan-Meier Plotter analysis and the Cox regression, we can predict the prognostic value of ZNF320 for HCC patients. Next, the analysis by GO, KEGG, and GSEA revealed that ZNF320 was significantly correlated to cell cycle and immunity. Finally, TIMER and GEPIA analysis verified that ZNF320 expression is closely related to tumor infiltrating immune cells (TIIC), including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. The analysis of the TCGA and ICGC data sets revealed that ZNF320 expression was significantly correlated with m6A related genes (RBMX, YTHDF1, and METTL3). In conclusion, ZNF320 may be a prognostic biomarker related to immunity as a candidate for liver cancer.

MND1 functions as a potential prognostic biomarker associated with cell cycle and immune infiltration in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is a common and invasive subtype of renal tumors, which has poor prognosis and high mortality. MND1 is a meiosis specific protein that participates in the progress of diverse cancers. Nonetheless, its function in KIRC was unclear. Here, TIMER, TCGA, GEO databases and IHC found MND1 expression is upregulated in KIRC, leading to poor overall survival, and MND1 can serve as an independent prognostic factor. Moreover, enrichment analysis revealed the functional relationship between MND1 and cell cycle, immune infiltration. EdU and transwell assays confirmed that MND1 knockdown surely prohibited the proliferation, migration, and invasion of KIRC cells. Additionally, immune analysis showed that MND1 displayed a strong correlation with various immune cells. Interference with MND1 significantly reduces the expression of chemokines. TCGA and GEO databases indicated that MND1 expression is significantly related to two m6A modification related gene (METTL14, IGF2BP3). Finally, the drug sensitivity analysis revealed 7 potentially sensitive drugs for KIRC patients with high MND1 expression. In conclusion, MND1 can be used as a prognostic biomarker for KIRC and provides clues regarding cell cycle, immune infiltrates and m6A. Sensitive drugs may be an effective treatment strategy for KIRC patients with high expression of MND1.

Fear of recurrence in elderly patients with coronary heart disease: the current situation and influencing factors according to a questionnaire analysis.

OBJECTIVE: Fear of recurrence is a common psychosocial sequela among patients with heart disease. Analyses of coronary heart disease, particularly in elderly patients, are relatively rare. This study aimed to investigate the current situation in this context, as well as the influencing fear factors concerning recurrence in elderly patients with coronary heart disease. METHODS: A total of 200 elderly outpatients with coronary heart disease were recruited to participate in this survey from a tertiary hospital in Baoding (China). The questionnaires included items from the Disease Progression Simplified Scale, the Simplified Coping Style Questionnaire, and the Social Support Rating Scale (SSRS). Univariate and multivariate regression analyses were adopted to investigate the influencing factors on the fear of recurrence. RESULTS: The fear of recurrence score in elderly patients with coronary heart disease was (38.46 ± 8.13), among which 119 cases (59.5%) scored higher than 34 points. The SSRS total average score was (34.89 ± 9.83) points. Positive coping style and social support were negatively correlated with the total score of recurrence fear (r = - 0.621, - 0.413, both P < 0.001). There was a positive correlation between negative coping style and the total score of recurrence fear (r = 0.232, P < 0.001). Multiple linear regression analysis showed that the course of the disease, the number of disease recurrence cases, active coping, and social support were relevant factors in fear of recurrence (all P < 0.05). CONCLUSION: The detection rate of fear of recurrence in elderly patients with coronary heart disease was relatively high but could be reduced by active interventions and enhancing social support.

[Distribution Characteristics and Influencing Factors of Germanium in Soil in the Eastern Mountainous Area of the Nanyang Basin].

Based on the land quality geochemical survey results in the southwest cultivated area of Nanyang Basin, the content, spatial distribution, and enrichment characteristics of Ge in surface soil (0-20 cm) and deep soil (150-200 cm) in the eastern mountainous area of Nanyang Basin were studied, and the influencing factors of Ge in the surface soil were analyzed. The results showed that the average ω(Ge) in the surface soil and deep soil were 1.39 mg·kg-1 and 1.45 mg·kg-1, respectively. In the study area, 32.22% of surface soil and 12.77% of surface soil was rich in Ge, and the rich areas of the surface soil Ge were mainly distributed in the metamorphic rock and granite-dominant development areas. The optimal theoretical model of surface soil Ge variogram in the study area was a spherical model, and the nugget effect value was 0.434, indicating that surface soil Ge had moderate spatial correlation due to the joint influence of random factors and structural factors. The enrichment factor showed that 93.61% of Ge sites in the topsoil were mainly affected by natural factors, whereas 6.39% of Ge sites were significantly affected by human factors. The source of Ge in soil in the study area was mainly affected by the parent materials of soil formation, but the enrichment of Ge in surface soil was mainly affected by the Fe, Mn oxides, quartz, and pH in the soil.

Hydrosulfonylation of Alkenes with Sulfonyl Imines via Ir/Cu Dual Photoredox Catalysis.

Sulfonamides exhibit the advantages of wide prevalence, excellent prefunctionalization capability, and broad functional group compatibility. We report here utilizing sulfonyl imines as sulfonyl radical precursors for hydrosulfonylation of activated alkenes via visible-light irradiation. By preinstallation of functional groups into the sulfonamides and subsequent hydrosulfonylation, a variety of complex sulfones were synthesized with good efficiency under Ir/Cu dual photoredox catalysis. Additionally, this protocol expands the research in late-stage N-S bond modification in sulfonamides.

Visible-Light-Mediated Late-Stage Sulfonylation of Anilines with Sulfonamides.

A visible-light-mediated late-stage sulfonylation of anilines with sulfonamides under simple reaction conditions is presented. Various primary or secondary sulfonamides including several pharmaceuticals were incorporated successfully via N-S bond activation and C-H bond sulfonylation. The synthetic utility of this strategy is highlighted by the construction of complex anilines bearing diverse bioactive groups.

The deubiquitinase OTUB1 fosters papillary thyroid carcinoma growth through EYA1 stabilization.

Deubiquitinating enzyme OTU domain-containing ubiquitin aldehyde-binding proteins 1 (OTUB1) has been shown to have an essential role in multiple carcinomas. However, the function of OTUB1 in papillary thyroid cancer (PTC) and the underlying mechanisms regulating PTC cells proliferation remain poorly understood. In this study, OTUB1 was significantly upregulated in papillary thyroid carcinoma tissues and cells. Through in vitro and in vivo experiments, knockdown of OTUB1 suppressed PTC cells growth whereas OTUB1 overexpression enhanced the proliferation ability of PTC cells. Moreover, the eyes absent homologue 1 (EYA1) was recognized as a potential target of OTUB1 through mass spectrometry analysis, and we further verified that EYA1 protein level was positively correlated with OTUB1 expression in PTC cells and clinical samples. Mechanistically, OTUB1 could interact with EYA1 directly and deubiquitinate EYA1 to stabilize it. At last, EYA1 was found to play an essential role in OTUB1-derived PTC cells growth. Overall, our investigation reveals that OTUB1 is a previously unrecognized oncogenic factor in PTC cells proliferation and suggests that OTUB1 might be a novel therapeutic target in PTC.