Achyranthes bidentata polysaccharide ameliorates type 2 diabetes mellitus by gut microbiota-derived short-chain fatty acids-induced activation of the GLP-1/GLP-1R/cAMP/PKA/CREB/INS pathway.

Gut microbiota variances reflecting the severity type 2 diabetes mellitus (T2DM). Achyranthes bidentata polysaccharide (ABP) can regulate gut microbiota. However, the hypoglycemic effect and underlying mechanism of ABP remain unclear. Herein, we characterized the structure of ABP and revealed the hypoglycemic effect of ABP in mice with T2DM. ABP repaired the intestinal barrier in T2DM mice and regulated the composition and abundance of gut microbiota, especially increasing bacteria which producing short-chain fatty acids (SCFAs), then increasing glucagon-like peptide-1 (GLP-1) level. The abundance of these bacteria was positively correlated with blood lipid and INS levels, negatively correlated with FBG levels. Colon transcriptome data and immunohistochemistry demonstrated that the alleviating T2DM effect of ABP was related to activation of the GLP-1/GLP-1 receptor (GLP-1R)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-response element binding protein (CREB)/INS pathway. Fecal microbiota transplantation (FMT) confirmed the transmissible efficacy of ABPs through gut microbiota. Overall, our research shows that ABP plays a hypoglycemic role by increasing gut microbiota-derived SCFAs levels, and activating the GLP-1/GLP-1R/cAMP/PKA/CREB/INS pathway, emphasizing ABP as promising T2DM therapeutic candidates.

Stocking and supplying naloxone: Findings from a representative sample of community pharmacies in Victoria, Australia.

INTRODUCTION: Naloxone is an opioid receptor antagonist, which can rapidly reverse the effects of an opioid overdose. Community pharmacists may experience several barriers to stocking and supplying naloxone including a lack of confidence or knowledge and time constraints. The current study aimed to examine the extent to which Victorian community pharmacies stock and supply naloxone and determine specific characteristics associated with stocking naloxone. METHODS: A representative sample of community pharmacists (n = 558) in Victoria, Australia, were contacted between October and November 2020 and invited to participate in an online survey. Data related to pharmacy- and pharmacist-related characteristics, including stocking and frequency of supplying naloxone in the past year. Multivariate logistic regression analysis was performed to examine the effect of various covariates on stocking naloxone. RESULTS: The sample comprised 265 pharmacists (response rate 47%). Most pharmacies were located in Melbourne (the capital city of Victoria, 59.6%) and were part of a pharmacy chain (61.5%). In total, 100 (38%) pharmacies stocked naloxone, a third of whom did not supply it in the past year. Pharmacies that provided opioid agonist treatment had 2.4 times higher odds of stocking naloxone (95% confidence interval 1.425-4.136; p = 0.001). DISCUSSION AND CONCLUSION: Less than half of Victorian community pharmacies stock naloxone, with even fewer actually supplying it in the past year. Future efforts are needed to increase the number of pharmacies that stock naloxone and the frequency in which it is supplied, while also addressing possible barriers to stocking and supplying naloxone among community pharmacists.

Trends in breast cancer mortality attributable to metabolic risks in Chinese women from 1990 to 2019: an age-period-cohort analysis.

Objective: Metabolic risks (MRs) are the primary determinants of breast cancer (BC) mortality among women. This study aimed to examine the changing trends in BC mortality associated with MRs and explore how they related to age, time period, and birth cohorts in Chinese women aged 25 and above. Methods: Data were sourced from the Global Burden of Disease Study 2019 (GBD2019). The BC mortality trajectories and patterns attributable to MRs were assessed using Joinpoint regression. The age-period-cohort (APC) model was employed to evaluate cohort and time period effects. Results: The age-standardized mortality rate (ASMR) of BC mortality linked to MRs displayed an escalating trend from 1990 to 2019, demonstrating an average annual percentage change (AAPC) of 1.79% (95% CI: 1.69~1.87). AAPCs attributable to high fasting plasma glucose (HFPG) and high body mass index (HBMI) were 0.41% (95% CI: 0.32~0.53) and 2.75% (95% CI: 2.68~2.82), respectively. APC analysis revealed that BC mortality due to HBMI in women aged 50 and above showed a rise with age and mortality associated with HFPG consistently demonstrated a positive correlation with age. The impact of HBMI on BC mortality significantly outweighed that of HFPG. The risk of BC mortality linked to HBMI has steadily increased since 2005, while HFPG demonstrated a trend of initial increase followed by a decrease in the period effect. Regarding the cohort effect, the relative risk of mortality was greater in the birth cohort of women after the 1960s of MRs on BC mortality, whereas those born after 1980 displayed a slight decline in the relative risk (RR) associated with BC mortality due to HBMI. Conclusion: This study suggests that middle-aged and elderly women should be considered as a priority population, and control of HBMI and HFPG should be used as a primary tool to control metabolic risk factors and effectively reduce BC mortality.

