Predicting academic achievement from the collaborative influences of executive function, physical fitness, and demographic factors among primary school students in China: ensemble learning methods.

BACKGROUND: Elevated levels of executive function and physical fitness play a pivotal role in shaping future quality of life. However, few studies have examined the collaborative influences of physical and mental health on academic achievement. This study aims to investigate the key factors that collaboratively influence primary school students' academic achievement from executive function, physical fitness, and demographic factors. Additionally, ensemble learning methods are employed to predict academic achievement, and their predictive performance is compared with individual learners. METHODS: A cluster sampling method was utilized to select 353 primary school students from Huai'an, China, who underwent assessments for executive function, physical fitness, and academic achievement. The recursive feature elimination cross-validation method was employed to identify key factors that collaboratively influence academic achievement. Ensemble learning models, utilizing eXtreme Gradient Boosting and Random Forest algorithms, were constructed based on Bagging and Boosting methods. Individual learners were developed using Support Vector Machine, Decision Tree, Logistic Regression, and Linear Discriminant Analysis algorithms, followed by the establishment of a Stacking ensemble learning model. RESULTS: Our findings revealed that sex, body mass index, muscle strength, cardiorespiratory function, inhibition, working memory, and shifting were key factors influencing the academic achievement of primary school students. Moreover, ensemble learning models demonstrated superior predictive performance compared to individual learners in predicting academic achievement among primary school students. CONCLUSIONS: Our results suggest that recognizing sex differences and emphasizing the simultaneous development of cognition and physical well-being can positively impact the academic development of primary school students. Ensemble learning methods warrant further attention, as they enable the establishment of an accurate academic early warning system for primary school students.

Autophagy and PPARs/NF-κB-associated inflammation are involved in hepatotoxicity induced by the synthetic phenolic antioxidant 2,4-di-tert-butylphenol in common carp (Cyprinus carpio).

The synthetic phenolic antioxidant 2,4-di-tert-butylphenol (2,4-DTBP) is an emergent contaminant and can disrupt the delicate balance of aquatic ecosystems. This study aimed to investigate 2,4-DTBP-induced hepatotoxicity in common carp and the underlying mechanisms involved. Sixty common carp were divided into four groups and exposed to 0 mg/L, 0.01 mg/L, 0.1 mg/L or 1 mg/L 2,4-DTBP for 30 days. Here, we first demonstrated that 2,4-DTBP exposure caused liver damage, manifested as hepatocyte nuclear pyknosis, inflammatory cell infiltration and apoptosis. Moreover, 2,4-DTBP exposure induced hepatic reactive oxygen species (ROS) overload and disrupted antioxidant capacity, as indicated by the reduced activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). In addition, transmission electron microscopy revealed that 2,4-DTBP exposure induced autophagosome accumulation in the liver of common carp. Western blot analysis further revealed that 2,4-DTBP exposure significantly decreased the protein levels of mTOR and increased the LC3II/LC3I ratio. Furthermore, 2,4-DTBP exposure inhibited lysozyme (LZM) and alkaline phosphatase (AKP) activity; decreased immunoglobulin M (IgM), complement 3 (C3), and complement 4 (C4) levels in the serum; increased the mRNA levels of proinflammatory cytokines (NF-κB, TNF-α, IL-1ß and IL-6); and increased the mRNA levels of three types of proliferator-activated receptors (PPARs) (α, ß/δ and γ). Molecular docking revealed that 2,4-DTBP directly binds to the internal active pocket of PPARs. Overall, we concluded that 2,4-DTBP exposure in aquatic systems could induce hepatotoxicity in common carp by regulating autophagy and controlling inflammatory responses. The present study provides new insights into the hepatotoxicity mechanism induced by 2,4-DTBP in aquatic organisms and furthers our understanding of the effects of 2,4-DTBP on public health and ecotoxicology.

A Case of Severe Lethal Allergic Reaction Caused by Iodixanol After Digital Subtraction Angiography.

BACKGROUND: Severe lethal allergic reactions triggered by iodixanol following digital subtraction angiography (DSA) are rare. The majority of skin reactions associated with iodixanol were mild, and the prognosis was favorable. Moreover, a case of serious skin adverse events caused by iodixanol has been documented. METHODS: A 61-year-old woman underwent surgery for a cerebral hemorrhage in another hospital. Upon the surgery, the patient's state of impaired consciousness did not show any improvement. Head computed tomography angiography on admission: right middle cerebral artery M1 segment enlargement, left posterior cerebral artery P2 stenosis. Following undergoing DSA with iodixanol, the patient experienced severe and fatal drug eruptions, which represents a serious and uncommon complication associated with iodixanol. RESULTS: This paper describes the experience in the treatment and nursing of severe allergic reactions. Despite the fact that the patient was discharged automatically and eventually died, there are valuable lessons to be learned from this case that can inform and guide future clinical practices. CONCLUSIONS: Iodixanol adverse reactions were rare, and severe fatal adverse reactions were seldom reported. Consequently, the authors conclude that the potential adverse reaction risk of iodixanol contrast agent should be taken into consideration in future endeavors, and the skin and allergy of patients should be monitored following DSA. In an allergy, prompt and proactive treatment is essential to prevent worsening and dissemination.

