Deep hydrocarbon genesis and accumulation model of strike-slip fault reservoirs in the Yuemanxi area of the Tarim Basin.

As a clean and environmentally friendly energy source, deep oil and gas has always been the focus of the oil and gas industry. The study of hydrocarbon accumulation in deep strike-slip fault zones is a challenging and important area of research in the oil and gas industry. In particular, accurately modeling oil and gas accumulation in the Yuemenxi area of the Tarim Basin presents significant difficulties due to the varying physical properties and gas composition of the Ordovician reservoirs, as well as the complex origin of oil and gas in the area. However, by calculating biomarker parameter maturity on oil samples from strike-slip faults, researchers have discovered that the light oil in the area is sourced from high maturity source rocks in the Later Caledonian, with vitrinite reflectance ranging from 0.79% to 1.11%. The complete distribution of n-alkanes and high concentration of low-carbon n-alkanes in the crude oil suggest that the fluid in the reservoir has not undergone any secondary alteration since its initial accumulation. The carbon isotope and component ratio analysis of natural gas in the Yuemanxi area indicates that the Ordovician natural gas is predominantly kerogen cracking gas. Comprehensive hydrocarbon genesis and accumulation conditions, this paper presents a differential accumulation model for the Ordovician reservoirs in the region, which were controlled by strike-slip faults and source rocks. Based on these findings, it can be inferred that there is significant potential for oil and gas exploration and development in the deeper layers of these strike-slip fault zones.

Immunomodulatory effects of umbilical mesenchymal stem cell-derived exosomes on CD4+ T cells in patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4+ T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4+ T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4+ T cells in pSS, and whether the effects via the autophagy pathway remains unclear. METHODS: The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4+ T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4+ T cells were determined using flow cytometry. Autophagosomes of CD4+ T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR. RESULTS: The study demonstrated that the peripheral blood CD4+ T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4+ T cells in pSS patients, blocked them in the G0/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-ß secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4+ T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4+ T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance in pSS patients through the autophagy pathway. CONCLUSIONS: The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4+ T cells, and maybe as a new treatment for pSS.

Hybrid Nanostructure Catalyst with Low Loading of Pt for the High-Efficiency Catalytic Hydrogenation of Chloronitrobenzene.

Fabrication of low-loading, noble-metal, stable, and high-performance metal catalysts remains a thorny issue. Herein, we demonstrate the successful formation of a hybrid nanostructure Pt/TiO2/SBA-15 catalyst (denoted as HNSC-P/T/S; Pt, 0.09%; TiO2, 10%) with satisfactory activity in the hydrogenation of para-chloronitrobenzene (p-CNB). The HNSC-P/T/S showed >99% conversion and a high selectivity of >98%, and the turnover frequency number (TOF) reached 66 766 h-1, which was impossible to achieve with Pt/TiO2 (denoted as P/T) or Pt/SBA-15 (denoted as P/S). The success of the catalytic activity of the HNSC-P/T/S mainly relies on its synergistic effect and special structure, which can fully develop the catalytic ability of Pt, thereby reducing the Pt loading in the noble-based catalyst. Furthermore, the HNSC-P/T/S could also achieve an excellent catalytic activity in the hydrogenation of other nitroarenes. Hence, this work proposes a direction to prepare a noble-based catalyst with a low loading of noble metals for diverse applications.

Fluorinated leaning pillar[6]arene: synthesis, structure and selective iodide anion binding by anion-π interactions.

Anion recognition has continuously attracted significant attention due to its important role in environmental and biological sciences. Here, we have designed and synthesized an electron-deficient fluorinated leaning pillar[6]arene 1 that contains two tetrafluoro-benzene units. The electron-deficient fluorinated leaning pillar[6]arene 1 is capable of selectively recognizing iodide anions to form a host-guest complex with 1 : 1 stoichiometry driven by anion-π interactions. Our work ascribes this selective recognition to the preorganization of macrocycles, suitable cavity size, and the effect of anion-π interactions. The innovative application of this macrocycle offers us a new avenue for the design of selective receptors for anions and electron-deficient macrocyclic arenes.

Prevalence of myopia and associated risk factors among key schools in Xi'an, China.