ROS-Induced Gingival Fibroblast Senescence: Implications in Exacerbating Inflammatory Responses in Periodontal Disease.

Periodontal disease is the pathological outcome of the overwhelming inflammation in periodontal tissue. Cellular senescence has been associated with chronic inflammation in several diseases. However, the role of cellular senescence in the pathogenesis of periodontal disease remained unclear. This study aimed to investigate the role and the mechanism of cellular senescence in periodontal disease. Using single-cell RNA sequencing, we first found the upregulated level of cellular senescence in fibroblasts and endothelial cells from inflamed gingival tissue. Subsequently, human gingival fibroblasts isolated from healthy and inflamed gingival tissues were labeled as H-GFs and I-GFs, respectively. Compared to H-GFs, I-GFs exhibited a distinct cellular senescence phenotype, including an increased proportion of senescence-associated ß-galactosidase (SA-ß-gal) positive cells, enlarged cell morphology, and significant upregulation of p16INK4A expression. We further observed increased cellular reactive oxygen species (ROS) activity, mitochondrial ROS, and DNA damage of I-GFs. These phenotypes could be reversed by ROS scavenger NAC, which suggested the cause of cellular senescence in I-GFs. The migration and proliferation assay showed the decreased activity of I-GFs while the gene expression of senescence-associated secretory phenotype (SASP) factors such as IL-1ß, IL-6, TGF-ß, and IL-8 was all significantly increased. Finally, we found that supernatants of I-GF culture induced more neutrophil extracellular trap (NET) formation and drove macrophage polarization toward the CD86-positive M1 pro-inflammatory phenotype. Altogether, our findings implicate that, in the inflamed gingiva, human gingival fibroblasts acquire a senescent phenotype due to oxidative stress-induced DNA and mitochondrial damage, which in turn activate neutrophils and macrophages through the secretion of SASP factors.

Capture, Coding, and Reporting of Health Care and Medicine Information in Australian Workers' Compensation Systems.

OBJECTIVE: This study aims to characterize the approaches to collecting, coding, and reporting health care and medicines data within Australian workers' compensation schemes. METHODS: We conducted a cross-sectional survey of data and information professionals in major Australian workers' compensation jurisdictions. Questionnaires were developed with input from key informants and a review of existing documentation. RESULTS: Twenty-five participants representing regulators (40%) and insurers (60%) with representation from all Australian jurisdictions were included. Health care and medicines data sources, depth, coding standards, and reporting practices exhibited significant variability across the Australian workers' compensation schemes. CONCLUSIONS: Substantial variability exists in the capture, coding, and reporting of health care and medicine data in Australian workers' compensation jurisdictions. There are opportunities to advance understanding of medicines and health service delivery in these schemes through greater harmonization of data collection, data coding, and reporting.

The Critical Role of Pyroptosis in Peri-Implantitis.

