The regional disparities in liver disease comorbidity among elderly Chinese based on a health ecological model: the China Health and Retirement Longitudinal Study.

PURPOSE: This study aimed to investigate the risk factors for liver disease comorbidity among older adults in eastern, central, and western China, and explored binary, ternary and quaternary co-morbid co-causal patterns of liver disease within a health ecological model. METHOD: Basic information from 9,763 older adults was analyzed using data from the China Health and Retirement Longitudinal Study (CHARLS). LASSO regression was employed to identify significant predictors in eastern, central, and western China. Patterns of liver disease comorbidity were studied using association rules, and spatial distribution was analyzed using a geographic information system. Furthermore, binary, ternary, and quaternary network diagrams were constructed to illustrate the relationships between liver disease comorbidity and co-causes. RESULTS: Among the 9,763 elderly adults studied, 536 were found to have liver disease comorbidity, with binary or ternary comorbidity being the most prevalent. Provinces with a high prevalence of liver disease comorbidity were primarily concentrated in Inner Mongolia, Sichuan, and Henan. The most common comorbidity patterns identified were "liver-heart-metabolic", "liver-kidney", "liver-lung", and "liver-stomach-arthritic". In the eastern region, important combination patterns included "liver disease-metabolic disease", "liver disease-stomach disease", and "liver disease-arthritis", with the main influencing factors being sleep duration of less than 6 h, frequent drinking, female, and daily activity capability. In the central region, common combination patterns included "liver disease-heart disease", "liver disease-metabolic disease", and "liver disease-kidney disease", with the main influencing factors being an education level of primary school or below, marriage, having medical insurance, exercise, and no disabilities. In the western region, the main comorbidity patterns were "liver disease-chronic lung disease", "liver disease-stomach disease", "liver disease-heart disease", and "liver disease-arthritis", with the main influencing factors being general or poor health satisfaction, general or poor health condition, severe pain, and no disabilities. CONCLUSION: The comorbidities associated with liver disease exhibit specific clustering patterns at both the overall and local levels. By analyzing the comorbidity patterns of liver diseases in different regions and establishing co-morbid co-causal patterns, this study offers a new perspective and scientific basis for the prevention and treatment of liver diseases.

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01).

Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer. Methods: and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR). Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). Trial registration: This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

The effect of glycopyrrolate vs. atropine in combination with neostigmine on cardiovascular system for reversal of residual neuromuscular blockade in the elderly: a randomized controlled trial.

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.

Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.

Ketamine has demonstrated rapid and sustained antidepressant effects, marking its emergence as an innovative treatment of depression. Despite the growing number of preclinical and clinical studies exploring the antidepressant effects of ketamine and its enantiomers, a comprehensive bibliometric analysis in this field has yet to be conducted. This study employs bibliometric methods and visualization tools to examine the literature and identify key topics related to the antidepressant effects of ketamine and its enantiomers. We sourced publications on the antidepressant effects of ketamine and its enantiomers from the Web of Science Core Collection (WOSCC) database, covering the period from 2000 to 2023. Tools such as VOSviewer, CiteSpace and the R package "bibliometrix" were utilized for visual analysis. The study included 4,274 publications, with a notable increase in publications peaking in 2022. Co-occurrence analysis highlighted two primary research focal points: the efficacy and safety of ketamine and its enantiomers in treating depression, and the mechanisms behind their antidepressant effects. In conclusion, this analysis revealed a significant increase in research on the antidepressant effects of ketamine and its enantiomers over the past two decades, leading to the approval of esketamine nasal spray for treatment-resistant depression. The rapid antidepressant effects of ketamine have spurred further studies into its mechanisms of action and the search for new antidepressants with fewer side effects.

