Combined transcriptomic and metabolomic analysis revealed that pH changes affected the expression of carbohydrate and ribosome biogenesis-related genes in Aspergillus niger SICU-33.

The process of carbohydrate metabolism and genetic information transfer is an important part of the study on the effects of the external environment on microbial growth and development. As one of the most significant environmental parameters, pH has an important effect on mycelial growth. In this study, the effects of environmental pH on the growth and nutrient composition of Aspergillus niger (A. niger) filaments were determined. The pH values of the medium were 5, 7, and 9, respectively, and the molecular mechanism was further investigated by transcriptomics and metabolomics methods. The results showed that pH 5 and 9 significantly inhibited filament growth and polysaccharide accumulation of A. niger. Further, the mycelium biomass of A. niger and the crude polysaccharide content was higher when the medium's pH was 7. The DEGs related to ribosome biogenesis were the most abundant, and the downregulated expression of genes encoding XRN1, RRM, and RIO1 affected protein translation, modification, and carbohydrate metabolism in fungi. The dynamic changes of pargyline and choline were in response to the oxidative metabolism of A. niger SICU-33. The ribophorin_I enzymes and DL-lactate may be important substances related to pH changes during carbohydrate metabolism of A.niger SICU-33. The results of this study provide useful transcriptomic and metabolomic information for further analyzing the bioinformatic characteristics of A. niger and improving the application in ecological agricultural fermentation.

The association between systemic immune-inflammation index and cardiotoxicity related to 5-Fluorouracil in colorectal cancer.

BACKGROUND AND AIMS: The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. METHODS: The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. RESULTS: Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 109/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 109/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 109/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). CONCLUSION: Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.

A-to-I RNA co-editing predicts clinical outcomes and is associated with immune cells infiltration in hepatocellular carcinoma.

Aberrant RNA editing has emerged as a pivotal factor in the pathogenesis of hepatocellular carcinoma (HCC), but the impact of RNA co-editing within HCC remains underexplored. We used a multi-step algorithm to construct an RNA co-editing network in HCC, and found that HCC-related RNA editings are predominantly centralized within the network. Furthermore, five pairs of risk RNA co-editing events were significantly correlated with the overall survival in HCC. Based on presence of risk RNA co-editings resulted in the categorization of HCC patients into high-risk and low-risk groups. Disparities in immune cell infiltrations were observed between the two groups, with the high-risk group exhibiting a greater abundance of exhausted T cells. Additionally, seven genes associated with risk RNA co-editing pairs were identified, whose expression effectively differentiates HCC tumor samples from normal ones. Our research offers an innovative perspective on the etiology and potential therapeutics for HCC.

Effects of hesperidin on the histological structure, oxidative stress, and apoptosis in the liver and kidney induced by NiCl2.

The aim of this study was to investigate the effect of hesperidin on the liver and kidney dysfunctions induced by nickel. The mice were divided into six groups: nickel treatment with 80 mg/kg, 160 mg/kg, 320 mg/kg hesperidin groups, 0.5% CMC-Na group, nickel group, and blank control group. Histopathological techniques, biochemistry, immunohistochemistry, and the TUNEL method were used to study the changes in structure, functions, oxidative injuries, and apoptosis of the liver and kidney. The results showed that hesperidin could alleviate the weight loss and histological injuries of the liver and kidney induced by nickel, and increase the levels of lactate dehydrogenase (LDH), alanine aminotransferase (GPT), glutamic oxaloacetic transaminase (GOT) in liver and blood urea nitrogen (BUN), creatinine (Cr) and N-acetylglucosidase (NAG) in kidney. In addition, hesperidin could increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) in the liver and kidney, decrease the content of malondialdehyde (MDA) and inhibit cell apoptosis. It is suggested that hesperidin could help inhibit the toxic effect of nickel on the liver and kidney.

The facilitators and barriers to implementing virtual visits in intensive care units: A mixed-methods systematic review.