Background: Peri-implantitis (PI) is a prevalent complication of implant treatment. Pyroptosis, a distinctive inflammatory programmed cell death, is crucial to the pathophysiology of PI. Despite its importance, the pyroptosis-related genes (PRGs) influencing PI's progression remain largely unexplored. Methods: This study conducted histological staining and transcriptome analyze from three datasets. The intersection of differentially expressed genes (DEGs) and PRGs was identified as pyroptosis-related differentially expressed genes (PRDEGs). Functional enrichment analyses were conducted to shed light on potential underlying mechanisms. Weighted Gene Co-expression Network Analysis (WGCNA) and a pyroptotic macrophage model were utilized to identify and validate hub PRDEGs. Immune cell infiltration in PI and its relationship with hub PRDEGs were also examined. Furthermore, consensus clustering was performed to identify new PI subtypes. Protein-protein interaction (PPI) network, competing endogenous RNA (ceRNA) network, mRNA-mRNA binding protein regulatory (RBP) network, and mRNA-drugs regulatory network of hub PRDEGs were also analyzed. Results: Eight hub PRDEGs were identified: PGF, DPEP1, IL36B, IFIH1, TCEA3, RIPK3, NET7, and TLR3, which are instrumental in the PI's progression. Two PI subtypes were distinguished, with Cluster 1 exhibiting higher immune cell activation. The exploration of regulatory networks provided novel mechanisms and therapeutic targets in PI. Conclusion: Our research highlights the critical role of pyroptosis and identifies eight hub PRDEGs in PI's progression, offering insights into novel immunotherapy targets and laying the foundation for advanced diagnostic and treatment strategies. This contributes to our understanding of PI and underscores the potential for personalized clinical management.

Comparison of the osteogenic potential of fibroblasts from different sources.

OBJECTIVE: With the growing interest in the role of fibroblasts in osteogenesis, this study presents a comparative evaluation of the osteogenic potential of fibroblasts derived from three distinct sources: human gingival fibroblasts (HGFs), mouse embryonic fibroblasts (NIH3T3 cells), and mouse subcutaneous fibroblasts (L929 cells). MC3T3-E1 pre-osteoblast cells were employed as a positive control for osteogenic behavior. DESIGN: Our assessment involved multiple approaches, including vimentin staining for cell origin verification, as well as ALP and ARS staining in conjunction with RT-PCR for osteogenic characterization. RESULTS: Our findings revealed the superior osteogenic differentiation capacity of HGFs compared to MC3T3-E1 and NIH3T3 cells. Analysis of ALP staining confirmed that early osteogenic differentiation was most prominent in MC3T3-E1 cells at 7 days, followed by NIH3T3 and HGFs. However, ARS staining at 21 days demonstrated that HGFs produced the highest number of calcified nodules, indicating their robust potential for late-stage mineralization. This late-stage osteogenic potential of HGFs was further validated through RT-PCR analysis. In contrast, L929 cells displayed no significant osteogenic differentiation potential. CONCLUSIONS: In light of these findings, HGFs emerge as the preferred choice for seed cells in bone tissue engineering applications. This study provides valuable insights into the potential utility of HGFs in the fields of bone tissue engineering and regenerative medicine.

A randomized trial of Bacteroides fragilis 839 on preventing chemotherapy-induced myelosuppression and gastrointestinal adverse effects in breast cancer patients.

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.

Melanoidin-like carbohydrate-containing macromolecules from Shanxi aged vinegar exert immunoenhancing effects on macrophage RAW264.7 cells.

Bioactive macromolecule mining is important for the functional chemome analysis of traditional Chinese vinegar. In this study, we isolated and characterized carbohydrate-containing macromolecules from Shanxi aged vinegar (CCMSAV) and evaluated their immunomodulatory activity. The isolation process involved ethanol precipitation, deproteinization, decolorization, and DEAE-650 M column chromatography, resulting in the acquisition of four sub-fractions. All sub-fractions exhibited a molecular weight range of 6.92 to 16.71 kDa and were composed of 10 types of monosaccharides. Comparative analysis of these sub-fractions with two melanoidins exhibited similarities in elemental composition, spectral signature, and pyrolytic characteristics. Immunological assays confirmed the significantly enhanced cell viability, phagocytic activity, and secretion of nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-6 in RAW264.7 cells by all four sub-fractions. Further investigation of the immunomodulatory mechanism revealed that SAV-RP70-X, the most potent purified sub-fraction, enhanced aerobic glycolysis in macrophages and activated Toll-like receptor 2 (TLR2), TLR4, mannose receptor (MR), scavenger receptor (SR), and the dendritic cell-associated C-type lectin-1 receptor (Dectin-1). Furthermore, the activation of macrophages was associated with the MyD88/PI3K/Akt/NF-κB signaling pathway. Methylation analysis revealed that 1,4-Xylp was the most abundant glycosidic linkage in SAV-RP70-X.