Hairless (Hr) Deficiency Mitigates High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

Obesity is a significant global health concern linked to excessive dietary energy intake. This research focuses on the mammalian hairless protein (HR), known for its role in skin and hair function, and its impact on metabolism. Examining male wild-type (Hr+/+) and Hr null (Hr-/-) mice over a 14-week normal chow diet (NCD) or high-fat diet (HFD) intervention. This study reveals that HR deficiency exhibited a protective effect against HFD-induced obesity and insulin resistance. This protective effect is attributed to increased energy expenditure in Hr-/- mice. Moreover, the brown adipose tissue (BAT) of Hr-/- mice displays elevated levels of the thermogenic protein, uncoupling protein 1 (Ucp1), and its key transcriptional regulators (PPARγ and PGC1α), compared to Hr+/+ mice. In summary, the findings underscore the protective role of HR deficiency in countering HFD-induced adiposity by enhancing insulin sensitivity, raising energy expenditure, and augmenting thermogenic factors in BAT. Further exploration of HR metabolic regulation holds promise for potential therapeutic targets in addressing obesity-related metabolic disorders.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Dense Amorphous Passivation Layer Formed on Aluminum Alloy Surfaces by Femtosecond Laser-Assisted Oxygen-Rich Doping.

Aluminum (Al) alloy surfaces are prone to serious corrosion in humid and salt-laden environments, which promotes the development of numerous protective approaches. Although the amorphous state is more conducive to improve corrosion resistance compared with the crystalline state, it still faces coating design problems like insufficient adhesive strength and flaking-off tendency. Here, we propose a strategy of femtosecond laser-assisted oxygen-rich doping to in situ create a dense high-quality passivation layer on Al alloy surfaces. With respect to the femtosecond laser processing in traditional air ambience, the material surface modifications within the oxygen-rich environment demonstrate some distinctiveness. For the ridge area of the laser ablation grooves, the oxidation surface is separated into two layers: the outer region presents a loose and porous appearance similar to the observations in the air ambience, while the inner region exhibits complete and homogeneous oxidation, especially associated with the continuous distribution of the amorphous substance, in sharp contrast to the nanoscale discrete amorphous formation in the air case. Simultaneously, the high degree of material oxidization with the amorphous phase is also developed on the wallside area of the groove valleys, which is much different from the incomplete oxidation in the air ambience. As a result, the measured corrosion current decreases by 49 times to a value of Icorr = 1.19 × 10-10 A/cm2 relative to the laser treatment in the air environment. Such a method offers the prospect for elevating the anticorrosion performance of metal surfaces.

The immobilization of cadmium by rape straw derived biochar in alkaline conditions: Sorption isotherm, molecular binding mechanism, and in-situ remediation of Cd-contaminated soil.

The issue of cadmium (Cd) contamination in alkaline soils is escalating, necessitating the prompt implementation of effective passivation strategies. Biochar has gained significant attention for its potential in immobilizing heavy metals; however, the suitability of biochar as a remediation material and its micro-scale interaction mechanisms with Cd under alkaline conditions remain unclear. Rape straw (RS) were pyrolyzed at 400°C (RB400) and 700°C (RB700) to produce biochar. Adsorption and soil incubation experiments were carried out to assess the feasibility of using rape straw derived biochar pyrolyze at different temperatures and understanding their remediation mechanisms in alkaline environments. The sorption capacity for Cd immobilization was evaluated using sorption isotherms, revealing that RB700 exhibited enhanced Cd sorption performance with a maximum sorption capacity of 119.33 mg g-1 calculated from the Langmuir isotherm equation at pH 8. Cd L3-edge X-ray sorption near-edge structure (XANES) spectroscopy analysis confirmed that the dominant sorption species of Cd were organic Cd in RB400, with CdCO3 precipitation increased to 73.9% in RB700. Solid-state 13C nuclear magnetic resonance (13C-NMR) spectroscopy demonstrated that aromatic and carboxyl C functional groups are involved in the organic sorption of Cd through complexation and Cd2+-π interactions in alkaline solutions. The precipitation of CdCO3 in RB700 may resulted in a more effective passivation effect compared to RB400, leading to a significant 15.54% reduction in the DTPA-Cd content in Cd-contaminated soil. These findings highlight the effective Cd passivation Cd in alkaline environments by rape straw derived biochar, providing new molecular insights into the Cd retention mechanism of biochar. Furthermore, it presents novel ideas for improving remediation approaches for alkaline Cd-contaminated soils.

Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Efficacy and safety of esketamine for perioperative depression in patients undergoing elective surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a prevalent mood disorder during the perioperative period, with both preoperative concurrent depression and new-onset postoperative depression impacting postoperative recovery. Recent studies have indicated that the dissociative anesthetic esketamine may alleviate perioperative depressive symptoms. OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of esketamine in treating perioperative depression. METHODS: We selected randomized controlled trials comparing esketamine to placebo in terms of postoperative depressive symptoms. The primary outcome was postoperative depression scores, with secondary outcomes including the prevalence of postoperative depression, pain scores using the Visual Analogue Scale or Numeric Rating Scale, and incidences of adverse reactions such as nausea/vomiting, dizziness, dreams/nightmares, hallucinations. RESULTS: We enrolled a total of 17 studies involving 2462 patients. The esketamine group demonstrated a significant reduction in postoperative depression scores within one week after surgery (SMD -0.47, 95% CI (-0.66, -0.27), P < 0.001) and over the long term (SMD -0.44, 95% CI (-0.79, -0.09), P = 0.01). Furthermore, esketamine significantly decreased the prevalence of postoperative depression both within one week (RR 0.46, 95% CI (0.33, 0.63), P < 0.001) and over the long term (RR 0.50, 95% CI (0.36, 0.70), P < 0.001). Additionally, esketamine effectively relieved pain on the first postoperative day compared to control. However, it also increased the risks of dizziness and hallucinations for a short time. CONCLUSION: This meta-analysis suggests that the intraoperative or postoperative application of esketamine could be a potentially effective treatment for perioperative depression, although the increased risk of adverse reactions should be considered.

Causal relationship of obesity and adiposity distribution on risk of ventral hernia.

PURPOSE: Ventral hernia (VH) is a common surgical disease. Previous studies suggested that obesity is an important risk factor for VH. However, the causal relationship between fat distribution and the risk of VH is still unclear. This study used Mendelian randomization (MR) to evaluate their causal relationship. METHODS: We used the body mass index (BMI), body fat percentage, and body fat mass to represent general obesity and utilized the volume of abdominal subcutaneous adiposity tissue, visceral adiposity tissue, waist circumference, hip circumference, and waist-to-hip ratio to represent abdominal adiposity. The data were extracted from the large-scale genome-wide association study of European ancestry. We used two-sample MR to infer causality, using multivariate MR to correct the effects of confounding factors. RESULTS: Increased BMI, body fat percentage, body fat mass, visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or waist-to-hip ratio, were causally associated with a higher risk of VH. The results of multivariate MR suggested that body fat percentage was causally associated with a higher risk of VH after adjusting for body mass index, diabetes, and smoking. CONCLUSION: General obesity, increased visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or the waist-to-hip ratio were causally associated with a higher risk of VH. These findings provided a deeper understanding of the role that the distribution of adiposity plays in the mechanism of VH.

Sympathetic innervation induces exosomal miR-125 transfer from osteoarthritic chondrocytes, disrupting subchondral bone homeostasis and aggravating cartilage damage in aging mice.