BACKGROUND: Visitation has a positive effect on patients and families, yet, it can disrupt intensive care unit (ICU) care and increase the risk of patient infections, which previously favoured face-to-face visits. The coronavirus disease 2019 (COVID-19) pandemic has raised the importance of virtual visits and led to their widespread adoption globally, there are still many implementation barriers that need to be improved. Therefore, this review aimed to explore the use of ICU virtual visit technology during the COVID-19 pandemic and the barriers and facilitators of virtual visits to improve virtual visits in ICUs. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, six databases (CINAHL, China National Knowledge Infrastructure [CNKI], PubMed, Cochrane, VIP and Wang Fang databases) were searched for empirical studies published between 1 January 2020 and 22 October 2023. Studies that investigated and reported barriers to and facilitators of implementing virtual visits in ICUs during the COVID-19 pandemic were included. Evidence from the included studies was identified and thematically analysed using Thomas and Harden's three-step approach. Study quality was appraised with the Mixed-Methods Appraisal Tool. RESULTS: A total of 6770 references were screened, of which 35 studies met the inclusion criteria after a full-text review. Eight main barriers to virtual visits use were identified: technical difficulties; insufficient resources; lack of physical presence and nonverbal information; low technical literacy; differences in families' perceptions of visual cues; privacy and ethics issues; inequitable access and use of virtual visit technology; and lack of advance preparation. Four facilitating factors of virtual visit use were identified: providing multidimensional professional support; strengthening coordination services; understanding the preferences of patients and their families; and enhancing privacy and security protection. In the quality appraisal of 35 studies, 12 studies were rated as low, five as medium and 18 as high methodological quality. CONCLUSION: This review identified key facilitating factors and barriers to ICU virtual visits, which can foster the development of infrastructure, virtual visiting workflows, guidelines, policies and visiting systems to improve ICU virtual visiting services. Further studies are necessary to identify potential solutions to the identified barriers.

Research progress on knowledge-attitude-practice of VTE prevention in hospitalized patients: A review.

This study analyzes and summarizes the assessment tools, current situation, and influencing factors of venous thromboembolism (VTE) prevention knowledge, attitudes, and practices (KAP) among patients. This study aimed to provide a reference basis for developing targeted health education plans and intervention strategies for patients to improve their knowledge and beliefs concerning VTE prevention. This study aimed to increase the implementation rate of VTE prevention measures and ultimately reduce the incidence of VTE.The current studies found that the factors influencing knowledge, attitude, and practice of VTE prevention in hospitalized patients include demographic factors (age, sex, education level, occupation), disease-related factors (treatment stage, injury site, and wards), and other factors (receiving VTE-related knowledge education and having medical workers at home).

Unraveling colorectal cancer prevention: The vitamin D - gut flora - immune system nexus.

Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.

Renal anastomosing hemangioma following partial nephrectomy for renal cell carcinoma: A case report.

BACKGROUND: Renal anastomosing hemangioma (AH) is a rare benign vascular tumor characterized by unique histopathological features. CASE SUMMARY: We report a highly unusual case of renal AH. A male patient had undergone partial nephrectomy for clear cell carcinoma of the kidney four years prior. A follow-up computed tomography scan in the third postoperative year revealed a new mass near the surgical site on the same side of the kidney, raising suspicions of tumor recurrence. However, the characteristics on contrast-enhanced magnetic resonance imaging and ultrasonography were more consistent with those of a benign lesion. The patient strongly insisted on undergoing surgery due to concerns about the possibility of renal cancer recurrence. Postoperative pathology confirmed the diagnosis of renal AH. CONCLUSION: This case report presents the imaging features of a patient with rare renal AH and a history of renal clear cell carcinoma, providing broader insights into the differential diagnosis of new lesions after surgery for renal cell carcinoma.

MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression.

BACKGROUND: Mitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non-small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear. METHODS: The detection of mRNA and protein of MRPL35, ubiquitin-specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT-PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α-ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis. RESULTS: MRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells. CONCLUSION: MRPL35 expression was stabilized by USP39-induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.

Plasma metabolomics of immune-related adverse events for patients with lung cancer treated with PD-1/PD-L1 inhibitors.