BACKGROUND: The aim of this study is to investigate the prevalence of myopia and high myopia and the associated risk factors in key schools in Xi'an, China. METHODS: This cross-sectional study started in September 2021 and was conducted for one month. A total of 11,011 students from 10 key primary schools, five key junior high schools and five key high schools in Xi'an were randomly selected to undergo visual acuity measurement and non-cycloplegic autorefraction. The questionnaire was completed by the students and their parents together. RESULTS: The prevalence of myopia and high myopia in key schools were 75.7% and 9.7%, respectively. The prevalence of myopia and high myopia rose significantly as grade or age increased (all P < 0.001), and the prevalence of myopia and high myopia in females was higher than that in males (P < 0.001, P < 0.5). According to the multivariable logistic regression analysis, older age (OR=1.42), female compared with male (OR=1.43), having one myopic parent (OR=1.64), having two myopic parent (OR=2.30) and often taking extracurricular tuition (OR=1.35) were more likely to be associated with develop myopia (P < 0.001). Older age (OR=1.39), having one myopic parent (OR=2.29), having two myopic parent (OR= 3.69), and often taking extracurricular tuition (OR=1.48) were more likely to be associated with high myopia (P < 0.001). CONCLUSIONS: The overall rate of myopia and high myopia in key schools in Xi'an, China, is extremely high. Myopia and high myopia are associated with increasing age, parents' myopia, few outdoor exercises, and extracurricular tuition. Myopia is also associated with female and not having the habit of "one punch, one foot, one inch (when reading and writing, 10 cm from the chest to the table, 33 cm from the eye to the book and 3.3 cm from the tip of the pen to the finger)".

Efficacy of scaling and root planning with periodontal endoscopy for residual pockets in the treatment of chronic periodontitis: a randomized controlled clinical trial.

OBJECTIVES: Residual pockets are a risk factor of periodontitis progression. This study evaluated the efficacy of periodontal endoscopy (PE) during scaling and root planning (SRP) of residual pockets in chronic periodontitis patients after initial periodontal treatment. MATERIALS AND METHODS: A single-blinded, randomized controlled clinical trial was conducted in systemically healthy subjects presenting at least three residual pockets with a probing depth (PD) ≥ 5 mm in each quadrant. Subjects were randomly allocated to one of two trial groups using a computer-generated program: SRP + PE (test group) or SRP alone (control group). Clinical parameters (PD, clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PLI)) were then measured at baseline, 3-, and 6-month follow-up. RESULTS: A total of 1629 sites in 37 patients were examined. Both treatments significantly improved all clinical outcomes (PD, CAL, BOP, and PLI) from baseline to 6 months (P < 0.05), although greater reductions in PD and PLI were observed in the test group at both 3- (PD: 3.45 ± 0.56 vs. 4.14 ± 0.59 mm; PLI: 0.55 ± 0.23 vs. 0.73 ± 0.27) and 6-month follow-up (PD: 3.12 ± 0.63 vs. 4.0 ± 0.68 mm; PLI: 0.49 ± 0.21 vs. 0.72 ± 0.28, respectively; P = 0.001 for PD and P = 0.021 for PLI). No significant differences in CAL or BOP were observed. CONCLUSIONS: SRP + PE resulted in significant reductions in PD and PLI compared to SRP alone in residual pockets with a PD ≥ 5 mm. CLINICAL RELEVANCE: The findings highlight the benefits of SRP + PE, supporting use as an alternative strategy in nonsurgical periodontal treatment.

Diminished CD68+ Cancer-Associated Fibroblast Subset Induces Regulatory T-Cell (Treg) Infiltration and Predicts Poor Prognosis of Oral Squamous Cell Carcinoma Patients.

Although cancer-associated fibroblasts (CAFs) are crucial stromal cells, characterizing their heterogeneity is far from complete. This study reports a novel subset of CAFs in oral squamous cell carcinoma (OSCC), which positively expressed CD68, the classic marker of macrophages. The spatial and temporal distribution of the CD68+ CAF subset of OSCC (n = 104) was determined by CD68/actin alpha 2, smooth muscle (ACTA2+; α-SMA) immunohistochemistry of serial sections. The CD68+ α-SMA+ CAF subset was elevated from dysplasia to OSCC. Moreover, although both the tumor center and invasive front harbor an abundant CD68+ CAF subset, patients with low-CD68+ CAFs in the tumor center showed more recurrence after operation and shorter survival time, indicating the different function of CD68+ CAFs in tumor initiation and progression. Functional analysis in the OSCC-CAF co-culture system found knockdown of CD68 did not change the phenotype of CAFs, tumor growth, or migration. Unexpectedly, low-CD68+ CAFs were associated with aberrant immune balance. A high proportion of tumor-supportive Tregs was found in patients with low-CD68+ CAFs. Mechanistically, knockdown of CD68 in CAFs contributed to the up-regulation of chemokine CCL17 and CCL22 of tumor cells to enhance Treg recruitment. Thus, up-regulated CD68+ fibroblasts participate in tumor initiation, but the low-CD68+ CAF subset in OSCC is conducive to regulatory T-cell (Treg) recruitment in the tumor microenvironment and contribute to poor prognosis of OSCC patients.