INTRODUCTION: Osteoarthritis (OA) is a progressive disease that poses a significant threat to human health, particularly in aging individuals: Although sympathetic activation has been implicated in bone metabolism, its role in the development of OA related to aging remains poorly understood. Therefore, this study aimed to investigate how sympathetic regulation impacts aging-related OA through experiments conducted both in vivo and in vitro. METHODS: To analyze the effect of sympathetic regulation on aging-related OA, we conducted experiments using various mouse models. These models included a natural aging model, a medial meniscus instability model, and a load-induced model, which were used to examine the involvement of sympathetic nerves. In order to evaluate the expression levels of ß1-adrenergic receptor (Adrß1) and sirtuin-6 (Sirt6) in chondrocytes of naturally aging OA mouse models, we performed assessments. Additionally, we investigated the influence of ß1-adrenergic receptor knockout or treatment with a ß1-adrenergic receptor blocker on the progression of OA in aging mice and detected exosome release and detected downstream signaling expression by inhibiting exosome release. Furthermore, we explored the impact of sympathetic depletion through tyrosine hydroxylase (TH) on OA progression in aging mice. Moreover, we studied the effects of norepinephrine(NE)-induced activation of the ß1-adrenergic receptor signaling pathway on the release of exosomes and miR-125 from chondrocytes, subsequently affecting osteoblast differentiation in subchondral bone. RESULTS: Our findings demonstrated a significant increase in sympathetic activity, such as NE levels, in various mouse models of OA including natural aging, medial meniscus instability, and load-induced models. Notably, we observed alterations in the expression levels of ß1-adrenergic receptor and Sirt6 in chondrocytes in OA mouse models associated with natural aging, leading to an improvement in the progression of OA. Critically, we found that the knockout of ß1-adrenergic receptor or treatment with a ß1-adrenergic receptor blocker attenuated OA progression in aging mice and the degraded cartilage explants produced more exosome than the nondegraded ones, Moreover, sympathetic depletion through TH was shown to ameliorate OA progression in aging mice. Additionally, we discovered that NE-induced activation of the ß1-adrenergic receptor signaling pathway facilitated the release of exosomes and miR-125 from chondrocytes, promoting osteoblast differentiation in subchondral bone. CONCLUSION: In conclusion, our study highlights the role of sympathetic innervation in facilitating the transfer of exosomal miR-125 from osteoarthritic chondrocytes, ultimately disrupting subchondral bone homeostasis and exacerbating cartilage damage in aging mice. These findings provide valuable insights into the potential contribution of sympathetic regulation to the pathogenesis of aging-related OA.

A predictive model for post-thoracoscopic surgery pulmonary complications based on the PBNN algorithm.

We constructed an early prediction model for postoperative pulmonary complications after thoracoscopic surgery using machine learning and deep learning algorithms. The artificial intelligence prediction models were built in Python, primarily using artificial intelligencealgorithms including both machine learning and deep learning algorithms. Correlation analysis showed that postoperative pulmonary complications were positively correlated with age and surgery duration, and negatively correlated with serum albumin. Using the light gradient boosting machine(LGBM) algorithm, weighted feature engineering revealed that single lung ventilation duration, history of smoking, surgery duration, ASA score, and blood glucose were the main factors associated with postoperative pulmonary complications. Results of artificial intelligence algorithms for predicting pulmonary complications after thoracoscopy in the test group: In terms of accuracy, the two best algorithms were Logistic Regression (0.831) and light gradient boosting machine(0.827); in terms of precision, the two best algorithms were Gradient Boosting (0.75) and light gradient boosting machine (0.742); in terms of recall, the three best algorithms were gaussian naive bayes (0.581), Logistic Regression (0.532), and pruning Bayesian neural network (0.516); in terms of F1 score, the two best algorithms were LogisticRegression (0.589) and pruning Bayesian neural network (0.566); and in terms of Area Under Curve(AUC), the two best algorithms were light gradient boosting machine(0.873) and pruning Bayesian neural network (0.869). The results of this study suggest that pruning Bayesian neural network (PBNN) can be used to assess the possibility of pulmonary complications after thoracoscopy, and to identify high-risk groups prior to surgery.

Artificial intelligence algorithms for predicting post-operative ileus after laparoscopic surgery.