BACKGROUND: Metabolomics has the characteristics of terminal effects and reflects the physiological state of biological diseases more directly. Several current biomarkers of multiple omics were revealed to be associated with immune-related adverse events (irAEs) occurrence. However, there is a lack of reliable metabolic biomarkers to predict irAEs. This study aims to explore the potential metabolic biomarkers to predict risk of irAEs and to investigate the association of plasma metabolites level with survival in patients with lung cancer receiving PD-1/PD-L1 inhibitor treatment. METHODS: The study collected 170 plasmas of 85 patients with lung cancer who received immune checkpoint inhibitors (ICIs) treatment. 58 plasma samples of 29 patients with irAEs were collected before ICIs treatment and at the onset of irAEs. 112 plasma samples of 56 patients who did not develop irAEs were collected before ICIs treatment and plasma matched by treatment cycles to onset of irAEs patients. Untargeted metabolomics analysis was used to identify the differential metabolites before initiating ICIs treatment and during the process that development of irAEs. Kaplan-Meier curves analysis was used to detect the associations of plasma metabolites level with survival of patients with lung cancer. RESULTS: A total of 24 differential metabolites were identified to predict the occurrence of irAEs. Baseline acylcarnitines and steroids levels are significantly higher in patients with irAEs, and the model of eight acylcarnitine and six steroid metabolites baseline level predicts irAEs occurrence with area under the curve of 0.91. Patients with lower concentration of baseline decenoylcarnitine(AcCa(10:1) 2, decenoylcarnitine(AcCa(10:1) 3 and hexanoylcarnitine(AcCa(6:0) in plasma would have better overall survival (OS). Moreover, 52 differential metabolites were identified related to irAEs during ICIs treatment, dehydroepiandrosterone sulfate, corticoserone, cortisol, thyroxine and sphinganine 1-phaosphate were significantly decreased in irAEs group while oxoglutaric acid and taurocholic acid were significantly increased in irAEs group. CONCLUSIONS: High levels of acylcarnitines and steroid hormone metabolites might be risk factor to development of irAEs, and levels of decenoylcarnitine (AcCa(10:1) 2, decenoylcarnitine (AcCa(10:1) 3 and hexanoylcarnitine (AcCa(6:0) could be used to predict OS for patients with lung cancer received ICIs treatment.

Neuropilin-1 is a novel host factor modulating the entry of hepatitis B virus.

BACKGROUND & AIMS: Sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for hepatitis B virus (HBV). However, hepatocytes expressing NTCP exhibit varying susceptibilities to HBV infection. This study aimed to investigate whether other host factors modulate the process of HBV infection. METHODS: Liver biopsy samples obtained from children with hepatitis B were used for single-cell sequencing and susceptibility analysis. Primary human hepatocytes, HepG2-NTCP cells, and human liver chimeric mice were used to analyze the effect of candidate host factors on HBV infection. RESULTS: Single-cell sequencing and susceptibility analysis revealed a positive correlation between neuropilin-1 (NRP1) expression and HBV infection. In the HBV-infected cell model, NRP1 overexpression before HBV inoculation significantly enhanced viral attachment and internalization, and promoted viral infection in the presence of NTCP. Mechanistic studies indicated that NRP1 formed a complex with LHBs and NTCP. The NRP1 b domain mediated its interaction with conserved arginine residues at positions 88 and 92 in the preS1 domain of the HBV envelope protein LHBs. This NRP1-preS1 interaction subsequently promoted the binding of preS1 to NTCP, facilitating viral infection. Moreover, disruption of the NRP1-preS1 interaction by the NRP1 antagonist EG00229 significantly attenuated the binding affinity between NTCP and preS1, thereby inhibiting HBV infection both in vitro and in vivo. CONCLUSIONS: Our findings indicate that NRP1 is a novel host factor for HBV infection, which interacts with preS1 and NTCP to modulate HBV entry into hepatocytes. IMPACT AND IMPLICATIONS: HBV infection is a global public health problem, but the understanding of the early infection process of HBV remains limited. Through single-cell sequencing, we identified a novel host factor, NRP1, which modulates HBV entry by interacting with HBV preS1 and NTCP. Moreover, antagonists targeting NRP1 can inhibit HBV infection both in vitro and in vivo. This study could further advance our comprehension of the early infection process of HBV.

Source and level of dietary iron influence semen quality by affecting inflammation, oxidative stress and iron utilization levels in boars.

BACKGROUND: Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15-21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. RESULTS: 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters. CONCLUSIONS: Dietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars.