The potential value of plasma receptor interacting protein 3 in neonates with culture-positive late-onset sepsis.

BACKGROUND: Late-onset sepsis (LOS) is a systemic inflammatory response syndrome in neonates, and the molecular mechanism of LOS is incompletely characterized. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in LOS. METHODS: 63 neonates with LOS supported by positive culture and 79 neonates without sepsis were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with the whole blood hypersensitive C-reactive protein (hs-CRP) level and platelet count (PLT). Differences in RIP3, hs-CRP and PLT between the two groups were compared. Changes in the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for LOS was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In the sepsis group, RIP3 and hs-CRP levels were significantly higher than those in the control group (RIP3, p < 0.0001; hs-CRP, p < 0.0001), and PLT was significantly lower than that in the control group (p < 0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors were significantly decreased (p < 0.0001) and PLT significantly improved (p = 0.0216). With RIP3 > 15,845.19 pg/mL, hs-CRP > 5.00 mg/L, and PLT < 204.00 × 109/L as the positive criteria, the sensitivity values of the three indicators in the diagnosis of LOS were 69.8%, 60.3%, 60.3%, respectively, and the specificity values were 92.4%, 96.2%, 79.8%, respectively. The combination of RIP3, hs-CRP and PLT had a sensitivity of 77.8% and specificity of 97.5%. CONCLUSIONS: RIP3 may contribute to the early diagnosis of LOS and monitoring of treatment effect. The combined detection of RIP3, hs-CRP and PLT may be more effective than individual detection in the diagnosis of LOS.

An inexpensive anaerobic chamber for the genetic manipulation of strictly anaerobic bacteria.

Strictly anaerobic bacteria are important to both human health and industrial usage. These bacteria are sensitive to oxygen, therefore, it is preferable to manipulate these microbes in an anaerobic chamber. However, commercial anaerobic chambers (CACs) are expensive, making them less accessible to scientists with a limited budget, especially to those in developing countries. The high price of commercial chambers has hindered, at least partially, the progress of research on anaerobes in developing countries. In the research presented here, we developed an inexpensive and reliable anaerobic chamber and successfully achieved routine maintenance of eleven strictly anaerobic bacterial strains. Furthermore, genetic manipulation examples have been set for both Clostridioidesdifficile 630 and Clostridiumbeijerinckii NCIMB 8052 strains to validate that the chamber could applied to advanced genetic engineering of strictly anaerobes. C. difficile and C. beijerinckii were both genetically manipulated in this chamber, showing it's utility for the genetic engineering of anaerobes. Most importantly, the anaerobic chamber was 76% - 88% less expensive than a CACs and has similar functionality with regards to the cultivation and manipulation of strictly anaerobic bacteria. The anaerobic chamber described in this study will promote the research of anaerobes in developing counties and scientists who have limited research budgets.

Significance of sTREM-1 in early prediction of ventilator-associated pneumonia in neonates: a single-center, prospective, observational study.