Objective: By constructing a predictive model using machine learning and deep learning technologies, we aim to understand the risk factors for postoperative intestinal obstruction in laparoscopic colorectal cancer patients, and establish an effective artificial intelligence-based predictive model to guide individualized prevention and treatment, thus improving patient outcomes. Methods: We constructed a model of the artificial intelligence algorithm in Python. Subjects were randomly assigned to either a training set for variable identification and model construction, or a test set for testing model performance, at a ratio of 7:3. The model was trained with ten algorithms. We used the AUC values of the ROC curves, as well as accuracy, precision, recall rate and F1 scores. Results: The results of feature engineering composited with the GBDT algorithm showed that opioid use, anesthesia duration, and body weight were the top three factors in the development of POI. We used ten machine learning and deep learning algorithms to validate the model, and the results were as follows: the three algorithms with best accuracy were XGB (0.807), Decision Tree (0.807) and Neural DecisionTree (0.807); the two algorithms with best precision were XGB (0.500) and Decision Tree (0.500); the two algorithms with best recall rate were adab (0.243) and Decision Tree (0.135); the two algorithms with highest F1 score were adab (0.290) and Decision Tree (0.213); and the three algorithms with best AUC were Gradient Boosting (0.678), XGB (0.638) and LinearSVC (0.633). Conclusion: This study shows that XGB and Decision Tree are the two best algorithms for predicting the risk of developing ileus after laparoscopic colon cancer surgery. It provides new insight and approaches to the field of postoperative intestinal obstruction in colorectal cancer through the application of machine learning techniques, thereby improving our understanding of the disease and offering strong support for clinical decision-making.

Arsenic(III) sorption on organo-ferrihydrite coprecipitates: Insights from maize and rape straw-derived DOM.

The mobility of arsenic (As) specie in agricultural soils is significantly impacted by the interaction between ferrihydrite (Fh) and dissolved organic material (DOM) from returning crop straw. However, additional research is necessary to provide molecular evidence for the interaction of toxic and mobile As (As(III)) specie and crop straw-based organo- Fh coprecipitates (OFCs). This study investigated the As(III) sorption behaviours of OFCs synthesized with maize or rape derived-DOM under various environmental conditions and the primary molecular sorption mechanisms using As K-edge X-ray absorption near edge structure (XANES) spectroscopy. According to our findings, pure Fh adsorbed more As(III) relative to the other two OFCs, and the presence of natural organic matter in the OFCs induced more As(III) adsorption at pH 5.0. Findings from this study indicated a maximum As(III) sorption on Ma (53.71 mg g⁻1) and Ra OFC (52.46 mg g⁻1) at pH 5.0, with a sharp decrease as the pH increased from 5.0 to 8.0. Additionally, As K-edge XANES spectroscopy indicated that ∼30% of adsorbed As(III) on the OFCs undergoes transformation to As(V) at pH 7-8. Functional groups from the DOM, such as O-H, COOH, and CO, contributed to As(III) desorption and its oxidation to As(V), whereas ionic strength analysis revealed inner complexation as the dominant As(III) sorption mechanism on the OFCs. Overall, the results indicate that the interaction of natural organic matter (NOM) with As(III) at higher pH promotes As(III) mobility, which is crucial when evaluating As migration and bioavailability in alkaline agricultural soils.

Causal association between genetically predicted circulating immune cell counts and frailty: a two-sample Mendelian randomization study.

Background: Despite the recognized link between immune responses and frailty, the association between immune cell counts and frailty based on previous observational studies remains disputed, with uncertain causal nexus. This study aimed to elucidate causal association between genetically predicted circulating immune cell counts and frailty. Methods: We conducted the two-sample Mendelian randomization (MR) study with independent genetic variants associated with six immune cell subtype counts from genome-wide association studies in 563,946 European individuals. Frailty summary data, assessed via frailty index (FI), was obtained from study comprising 175,226 subjects. Univariate MR, reverse MR and multivariate MR were conducted to comprehensive investigate the association between immune cell counts and FI, with two-step MR analysis for mediation analysis. Results: Univariate MR evidence indicated that among six leukocyte subtype counts, only elevated eosinophil count was significantly correlated with higher FI (ß = 0.059, 95% confidence interval [CI], 0.042-0.078, P=5.63E-11), with no reverse causal relationship identified in reverse MR. In multivariate MR, the causal effect of eosinophil count retained statistical significance (ß = 0.063, 95% CI, 0.021-0.104, P = 0.003). Ultimately, the two-step MR analysis demonstrated two mediators in this causal pathway: asthma (ß= 0.019, 95% CI, 0.013-0.025, P = 35.84E-10, mediated proportion, 31.732%) and rheumatoid arthritis (ß= 0.004, 95% CI, 0.001-0.006, P=1.75E-03, mediated proportion, 6.411%). Conclusions: Within immune cell subtypes, MR evidence indicated only genetically predicted circulating eosinophil count had irreversible and independent causal effect on frailty, with asthma and rheumatoid arthritis possibly serving as partial mediators. The finding stressed the need for further exploring physiological functions of eosinophils in order to develop effective strategies against frailty.