Exploring the pharmacological mechanisms of the flower of Rhododendron molle in rheumatoid arthritis rats based on metabolomics integrated network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, the flower of Rhododendron molle G. Don (RMF) is record in the Chinese pharmacopoeia, and is commonly utilized for treating rheumatoid arthritis (RA) in clinical practice. However, its precise mechanisms necessitate further exploration. AIM OF THE STUDY: To expound the effective components, targets, metabolites, and pathways participated in RMF's anti-RA effects by metabolomics integrated network pharmacology. MATERIALS AND METHODS: CIA rats were intragastric administered RMF for 2 weeks, following which the therapeutic effects were comprehensively evaluated. Serum metabolomics was adopted to investigate the differential metabolites (DEMs). UHPLC-Q-Exactive-MS method was applied to identify the components of RMF, and then network pharmacology was utilize to select the component-RA-targets. Molecular docking and Western blotting were utilized to validate the key targets. RESULTS: RA symptoms were alleviated by RMF through the inhibition secretion of pro-inflammatory factors IL-1ß, IL-6 and TNF-α, along with relief in bone destruction observed in CIA rats. Four targets, namely AKR1B1, TPH1, CYP1A1, and CYP1A2, were identified, along with their corresponding metabolites, namely D-glucose, D-mannose, L-tryptophan, 11-deoxycorticosterone, and 17α-hydroxyprogesterone. These were found to be involved in three key metabolic pathways: steroid hormone biosynthesis, tryptophan metabolism, and galactose metabolism. Additionally, five significant anti-RA active components were identified from RMF, including Rhodojaponin (Rj)-Ⅱ, Rj-Ⅲ, Rj-Ⅴ, Rj-Ⅵ, and quercetin. CONCLUSIONS: The anti-RA mechanisms of RMF were investigated in this study, focusing on active components, upstream targets, and downstream metabolites. These findings lay a foundation for the clinical practice and drug development of RMF.

Cinnamaldehyde alleviates aspirin-induced gastric mucosal injury by regulating pi3k/akt pathway-mediated apoptosis, autophagy and ferroptosis.

BACKGROUND: Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there is an urgent need to find safe and effective drugs to prevent gastric mucosal injury due to NSAIDs. Cinnamaldehyde (CA) is a bioactive compound extracted from the rhizome of cinnamon and has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, and antioxidant activities. However, the potential pharmacological effect of CA on gastric mucosal injury remains unknown. PURPOSE: The aim of this study was to investigate the protective effects of CA on aspirin-induced gastric mucosal injury and to explore its mechanism of action METHODS: The effect of CA on gastric mucosal injury was investigated in vitro and in vivo, in vitro mouse model of gastric mucosal injury induced by aspirin, in vitro model of GES-1 cell injury by aspirin and Erastin. The mechanism of action of CA was determined using Transcriptomics and bioinformatics. RESULTS: CA exerted its protective effects against gastric mucosal injury by modulating the downstream targets, including mTOR, GSK3ß, and NRF2, via the PI3K/AKT signaling pathway to inhibit autophagy, apoptosis, and ferroptosis in the gastric epithelial cells. Further cellular experiments confirmed that the PI3K/AKT pathway was a key target for CA against gastric mucosal injury. CONCLUSION: This study provides the first evidence of CA, an active compound in cinnamon, possessing therapeutic potential in preventing and treating gastric mucosal injury, with its mechanism involving the regulation of apoptosis, autophagy, and ferroptosis in gastric epithelial cells mediated by the PI3K/AKT signaling pathway.

The Effect of Bifidobacterium animalis subsp. lactis MN-Gup on Glucose Metabolism, Gut Microbiota, and Their Metabolites in Type 2 Diabetic Mice.