BACKGROUND: To evaluate whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) can be used as an early predictor of ventilator-associated pneumonia (VAP). METHODS: Ventilated neonatal patients admitted into the neonatology department between January 2017 and January 2018 were divided into VAP (n = 30) and non-VAP (n = 30) groups. Serum sTREM, procalcitonin (PCT), C-reactive protein and interleukin-6 levels were measured at 0, 24, 72, and 120 h after initiation of mechanical ventilation (MV). Correlations between blood biomarker concentrations and VAP occurrence were analyzed. Predictive factors for VAP were identified by logistic regression analysis and Hosmer-Lemeshow test, and the predictive value of sTREM-1 and biomarker combinations for VAP was determined by receiver operating characteristic curve analysis. RESULTS: The serum sTREM-1 concentration was significantly higher in the VAP group than in the non-VAP group after 72 and 120 h of MV (72 h: 289.5 (179.6-427.0) vs 202.9 (154.8-279.6) pg/ml, P < 0.001; 120 h: 183.9 (119.8-232.1) vs 141.3 (99.8-179.1) pg/ml, P = 0.042). The area under the curve (AUC) for sTREM-1 at 72 h was 0.902 with a sensitivity of 90% and specificity of 77% for the optimal cut-off value of 165.05 pg/ml. Addition of PCT to sTERM-1 at 72 h further improved the predictive value, with this combination having an AUC of 0.971 (95% confidence interval: 0.938-1.000), sensitivity of 0.96, specificity of 0.88, and Youden index of 0.84. CONCLUSION: sTREM-1 is a reliable predictor of VAP in neonates, and combined measurement of serum levels of sTREM-1 and PCT after 72 h of MV provided the most accurate prediction of VAP in neonatal patients.

Tumor-infiltrating lymphocyte-derived MLL2 independently predicts disease-free survival for patients with early-stage oral squamous cell carcinoma.

BACKGROUND: MLL2 (mixed-lineage leukemia 2) is recognized as an essential role in regulating histone 3 lysine 4 tri-methylation (H3K4me3) in mammalian cells. It is frequently mutated to promote developmental diseases and tumor initiation. However, the expression pattern of MLL2 and its clinical significance for patients with early-stage oral squamous cell carcinoma (OSCC) remain totally unknown. METHODS: Eighty-five samples of primary early-stage OSCC were enrolled in this retrospective study, and immunohistochemistry (IHC) was performed to detect the spatial pattern of MLL2. The diagnostic and prognostic value of MLL2 were assessed. RESULTS: MLL2 was widely expressed in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs), both in tumor center and invasive tumor front, and showed no distributive heterogeneity. Moreover, regardless of cell types and microlocalization, patients with high expressed MLL2 had increased depth invasion of tumor (DOI). Besides, upregulation of MLL2TC and MLL2TIL in tumor center were both associated with poor differentiation, but showed no correlation with tumor growth with comparable Ki-67 levels. Prognostic analysis indicated that early-stage OSCC patients with enhanced MLL2TIL in invasive tumor front were susceptible to occur postoperative metastasis and recurrence. Indeed, patients with higher expressed MLL2TIL showed shorter overall survival (OS) and disease-free survival (DFS), and MLL2TIL in invasive tumor front was an independent risk factor of DFS. CONCLUSION: TIL-derived MLL2 in invasive tumor front was an independent prognostic factor of DFS for early-stage OSCC patients.

Acute effects of the translocator protein drug ligand FGIN-1-27 on serum testosterone and luteinizing hormone levels in male Sprague-Dawley rats†.

We reported that FGIN-1-27 (N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide, FGIN), a synthetic ligand for translocator protein (TSPO, 18 kDa), increased serum testosterone levels in young and aged Brown Norway rats after its administration daily for 10 days. It is not known, however, how soon after treatment with FGIN serum testosterone rises, how long levels remain elevated after cessation of treatment, or whether the drug acts solely through TSPO. Adult Sprague-Dawley male rats received a single ip dose of FGIN (1 mg/kg BW). Serial blood samples were collected, and serum testosterone and luteinizing hormone (LH) were assessed hourly throughout 24 h. Testosterone concentration was maximal by 3 h, remained significantly higher than the controls at 10 h, and returned to the control level by 24 h. Consistent with the in vivo study, culturing isolated Leydig cells with either FGIN (40 µM) or LH (0.1 ng/ml) resulted in significantly increased testosterone production by 30 min, and the stimulatory effects persisted through 48 h. At a very early (15 min) treatment time, however, FGIN significantly increased testosterone production but LH had not yet done so. Surprisingly, in vivo treatment with FGIN not only increased serum testosterone but also serum LH concentration, raising the possibility that FGIN may increase serum testosterone concentration by dual mechanisms.

Tumor cell-derived TGF-ß at tumor center independently predicts recurrence and poor survival in oral squamous cell carcinoma.