Repeated (S)-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota-brain axis.

Chronic pain is commonly linked with diminished working memory. This study explores the impact of the anesthetic (S)-ketamine on spatial working memory in a chronic constriction injury (CCI) mouse model, focusing on gut microbiome. We found that multiple doses of (S)-ketamine, unlike a single dose, counteracted the reduced spontaneous alteration percentage (%SA) in the Y-maze spatial working memory test, without affecting mechanical or thermal pain sensitivity. Additionally, repeated (S)-ketamine treatments improved the abnormal composition of the gut microbiome (ß-diversity), as indicated by fecal 16S rRNA analysis, and increased levels of butyrate, a key gut - brain axis mediator. Protein analysis showed that these treatments also corrected the upregulated histone deacetylase 2 (HDAC2) and downregulated brain-derived neurotrophic factor (BDNF) in the hippocampi of CCI mice. Remarkably, fecal microbiota transplantation from mice treated repeatedly with (S)-ketamine to CCI mice restored %SA and hippocampal BDNF levels in CCI mice. Butyrate supplementation alone also improved %SA, BDNF, and HDAC2 levels in CCI mice. Furthermore, the TrkB receptor antagonist ANA-12 negated the beneficial effects of repeated (S)-ketamine on spatial working memory impairment in CCI mice. These results indicate that repeated (S)-ketamine administration ameliorates spatial working memory impairment in CCI mice, mediated by a gut microbiota - brain axis, primarily through the enhancement of hippocampal BDNF - TrkB signaling by butyrate.

Risk factors of liver abscess and biloma formation after drug-eluting bead transarterial chemoembolization for unresectable intrahepatic cholangiocarcinoma.

BACKGROUND AND STUDY AIMS: Drug-eluting bead transarterial chemoembolization (DEB-TACE) causes serious complications, including liver abscess and biloma formation. This study aimed to investigate the frequency and risk factors of liver abscess and biloma formation after dug-eluting bead transarterial chemoembolization for unresectable intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: 152 unresectable ICC patients received 241 DEB-TACE procedures from February 2018 to November 2022 were studied retrospectively. Patients were evaluated for the presence of liver abscess and biloma formation after DEB-TACE. The medical records, including baseline demographic data, preoperative imaging data, DEB-TACE details, and postoperative management, were reviewed to search for risk factors of liver abscess and biloma formation. RESULTS: Liver abscesses developed in 11 cases, with an incidence rate of 7.2 % (11/152) per patient and 4.6 % (11/241) per procedure. In the 11 patients with abscesses, the incidence of biloma formation was 36.4 % (n = 4). The binary logistic regression analysis showed that diabetes mellitus (OR 7.967, 95 % CI 1.491-42.571, p = 0.015), bilioenterostomy or biliary stent implantation (OR 18.716, 95 % CI 1.006-348.049, p = 0.049) and grade 1 arterial occlusion (OR 9.712, 95 % CI 1.054-89.484, p = 0.045) were independent risk factors for liver abscess and biloma formation. CONCLUSION: Liver abscesses and biloma formation induced by DEB-TACE are associated with various factors. Diabetes mellitus, bilioenterostomy or biliary stent implantation, and grade 1 artery occlusion were all associated with liver abscess and biloma formation after DEB-TACE for unresectable ICC. In patients with these risk factors, the DEB-TACE procedure should be finely designed and manipulated with more caution.