Microbes translocation from oral cavity to nasopharyngeal carcinoma in patients.

The presence of oral microbes in extra-oral sites is linked to gastrointestinal cancers. However, their potential ectopically colonization in the nasopharynx and impact on local cancer development remains uncertain. Our study involving paired nasopharyngeal-oral microbial samples from nasopharyngeal carcinoma (NPC) patients and controls unveils an aberrant oral-to-nasopharyngeal microbial translocation associated with increased NPC risk (OR = 4.51, P = 0.012). Thirteen species are classified as oral-translocated and enriched in NPC patients. Among these, Fusobacterium nucleatum and Prevotella intermedia are validated through culturomics and clonal strain identification. Nasopharyngeal biopsy meta-transcriptomes confirm these microbes within tumors, influencing local microenvironment and cytokine response. These microbes correlate significantly with the Epstein-Barr virus (EBV) loads in the nasopharynx, exhibiting an increased dose-response relationship. Collectively, our study identifies oral microbes migrating to the nasopharynx, infiltrating tumors, impacting microenvironments and linking with EBV infection. These results enhance our understanding of abnormal microbial communication and their roles in carcinogenesis.

S-nitrosoglutathione reductase-dependent p65 denitrosation promotes osteoclastogenesis by facilitating recruitment of p65 to NFATc1 promoter.

Osteoclasts, the exclusive bone resorptive cells, are indispensable for bone remodeling. Hence, understanding novel signaling modulators regulating osteoclastogenesis is clinically important. Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) is a master transcription factor in osteoclastogenesis, and binding of NF-κB p65 subunit to NFATc1 promoter is required for its expression. It is well-established that DNA binding activity of p65 can be regulated by various post-translational modifications, including S-nitrosation. Recent studies have demonstrated that S-nitrosoglutathione reductase (GSNOR)-mediated protein denitrosation participated in cell fate commitment by regulating gene transcription. However, the role of GSNOR in osteoclastogenesis remains unexplored and enigmatic. Here, we investigated the effect of GSNOR-mediated denitrosation of p65 on osteoclastogenesis. Our results revealed that GSNOR was up-regulated during osteoclastogenesis in vitro. Moreover, GSNOR inhibition with a chemical inhibitor impaired osteoclast differentiation, podosome belt formation, and bone resorption activity. Furthermore, GSNOR inhibition enhanced the S-nitrosation level of p65, precluded the binding of p65 to NFATc1 promoter, and suppressed NFATc1 expression. In addition, mouse model of lipopolysaccharides (LPS)-induced calvarial osteolysis was employed to evaluate the therapeutic effect of GSNOR inhibitor in vivo. Our results indicated that GSNOR inhibitor treatment alleviated the inflammatory bone loss by impairing osteoclast formation in mice. Taken together, these data have shown that GSNOR activity is required for osteoclastogenesis by facilitating binding of p65 to NFATc1 promoter via promoting p65 denitrosation, suggesting that GSNOR may be a potential therapeutic target in the treatment of osteolytic diseases.

Janus silk fibroin/polycaprolactone-based scaffold with directionally aligned fibers and porous structure for bone regeneration.

To promote bone repair, it is desirable to develop three-dimensional multifunctional fiber scaffolds. The densely stacked and tightly arranged conventional two-dimensional electrospun fibers hinder cell penetration into the scaffold. Most of the existing three-dimensional structural materials are isotropic and monofunctional. In this research, a Janus nanofibrous scaffold based on silk fibroin/polycaprolactone (SF/PCL) was fabricated. SF-encapsulated SeNPs demonstrated stability and resistance to aggregation. The outside layer (SF/PCL/Se) of the Janus nanofiber scaffold displayed a structured arrangement of fibers, facilitating cell growth guidance and impeding cell invasion. The inside layer (SF/PCL/HA) featured a porous structure fostering cell adhesion. The Janus fiber scaffold containing SeNPs notably suppressed S. aureus and E. coli activities, correlating with SeNPs concentration. In vitro, findings indicated considerable enhancement in alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts and upregulation of genes linked to osteogenic differentiation with exposure to the SF/PCL/HA/Se Janus nanofibrous scaffold. Moreover, in vivo, experiments demonstrated successful critical bone defect repair in mouse skulls using the SF/PCL/HA/Se Janus nanofiber scaffold. These findings highlight the potential of the SF/PCL-based Janus nanofibrous scaffold, integrating SeNPs and nHA, as a promising biomaterial in bone tissue engineering.