BACKGROUND: Transforming growth factor-ß (TGF-ß) exerts its versatile function (oncogenic or tumor suppressive role) during the carcinogenesis in tumor microenvironment-dependent manner. Considering the tumor heterogeneity, spatial and temporal distribution of TGF-ß in oral squamous cell carcinoma (OSCC) remained to be elucidated. METHODS: Formalin-fixed, paraffin-embedded sections derived from 73 patients with OSCC were immunostained, revealing expression patterns of TGF-ß, both at the regions of tumor center (TC) and invasive tumor front (ITF). RESULTS: The TGF-ß levels on tumor cells, fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs) were comparable and showed to be cell-type-independent manner. Although TC regions harbored less positive staining of TGF-ß than ITF in tumor cells (TGF-ßTumor cell ) (89.0% vs 98.3%; P = 0.037), FLCs (TGF-ßFLC ) (86.3% vs 96.6%; P = 0.043), and TILs (TGF-ßTIL ) (83.6% vs 94.8%; P = 0.044), respectively, TGF-ß at TC regions, not at ITF, correlated to poor clinical outcomes. At TC regions, patients with high TGF-ßTumor cell had high recurrence rate, and patients with high TGF-ßTIL showed inferior worst pattern of invasion. Of note, high TGF-ßTumor cell at TC predicted shorter overall survival time, recurrence-free survival, and disease-free survival in patients with OSCC, whereas high TGF-ßTIL had no association with survival time. Cox regression analyses indicated that tumor cell-derived TGF-ß at TC was an independent risk factor for survival outcome in patients with OSCC. CONCLUSIONS: Tumor cell-derived TGF-ß at TC regions, but not at ITF, could be a promising predictor for disease recurrence and poor prognosis of patients with OSCC.

Antioxidant activity of phenylethanoid glycosides on glutamate-induced neurotoxicity.

Exposure of PC12 cells to 10 mM glutamate caused significant viability loss, cell apoptosis, decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as increased levels of malondialdehyde (MDA). In parallel, glutamate significantly increased the intracellular levels of ROS and intracellular calcium. However, pretreatment of the cells with acteoside and isoacteoside significantly suppressed glutamate-induced cellular events. Moreover, acteoside and isoacteoside reduced the glutamate-induced increase of caspase-3 activity and also ameliorated the glutamate-induced Bcl-2/Bax ratio reduction in PC12 cells. Furthermore, acteoside and isoacteoside significantly inhibited glutamate-induced DNA damage. In the mouse model, acteoside significantly attenuated cognitive deficits in the Y maze test and attenuated neuronal damage of the hippocampal CA1 regions induced by glutamate. These data indicated that acteoside and isoacteoside play neuroprotective effects through anti-oxidative stress, anti-apoptosis, and maintenance of steady intracellular calcium.

Comparative efficacy and tolerability of first-line treatments for untreated, HER2-negative, advanced gastric cancer: systematic review and network meta-analysis.

INTRODUCTION: This article provided direct comparisons across first-line regimens for patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer. We performed a network meta-analysis (NMA) of phase III trials to compare the efficacy and safety of first-line treatments for gastric cancer. METHODS: We conducted a systematic review and Bayesian or Frequentist network meta-analysis by searching relevant literature from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences from January 1, 2000 to May 1, 2023. This study was registered in the Prospective Register of Systematic Reviews (PROSPERO CRD42023414357) to ensure transparency. Randomized clinical trials (RCTs) that qualified the inclusion criteria were subjected to network meta-analysis and systematically reviewed. RESULTS: We included a total of 25 studies including 14389 patients and 23 first-line treatments. Overall, sintilimab plus capecitabine plus oxaliplatin (Sint-XELOX) appeared to confer the best overall survival (OS) (calculated using surface under the cumulative ranking curve [SUCRA], 81%), with significant differences versus fluorouracil plus cisplatin (PF) (HR [hazard ratios] = 0.71, 95% credible interval [CI]: 0.51-0.99). Nivolumab plus tegafur (S-1) plus oxaliplatin (Nivo-SOX) and tislelizumab plus capecitabine plus oxaliplatin (Tisle-XELOX) were also found to be better than PF in providing OS benefit (HR = 0.73, 95%CI: 0.57-0.93 and HR = 0.74, 95%CI: 0.59-0.93, respectively). Sint-XELOX still provided the best progression-free survival (PFS) (SUCRA, 96%), with significant differences versus PF (HR = 0.47, 95%CI: 0.31-0.69). Nivo-SOX and Tisle-XELOX were also found to be better to PF in providing PFS benefit (HR = 0.58, 95%CI: 0.42-0.80 and HR = 0.67, 95%CI: 0.54-0.82, respectively). CONCLUSIONS: These results indicated that immunotherapy plus chemotherapy was associated with greater progression-free survival and overall survival benefits for patients with HER2-negative advanced gastric cancer, compared with other first-line treatments. In particular, sintilimab combined with chemotherapy showed the best PFS and OS benefits.