Probiotics have garnered increasing attention as a potential therapeutic approach for type 2 diabetes mellitus (T2DM). Previous studies have confirmed that Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) could stimulate the secretion of glucagon-like peptide-1 (GLP-1) in NCI-H716 cells, but whether MN-Gup has a hypoglycemic effect on T2DM in vivo remains unclear. In this study, a T2DM mouse model was constructed, with a high-fat diet and streptozotocin in mice, to investigate the effect of MN-Gup on diabetes. Then, different doses of MN-Gup (2 × 109 CFU/kg, 1 × 1010 CFU/kg) were gavaged for 6 weeks to investigate the effect of MN-Gup on glucose metabolism and its potential mechanisms. The results showed that a high-dose of MN-Gup significantly reduced the fasting blood glucose (FBG) levels and homeostasis model assessment-insulin resistance (HOMA-IR) of T2DM mice compared to the other groups. In addition, there were significant increases in the short-chain fatty acids (SCFAs), especially acetate, and GLP-1 levels in the MN-Gup group. MN-Gup increased the relative abundance of Bifidobacterium and decreased the number of Escherichia-Shigella and Staphylococcus. Moreover, the correlation analysis revealed that Bifidobacterium demonstrated a significant positive correlation with GLP-1 and a negative correlation with the incremental AUC. In summary, this study demonstrates that Bifidobacterium animalis subsp. lactis MN-Gup has significant hypoglycemic effects in T2DM mice and can modulate the gut microbiota, promoting the secretion of SCFAs and GLP-1.

Development of the neonatal pain response variable set: a mixed methods consensus process.

While over 40 neonatal pain assessment scales have been published, owing to a lack of consensus and standardized metrics, there are more than 100 assessment indicators with varying descriptors and quality differences. This study aims to reach a consensus on optimal and comprehensive variables for neonatal pain assessment, leading to the development of a multidimensional neonatal pain response variable set. This study consisted of three phases: (1) A literature review was conducted to identify influencing factors and assessment indicators of neonatal pain response. (2) Panel meetings involving neonatal healthcare professionals evaluated and screened factors and indicators to develop an initial draft of the variable set. (3) Through two rounds of Delphi study achieved consensus, and determined the neonatal pain response variable set. Through a literature review and a panel meeting, the identified factors and indicators were categorized into contextual, physiological, and behavioral variables, forming an initial draft of the variable set. Sixteen professionals participated in two rounds of the Delphi study, with response rates exceeding 70%, and authority coefficients surpassing 0.7 in both rounds. The final iteration of the variable set includes 9 contextual variables, 2 physiological variables, and 5 behavioral variables.   Conclusion: Neonatal pain response variable set developed in this study is scientific, comprehensive, and multidimensional, aligning with the characteristics of neonatal pain response and clinically applicable. The inclusion of contextual variables enhances the ability to confront the complexity of clinical environments and individual differences. It can provide a practical and theoretical basis for clinical research on neonatal pain assessment. What is Known: • Neonatal pain assessment relies on scales used by healthcare professionals currently. But there is no "gold standard" for neonatal pain assessment. • While over 40 neonatal pain assessment scales have been published, owing to a lack of consensus and standardized metrics, there are more than 100 assessment indicators with varying descriptors and quality differences. Most of scales overlook the clinical environment complexity individual differences in pain responses, diminishing the accuracy and applicability. What is New: • In addition to the commonly used physiological and behavioral variables in the scales, we have incorporated contextual variables to better address the complexity of clinical environments and individual differences in pain responses. • Through an evidence-based approach, developed a neonatal pain response variable set comprising 9 contextual variables, 2 physiological variables, and 5 behavioral variables.

Enhancing hospice care with psychological support and a nomogram to predict delirium in patients with advanced solid tumors.

To assesses the impact of integrating hospice care with psychological interventions on patient well-being and to introduce a predictive nomogram model for delirium that incorporates clinical and psychosocial variables, thereby improving the accuracy in hospice care environments. Data from 381 patients treated from September 2018 to February 2023 were analyzed. The patients were divided into a control group (n=177, receiving standard care) and an experimental group (n=204, receiving combined hospice care and psychological interventions) according to the treatment modality. The duration of care extended until the patient's discharge from the hospital or death. The experimental group demonstrated significant improvements in emotional well-being and a lower incidence of delirium compared to the control group. Specifically, emotional well-being assessments revealed marked improvements in the experimental group, as evidenced by lower scores on the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) post-intervention. The nomogram model, developed using logistic regression based on clinical characteristics, effectively predicted the risk of delirium in patients with advanced cancer. Significant predictors in the model included ECOG score ≥3, Palliative Prognostic Index score ≥6, opioid usage, polypharmacy, infections, sleep disorders, organ failure, brain metastases, electrolyte imbalances, activity limitations, pre-care SAS score ≥60, pre-care SDS score ≥63, and pre-care KPS score ≥60. The model's predictive accuracy was validated, showing AUC values of 0.839 for the training cohort and 0.864 for the validation cohort, with calibration and Decision Curve Analysis (DCA) confirming its clinical utility. Integrating hospice care with psychological interventions not only significantly enhanced the emotional well-being of advanced cancer patients but also reduced the actual incidence of delirium. This approach, offering a valuable Nomogram model for precise care planning and risk management, underscores the importance of integrated, personalized care strategies in advanced cancer management.