Association of state-level prescription drug monitoring program implementation with opioid prescribing transitions in primary care in Australia.

AIMS: This study aimed to evaluate whether voluntary and mandatory prescription drug monitoring program (PDMP) use in Victoria, Australia, had an impact on prescribing behaviour, focusing on individual patients' prescribed opioid doses and transition to prescribing of nonmonitored medications. METHODS: This was a retrospective cross-sectional study using routinely collected primary healthcare data. A 90-day moving average prescribed opioid dose in oral morphine equivalents was used to estimate opioid dosage. A Markov transition matrix was used to describe how patients prescribed medications transitioned between opioid dose groups and other nonopioid treatment options during 3 transition periods: transition between 2 control periods prior to PDMP implementation (T1 to T2); during the voluntary PDMP implementation (T2 to T3); and during mandatory PDMP implementation (T3 to T4). RESULTS: Among patients prescribed opioids in our study, we noted an increased probability of transitioning to not being prescribed opioids during the mandatory PDMP period (T3 to T4). This increase was attributed mainly to the ceasing of low-dose opioid prescribing. Membership in an opioid dose group remained relatively stable for most patients who were prescribed high opioid doses. For those who were only prescribed nonmonitored medications initially, the probability of being prescribed opioids increased during the mandatory PDMP when compared to other transition periods. CONCLUSION: The introduction of PDMP mandates appeared to have an impact on the prescribing for patients who were prescribed low-dose opioids, while its impact on individuals prescribed higher opioid doses was comparatively limited.

Targeting type H vessels in bone-related diseases.

Blood vessels are essential for bone development and metabolism. Type H vessels in bone, named after their high expression of CD31 and Endomucin (Emcn), have recently been reported to locate mainly in the metaphysis, exhibit different molecular properties and couple osteogenesis and angiogenesis. A strong correlation between type H vessels and bone metabolism is now well-recognized. The crosstalk between type H vessels and osteoprogenitor cells is also involved in bone metabolism-related diseases such as osteoporosis, osteoarthritis, fracture healing and bone defects. Targeting the type H vessel formation may become a new approach for managing a variety of bone diseases. This review highlighted the roles of type H vessels in bone-related diseases and summarized the research attempts to develop targeted intervention, which will help us gain a better understanding of their potential value in clinical application.

Trajectories of prescription opioid tapering in patients with chronic non-cancer pain: a retrospective cohort study, 2015-2020.

OBJECTIVE: To identify common opioid tapering trajectories among patients commencing opioid taper from long-term opioid therapy for chronic non-cancer pain and to examine patient-level characteristics associated with these different trajectories. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: Patients prescribed opioid analgesics between 2015 and 2020. METHODS: Group-based trajectory modeling and multinomial logistic regression analysis were conducted to determine tapering trajectories and to examine demographic and clinical factors associated with the different trajectories. RESULTS: A total of 3369 patients commenced a taper from long-term opioid therapy. Six distinct opioid tapering trajectories were identified: low dose / completed taper (12.9%), medium dose / faster taper (12.2%), medium dose / gradual taper (6.5%), low dose / noncompleted taper (21.3%), medium dose / noncompleted taper (30.4%), and high dose / noncompleted taper (16.7%). A completed tapering trajectory from a high opioid dose was not identified. Among patients prescribed medium opioid doses, those who completed their taper were more likely to have higher geographically derived socioeconomic status (relative risk ratio [RRR], 1.067; 95% confidence interval [CI], 1.001-1.137) and less likely to have sleep disorders (RRR, 0.661; 95% CI, 0.463-0.945) than were those who didn't complete their taper. Patients who didn't complete their taper were more likely to be prescribed strong opioids (eg, morphine, oxycodone), regardless of whether they were tapered from low (RRR, 1.444; 95% CI, 1.138-1.831) or high (RRR, 1.344; 95% CI, 1.027-1.760) doses. CONCLUSIONS: Those prescribed strong opioids and high doses appear to be less likely to complete tapering. Further studies are needed to evaluate the clinical outcomes associated with the identified trajectories.