Development and Validation of a Clinic Machine Learning Classifier for the Prediction of Risk Stratifications of Prostate Cancer Bone Metastasis Progression to Castration Resistance.

Objective: To explore the predictive factors and predictive model construction for the progression of prostate cancer bone metastasis to castration resistance. Methods: Clinical data of 286 patients diagnosed with prostate cancer with bone metastasis, initially treated with endocrine therapy, and progressing to metastatic castration resistant prostate cancer (mCRPC) were collected. By comparing the differences in various factors between different groups with fast and slow occurrence of castration-resistant prostate cancer (CRPC). Kaplan-Meier survival analysis and COX multivariate risk proportional regression model were used to compare the differences in the time to progression to CRPC in different groups. The COX multivariate risk proportional regression model was used to evaluate the impact of candidate factors on the time to progression to CRPC and establish a predictive model. The accuracy of the model was then tested using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Results: The median time for 286 mCRPC patients to progress to CRPC was 17 (9.5-28.0) months. Multivariate analysis showed that the lowest value of PSA (PSA nadir), the time when PSA dropped to its lowest value (timePSA), and the number of BM, and LDH were independent risk factors for rapid progression to CRPC. Based on the four independent risk factors mentioned above, a prediction model was established, with the optimal prediction model being a random forest with area under curve (AUC) of 0.946[95% CI: 0.901-0.991] and 0.927[95% CI: 0.864-0.990] in the training and validation cohort, respectively. Conclusion: After endocrine therapy, the PSA nadir, timePSA, the number of BM, and LDH are the main risk factors for rapid progression to mCRPC in patients with prostate cancer bone metastases. Establishing a CRPC prediction model is helpful for early clinical intervention decision-making.

Identifying the oral microbiome of adolescents with and without dental fluorosis based on full-length 16S rRNA gene sequencing.

Dental fluorosis, resulting from long-term environmental exposure to fluoride, is prevalent among diverse populations worldwide. Severe fluorosis not only compromises the aesthetic appeal of teeth but also impairs their functionality. This study aims to investigate the oral microbiome in dental fluorosis and the health individuals of adolescents living in the endemic fluorosis area of Guizhou, China through full-length 16S rDNA sequencing. Fourty-six individuals meet the sampling criteria, and we divided these samples into the following groups: a healthy group (H = 23) and a dental fluorosis group (F = 23), and two subgroups of Miao ethnicity: a healthy Miao group (Hm = 13) and a dental fluorosis Miao group (Fm = 15). A total of 660,389 high-quality sequences were obtained, and 12,007 Amplicon Sequence Variants (ASVs) were identified, revealing significant variations in oral microbiome between Fm and Hm groups. The composition of oral microbiota was similar between the H and F groups. At the genus level, Pseudopropionibacterium and at the species level, Streptococcus oralis_subsp.dentisani_clade_058 were less abundant in group F than in group H (P < 0.05). Further analysis revealed that the abundance of Capnocytophaga gingivalis and Kingella denitrificans was significantly lower in Fm fluorosis patients than in the Hm group (P < 0.05). Based on the LEfSe analysis, the potential core biomarkers in the oral of Fm fluorosis patients were identified at different taxonomic levels, ranging from phylum to species. These include Gammaproteobacteria, Prevotella sp_HMT_304, Gemella sanguinis, and Gracilibacteria_(GN02). Network analysis revealed that the microbiota in the fluorosis group exhibited more complex interactions with each other than the healthy group. Notably, within the Hm group, the potential biomarkers Capnocytophaga gingivalis and Kingella denitrificans exhibited a positive correlation. Finally, we employed PICRUSt2 analysis to explore the abundance clustering of the top 30 functional units in each sample, and we found that the metabolic pathway compositions of the four groups were similar. In summary, our findings suggest that the microbial composition of plaque in Hm patients with dental fluorosis is significantly altered, and we identified the potential marker microorganisms that contribute to these changes.