Development and application of a risk nomogram for the prediction of risk of carbapenem-resistant Acinetobacter baumannii infections in neuro-intensive care unit: a mixed method study.

OBJECTIVE: This study aimed to develop and apply a nomogram with good accuracy to predict the risk of CRAB infections in neuro-critically ill patients. In addition, the difficulties and expectations of application such a tool in clinical practice was investigated. METHODS: A mixed methods sequential explanatory study design was utilized. We first conducted a retrospective study to identify the risk factors for the development of CRAB infections in neuro-critically ill patients; and further develop and validate a nomogram predictive model. Then, based on the developed predictive tool, medical staff in the neuro-ICU were received an in-depth interview to investigate their opinions and barriers in using the prediction tool during clinical practice. The model development and validation is carried out by R. The transcripts of the interviews were analyzed by Maxqda. RESULTS: In our cohort, the occurrence of CRAB infections was 8.63% (47/544). Multivariate regression analysis showed that the length of neuro-ICU stay, male, diabetes, low red blood cell (RBC) count, high levels of procalcitonin (PCT), and number of antibiotics ≥ 2 were independent risk factors for CRAB infections in neuro-ICU patients. Our nomogram model demonstrated a good calibration and discrimination in both training and validation sets, with AUC values of 0.816 and 0.875. Additionally, the model demonstrated good clinical utility. The significant barriers identified in the interview include "skepticism about the accuracy of the model", "delay in early prediction by the indicator of length of neuro-ICU stay", and "lack of a proper protocol for clinical application". CONCLUSIONS: We established and validated a nomogram incorporating six easily accessed indicators during clinical practice (the length of neuro-ICU stay, male, diabetes, RBC, PCT level, and the number of antibiotics used) to predict the risk of CRAB infections in neuro-ICU patients. Medical staff are generally interested in using the tool to predict the risk of CRAB, however delivering clinical prediction tools in routine clinical practice remains challenging.

Variations in the LINGO2 and GLIS3 Genes and Gene-Environment Interactions Increase Gestational Diabetes Mellitus Risk in Chinese Women.

Gestational diabetes mellitus (GDM) has been found to be a common complication in pregnant women, known to escalate the risk of negative obstetric outcomes. In our study, we genotyped 1,566 Chinese pregnant women for two single nucleotide polymorphisms (SNPs) in the LINGO2 gene and one SNP in the GLIS3 gene, utilizing targeted next-generation sequencing. The impact of two interacting genes, and the interaction of genes with the environment─including exposure to particulate matter (PM2.5), ozone (O3), and variations in prepregnancy body mass index (BMI)─on the incidence of GDM were analyzed using logistic regression. Our findings identify the variants LINGO2 rs10968576 (P = 0.022, OR = 1.224) and rs1412239 (P = 0.018, OR = 1.231), as well as GLIS3 rs10814916 (P = 0.028, OR = 1.172), as risk mutations significantly linked to increased susceptibility to GDM. Further analysis underscores the crucial role of gene-gene and gene-environment interactions in the development of GDM among Chinese women (P < 0.05). Particularly, the individuals carrying the rs10968576 G-rs1412239 G-rs10814916 C haplotype exhibit increased susceptibility to GDM during the prepregnancy period when interacting with PM2.5, O3, and BMI (P = 8.004 × 10-7, OR = 1.206; P = 6.3264 × 10-11, OR = 1.280; P = 9.928 × 10-7, OR = 1.334, respectively). In conclusion, our research emphasizes the importance of the interaction between specific gene variations─LINGO2 and GLIS3─and environmental factors in influencing GDM risk. Notably, we found significant associations between these gene variations and GDM risk across various environmental exposure periods.