Biphasic calcium phosphate recruits Tregs to promote bone regeneration.

The use of bone substitute materials is crucial for the healing of large bone defects. Immune response induced by bone substitute materials is essential in bone regeneration. Prior research has mainly concentrated on innate immune cells, such as macrophages. Existing research suggests that T lymphocytes, as adaptive immune cells, play an indispensable role in bone regeneration. However, the mechanisms governing T cell recruitment and specific subsets that are essential for bone regeneration remain unclear. This study demonstrates that CD4+ T cells are indispensable for ectopic osteogenesis by biphasic calcium phosphate (BCP). Subsequently, the recruitment of CD4+ T cells is closely associated with the activation of calcium channels in macrophages by BCP to release chemokines Ccl3 and Ccl17. Finally, these recruited CD4+ T cells are predominantly Tregs, which play a significant role in ectopic osteogenesis by BCP. These findings not only shed light on the immune-regenerative process after bone substitute material implantation but also establish a theoretical basis for developing bone substitute materials for promoting bone tissue regeneration. STATEMENT OF SIGNIFICANCE: Bone substitute material implantation is essential in the healing of large bone defects. Existing research suggests that T lymphocytes are instrumental in bone regeneration. However, the specific mechanisms governing T cell recruitment and specific subsets that are essential for bone regeneration remain unclear. In this study, we demonstrate that activation of calcium channels in macrophages by biphasic calcium phosphate (BCP) causes them to release the chemokines Ccl3 and Ccl17 to recruit CD4+ T cells, predominantly Tregs, which play a crucial role in ectopic osteogenesis by BCP. Our findings provide a theoretical foundation for developing bone substitute material for bone tissue regeneration.

Beneficial effect of vinegar consumption associated with regulating gut microbiome and metabolome.

Vinegar is used as fermented condiment and functional food worldwide. Vinegar contains many nutrients and bioactive components, which exhibits health benefits. In this study, the potential effects of Shanxi aged vinegar (SAV) on gut microbiome and metabolome were explored in normal mice. The levels of inflammatory factors were significantly decreased in SAV-treated mice. Immunoglobulin, NK cells and CD20 expression were significantly increased after SAV administration. In addition, SAV intake altered gut microbiota structure by up-regulating Verrucomicrobia, Akkermansia, Hungatella and Alistipes, and down-regulating Firmicutes, Lachnospiraceae_NK4A136_group and Oscillibacter. The differential metabolites were mainly included amino acids, carbohydrates and bile acids. Furthermore, after SAV intake, Verrucomicrobia, and Akkermansia closely impacted the related gut metabolites. These alterations of gut microbiota-related metabolism further modulated some immunoregulatory and inflammatory factors, and confer potential health benefits. Our results imply that vinegar consumption has beneficial effects on regulating gut microbiome and metabolome.

Risk assessment and source identification of soil heavy metals: a case study of farmland soil along a river in the southeast of a mining area in Southwest China.

To investigate the heavy metals (HMs) contamination of surface farmland soil along the river in the southeast of a mining area in southwest China and identify the contamination sources, 54 topsoil samples were collected and the concentrations of seven elements (Zn, Ni, Pb, Cu, Hg, Cr, and Co) were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic fluorescence spectrometry (AFS). The geo-accumulation index ([Formula: see text]) and comprehensive potential ecological risk index ([Formula: see text]) were used for analysis to determine the pollution degree of HMs and the risk level of the study area. Meanwhile, the Positive Matrix Factorization (PMF) model was combined with a variety of statistical methods to determine the sources of HMs. To explore the influence of the river flowing through the mining area on the concentrations of HMs in the farmland soil, 15 water samples were collected and the concentrations of the above seven elements were determined. The results showed that the concentrations of Pb, Cu, and Zn in soil all exceeded the risk screening value, and Pb in soil of some sampling sites exceeded control value of "Agricultural Land Soil Pollution Risk Control Standard".[Formula: see text] showed that Pb was heavily contaminated, while Cu and Zn were moderately contaminated. RI showed that the study area was at moderate risk. PMF and various statistical methods showed that the main source of HMs was the industrial source. In the short term, the river flowing through the mine has no significant influence on the concentration of HMs in the soil. The results provide a reference for the local government to control contamination and identify the sources of HMs.