Atorvastatin ameliorated PM2.5-induced atherosclerosis in rats.

PM2.5 provokes atherosclerotic events. Atorvastatin presents anti-inflammatory and antioxidant activities, and may ameliorate PM2.5-induced atherosclerosis development. The purpose of this study was to investigate the cardiotoxic effect of fine particulate matter (PM2.5) on atherosclerosis (AS) in rats, and the intervention effects of atorvastatin (ATO) on PM2.5-induced AS development. AS model was established using 32 male Wistar rats through intraperitoneal injection of vitamin D3 combined with a high-fat diet (10% fat and 4% cholesterol). The rats were randomly divided into 4 groups: control group, PM2.5-exposed group, ATO group, and ATO treated PM2.5-exposed group. PM2.5 increased levels of TC, TG, LDL, MDA, IL-6, and TNF-α, as well as decreased SOD levels. Besides, PM2.5 also enhanced AI. After the treatment of ATO, most levels of various contents in serum, including TC, TG, LDL, MDA, IL-6, TNF-α, hS-CRP, and ox-LDL, significantly decreased compared to the PM2.5-exposed group. Moreover, after the treatment of ATO, AI was significantly reduced compared to the PM2.5-exposed group. In addition, PM2.5 exacerbated the nuclear translocation and ATO resulted in an obvious decrease in PM2.5-induced nuclear translocation. The present study suggests that PM2.5 could induce oxidative damage and systemic inflammatory response in atherosclerosis model rats, while ATO could ameliorate PM2.5-induced atherosclerosis development, possibly by lowering lipid, inhibiting inflammation, and suppressing oxidation.

Potentially Inappropriate Medication Use Among Older Patients with Diabetes in a Chinese Community.

BACKGROUND: Potentially inappropriate medications (PIMs) are frequently prescribed to older people with diabetes. This study aimed to assess the prevalence of PIM use in older people with diabetes and identify potential risk factors influencing the development of PIM use. METHODS: This was a cross-sectional study conducted in an outpatient setting in Beijing, China, using Chinese criteria. The prevalence of PIM use, polypharmacy, and comorbidities in older adults with diabetes in an outpatient setting was measured. Logistic models were employed to investigate the association among polypharmacy, comorbidities, and PIM use. RESULTS: The prevalence of PIM use and polypharmacy was 50.1% and 70.8%, respectively. The most common comorbidities were hypertension (68.0%), hyperlipemia (56.6%), and stroke (36.3%), and the top three inappropriately used medications were insulin (22.0%), clopidogrel (11.9%), and eszopiclone (9.81%). Age (OR 1.025; 95% CI 1.009, 1.042), the number of diagnoses (OR 1.172; 95% CI 1.114, 1.232), coronary heart disease (OR 1.557; 95% CI 1.207, 2.009), and polypharmacy (OR 1.697; 95% CI 1.252, 2.301) were associated with PIM use. CONCLUSIONS: Given the higher rate of PIM use among older adults with diabetes, strategies and interventions targeting this population are needed to minimize PIM use.

Effective TME-related signature to predict prognosis of patients with head and neck squamous cell carcinoma.

Introduction: The tumor microenvironment (TME) is crucial for the development of head and neck squamous cell carcinoma (HNSCC). However, the correlation of the characteristics of the TME and the prognosis of patients with HNSCC remains less known. Methods: In this study, we calculated the immune and stromal cell scores using the "estimate" R package. Kaplan-Meier survival and CIBERSORT algorithm analyses were applied in this study. Results: We identified seven new markers: FCGR3B, IGHV3-64, AC023449.2, IGKV1D-8, FCGR2A, WDFY4, and HBQ1. Subsequently, a risk model was constructed and all HNSCC samples were grouped into low- and high-risk groups. The results of both the Kaplan-Meier survival and receiver operating characteristic curve (ROC) analyses showed that the prognosis indicated by the model was accurate (0.758, 0.756, and 0.666 for 1-, 3- and 5-year survival rates). In addition, we applied the CIBERSORT algorithm to reveal the significant differences in the infiltration levels of immune cells between the two risk groups. Discussion: Our study elucidated the roles of the TME and identified new prognostic biomarkers for patients with HNSCC.