An Enhanced Neural Network Algorithm with Quasi-Oppositional-Based and Chaotic Sine-Cosine Learning Strategies.

Global optimization problems have been a research topic of great interest in various engineering applications among which neural network algorithm (NNA) is one of the most widely used methods. However, it is inevitable for neural network algorithms to plunge into poor local optima and convergence when tackling complex optimization problems. To overcome these problems, an improved neural network algorithm with quasi-oppositional-based and chaotic sine-cosine learning strategies is proposed, that speeds up convergence and avoids trapping in a local optimum. Firstly, quasi-oppositional-based learning facilitated the exploration and exploitation of the search space by the improved algorithm. Meanwhile, a new logistic chaotic sine-cosine learning strategy by integrating the logistic chaotic mapping and sine-cosine strategy enhances the ability that jumps out of the local optimum. Moreover, a dynamic tuning factor of piecewise linear chaotic mapping is utilized for the adjustment of the exploration space to improve the convergence performance. Finally, the validity and applicability of the proposed improved algorithm are evaluated by the challenging CEC 2017 function and three engineering optimization problems. The experimental comparative results of average, standard deviation, and Wilcoxon rank-sum tests reveal that the presented algorithm has excellent global optimality and convergence speed for most functions and engineering problems.

Fast and simple calibration of frequency response and IQ skew for a coherent optical transmitter using a low-bandwidth photodetector.

A fast, precise, and low-cost coherent optical transmitter calibration scheme is proposed that uses multi-tone signals of a novel, to the best of our knowledge, design with unequal frequency intervals. With a single measurement, the proposed scheme can simultaneously calibrate the frequency response and the IQ skew of the transmitter using only a low-bandwidth photodiode. Simulation and experimental results indicate that the measurement error in the frequency response and coherent transmitter (Tx) skew is less than 0.3 dB and 0.2 ps, respectively. The feasibility of the proposed scheme is verified by an experiment involving 25 Gbaud 16-quadrature amplitude modulation (QAM) signal transmission using a Kramers-Kronig (KK) receiver. With the help of this calibration method, the measured bit error ratio performance was increased from 1.77e-2 to 3.52e-3 when the received optical power was -8 dBm.

Triclocarban evoked neutrophil extracellular trap formation in common carp (Cyprinus carpio L.) by modulating SIRT3-mediated ROS crosstalk with ERK1/2/p38 signaling.

Triclocarban (TCC), an antimicrobial ingredient in personal care products, is associated with immunosuppression and physiological dysfunctions of aquatic organisms. The aim of this study was to investigate whether TCC can induce common carp NETosis (neutrophil death by neutrophil extracellular trap (NET) release) and then to attempt to identify the potential molecular mechanisms. Herein, scanning electron microscopy and flow cytometric assays showed that revealed that TCC triggers DNA-containing web-like structures and increases extracellular DNA content. In the proteomic analysis, we observed that NET-related proteins, extracellular regulated protein kinase (Mapk1, Mapk14, Jak2) and apoptotic protein (caspase3) were significantly increased, and defender against cell death 1 (Dad1) was significantly decreased after TCC treatments. Meanwhile, we confirmed that TCC stress can trigger NETosis in common carp by activating the reactive oxygen species (ROS)/ERK1/2/p38 signaling. We think that the upregulated NDUFS1 expression is closely related to oxidative stress induced by TCC. Importantly, we discovered that SIRT3 expression was significantly decreased in the process of TCC-induced NETs. Importantly, pretreatment with the SIRT3 agonist honokiol (HKL) effectively suppressed TCC-induced NET release. In contrast, the SIRT3 antagonist 3-TYP escalated TCC-induced NET formation. Mechanistically, SIRT3 degradation serves as a potential mediator for regulating oxidative stress crosstalk between ERK1/2/p38 signals in the process of TCC-induced NET formation. These findings unveil new insights into the TCC-evoked health risk of fish and other aquatic organisms and suggest that SIRT3 is a potential pharmacological intervention target to alleviate TCC-induced common carp NETosis.