A comprehensive predictive model for radiation-induced brain injury in risk stratification and personalized radiotherapy of nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Radiation-induced brain injury (RBI) is a severe radiotoxicity for nasopharyngeal carcinoma (NPC) patients, greatly affecting their long-term life quality and survival. We aim to establish a comprehensive predictive model including clinical factors and newly developed genetic variants to improve the precision of RBI risk stratification. MATERIALS AND METHODS: By performing a large registry-based retrospective study with magnetic resonance imaging follow-up on RBI development, we conducted a genome-wide association study and developed a polygenic risk score (PRS) for RBI in 1189 NPC patients who underwent intensity-modulated radiotherapy. We proposed a tolerance dose scheme for temporal lobe radiation based on the risk predicted by PRS. Additionally, we established a nomogram by combining PRS and clinical factors for RBI risk prediction. RESULTS: The 38-SNP PRS could effectively identify high-risk individuals of RBI (P = 1.42 × 10-34). Based on genetic risk calculation, the recommended tolerance doses of temporal lobes should be 57.6 Gy for individuals in the top 10 % PRS subgroup and 68.1 Gy for individuals in the bottom 50 % PRS. Notably, individuals with high genetic risk (PRS > P50) and receiving high radiation dose in the temporal lobes (D0.5CC > 65 Gy) had an approximate 50-fold risk over individuals with low PRS and receiving low radiation dose (HR = 50.09, 95 %CI = 24.27-103.35), showing an additive joint effect (Pinteraction < 0.001). By combining PRS with clinical factors including age, tumor stage, and radiation dose of temporal lobes, the predictive accuracy was significantly improved with C-index increased from 0.78 to 0.85 (P = 1.63 × 10-2). CONCLUSIONS: The PRS, together with clinical factors, could improve RBI risk stratification and implies personalized radiotherapy.

Opioid characteristics and nonopioid interventions associated with successful opioid taper in patients with chronic noncancer pain.

ABSTRACT: Current research indicates that tapering opioids may improve pain and function in patients with chronic noncancer pain. However, gaps in the literature remain regarding the choice of opioid and nonopioid interventions to support a successful taper. This study used an Australian primary care data set to identify a cohort of patients on long-term opioid therapy commencing opioid taper between January 2016 and September 2019. Using logistic regression analysis, we compared key clinical factors associated with differing taper outcomes. Of a total of 3371 patients who commenced taper, 1068 (31.7%) completed taper within 12 months. In the 3 months after commencement of taper, compared with those who did not complete taper, patients who successfully completed opioid taper were less likely to be prescribed buprenorphine (odds ratio [OR] 0.691; 95% CI: 0.530-0.901), fentanyl (OR, 0.429; 95% CI: 0.295-0.622), and long-acting (LA) opioids, including methadone (OR, 0.349; 95% CI: 0.157-0.774), oxycodone-naloxone (OR, 0.521; 95% CI: 0.407-0.669), and LA tapentadol (OR, 0.645; 95% CI: 0.461-0.902), but more likely to be prescribed codeine (OR, 1.308; 95% CI: 1.036-1.652). Compared with those who did not complete taper, patients who successfully tapered were less likely to be prescribed any formulations of oxycodone (short-acting [SA]: OR, 0.533; 95% CI: 0.422-0.672, LA: OR, 0.356; 95% CI: 0.240-0.530) and tramadol (SA: OR, 0.370; 95% CI: 0.218-0.628, LA: OR, 0.317; 95% CI: 0.234-0.428). The type of opioid prescribed in the months after commencement of taper seems to influence the taper outcomes. These findings may inform prospective studies on opioid taper.