DSP-free remote antenna unit in a coherent radio over fiber mobile fronthaul for 5G mm-wave mobile communication.

We propose a novel coherent analog radio over fiber (A-RoF) scheme to realize the generation, separation, and detection of four-independent mm-wave signals with the same carrier frequency on a single-wavelength for 5th generation (5G) mobile communication, and no digital signal processing (DSP) algorithms are required in remote antenna unit (RAU). In baseband unit (BBU), four-independent mm-wave signals are modulated on the two orthogonal polarization states of a single wavelength based on a dual-polarization IQ modulator using the dual single-sideband (SSB) modulation and polarization division multiplexing (PDM) technique. In RAU, a novel carrier polarization rotation module based on the self-polarization stabilization technique is proposed, and thus the four-independent mm-wave signals can be detected by self-coherent detection. Besides, the power fading effect induced by the chromatic dispersion could be overcome thanks to the optical SSB modulation, contributing to the increased coverage. By these means, no DSP algorithms are required in RAU, and the latency of signal processing could be significantly reduced. The experimental results show our proposed scheme could support 38.4 Gbps 16-ary quadrature amplitude modulation (16QAM) signals at 14 GHz over 30 km standard single-mode fiber (SSMF) transmission without DSP, satisfying 3rd Generation Partnership Project (3GPP) requirements. Besides, the measured error vector magnitude (EVM) value of 800 MBaud 16QAM signals at 28 GHz over 50 km SSMF transmission is 12.99%. This research provides a potential solution for the 5G mobile fronthaul.

Circular RNA expression profile in transgenic diabetic mouse kidneys.

BACKGROUND: Diabetic nephropathy is one of the most important complications in patients with diabetes. The etiology and pathogenesis of diabetic nephropathy remain unclear. Several studies have indicated that circular RNAs (circRNAs) play crucial regulatory roles in numerous human diseases and normal physiology; however, to date, no study has focused on the comprehensive expression profile of circRNAs in the kidneys of diabetic mice. Therefore, we aimed to identify differentially expressed circRNAs in diabetic mouse kidneys to explore the possible roles of dysregulated circRNAs in diabetic nephropathy development. RESULTS: Diabetic BKS-Leprem2Cd479/Nju (BKS-DB/Nju) mice and their nondiabetic wild-type littermates of C57BL/KsJ wild-type (WT) mice were used as experimental animals. Among all circRNAs identified by high-throughput RNA sequencing, four circRNAs were upregulated and ten were downregulated in diabetic mouse kidneys compared to those in nondiabetic mouse kidneys. After verification using quantitative reverse transcriptase polymerase chain reaction assays, we found that circR_1084, circR_182, circR_4, circR_50, circR_596, circR_897, and circR_203 were downregulated, whereas circR_627, circR_628, circR_735, and circR_801 were upregulated in the renal tissues of 8- and 16-week-old BKS-DB/Nju mice compared to those in WT mice. CONCLUSION: We studied the circRNA expression profile in the kidneys of diabetic mice. Differentially expressed circRNAs may be useful as candidate biomarkers for diabetic nephropathy. Collectively, our results provide a novel theoretical basis for further investigation of the regulatory roles of circRNA in the etiology and pathogenesis of diabetic nephropathy.

The evaluation of bone marrow edema in sacroiliac joint in patients with ankylosing spondylitis using magnetic resonance imaging Dixon sequence.

BACKGROUND: Bone marrow edema of the sacroiliac joint is the early imaging manifestation, an indicator of inflammatory activity of ankylosing spondylitis (AS) (Yang R, et. al. Medicine (Baltimore) 98:e14620, 2019). OBJECTIVE: The aim of the study was to investigate the value of magnetic resonance imaging (MRI) Dixon sequence in the diagnosis of marrow edema of the sacroiliac joint in patients with AS. METHODS: Forty-five patients with AS admitted in our hospital between November 2016 and February 2019 were selected retrospectively as the case group. Forty-five healthy subjects recruited between November 2016 and February 2019 served as the control group. Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were recorded after admission to the hospital. The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were compared with indicators above in order to find the correlation. RESULTS: The water-fat ratio under the bilateral sacroiliac joints on Dixon sequence images in the case group was significantly higher than that in the healthy control group (P<0.05). The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were positively correlated with spinal arthritis research (SPARCC), BASFI and BASDAI score (all P < 0.05), but did not correlate with ESR and CRP. CONCLUSION: The water-fat ratio of magnetic resonance Dixon sequence can be used as a reference index to evaluate the degree of bone marrow edema in active stage of sacroiliac arthritis.

Working memory network plasticity after exercise intervention detected by task and resting-state functional MRI.

The current study examined the effects of an 11-week exercise intervention on brain activity during a working memory (WM) task and resting-state functional network connectivity in deaf children. Twenty-six deaf children were randomly assigned to either an 11-week exercise intervention or control conditions. Before and after the exercise intervention, all participants were scanned with functional magnetic resonance imaging (fMRI) during N-back task performance and a resting state. The behavioural results showed that the exercise intervention improved WM performance. Task activation analyses showed an increase in the parietal, occipital, and temporal gyri and hippocampus and hippocampus (HIP). In addition, WM performance improvements were associated with greater activation in the left HIP region. Resting-state functional connectivity (Rs-FC) between HIP and certain other brain areas shown a significant interaction of group (exercise versus no exercise) and time (pre- and postintervention). Moreover, connectivity between the left HIP and left middle frontal gyrus was related to improved WM performance. These data extend current knowledge by indicating that an exercise intervention can improve WM in deaf children, and these enhancements may be related to the WM network plasticity changes induced by exercise.

The association between maternal methylenetetrahydrofolate reductase C677T and A1298C polymorphism and birth defects and adverse pregnancy outcomes.

Published studies indicate the MTHFR C677T and A1298C polymorphisms are associated with abnormal homocysteine levels, which may cause various pregnancy complications and birth defects. However, the results obtained from different studies have been inconsistent. Therefore, this meta-analysis explores the association between MTHFR polymorphisms and birth defects and adverse pregnancy outcomes. The PubMed, ScienceDirect, Embase, and China Biology Medicine literature databases and ClinicalTrials were searched. Analyses of public bias, meta-regression, subgroups, and sensitivity were used to ensure the robustness of our results. MTHFR C677T was significantly associated with recurrent pregnancy loss in developing countries (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.20-1.50) but not in developed countries (OR, 0.87; 95% CI, 0.68-1.11). No significant relationship was found between MTHFR A1298C and recurrent pregnancy loss (OR, 1.04; 95% CI, 0.93-1.18). MTHFR C677T and A1298C were not associated with preeclampsia (OR, 1.06; 95% CI, 0.97-1.16 and OR, 1.16; 95% CI, 0.97-1.39, respectively), and C677T was not associated with placental abruption (OR, 1.03; 95% CI, 0.87-1.21), intrauterine growth retardation (OR, 1.02; 95% CI, 0.90-1.15), or congenital heart disease (OR, 1.05; 95% CI, 0.89-1.25). MTHFR C677T, but not A1298C, was associated with neural tube defects (OR, 1.24; 95% CI, 1.08-1.42) and Down syndrome (OR, 1.65; 95% CI, 1.39-1.95). CONCLUSION: Although MTHFR C677T and A1298C are significantly associated with some types of congenital defects and adverse pregnancy outcomes, the impact of these polymorphisms is moderate.

Sevelamer hydrochloride suppresses proliferation of parathyroid cells during the early phase of chronic renal failure in rats.

AIM: We examined the effects of sevelamer on parathyroid cell proliferation and secondary hyperparathyroidism in rats following induction of early-phase of chronic renal failure (CRF) by unilateral ureteral obstruction (UUO). METHODS: For 5 days, rats in the control group received normal food, rats in the sevelamer group (SH) received control food plus 5% sevelamer, and rats in the low protein group (LP) received low protein food. Five rats of each group were killed at baseline (day 0). All other rats were given UUO, and five rats per group were killed on days 3, 7, 14, and 28 after UUO. Changes in body weight, serum phosphorus, calcium, intact-parathyroid hormone (i-PTH), creatinine (SCr), creatinine clearance rate (CCR), blood urea nitrogen (BUN), and 24-h urinary phosphorus were determined. Parathyroid tissues were removed for histological examination of proliferating cell nuclear antigen-positive (PCNA+) cells. RESULTS: Measurement of body weight, BUN, and SCr in the controls indicated successful establishment of this model of early-phase CRF. The controls also had remarkable proliferation of PCNA+ cells beginning on day 3, but this did not occur in the SH or LP groups. After 28 days, serum phosphorus had decreased more in the SH and LP groups than in the control group, and phosphorus excretion was much greater in the control group than in the SH and LP groups. The three groups had similar increases in serum i-PTH. CONCLUSION: Sevelamer rapidly lowered the serum phosphorus and inhibited the proliferation of PCNA+ cells in this experimental model of early-phase CRF.

Discovery of 1-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one, an orally active multi-target agent for the treatment of diabetic nephropathy.

Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC50 of 90µM in NIH3T3 cell lines, t1/2 of 4.89±1.33h in male rats and LD50>2000mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN.

Aerobic Exercise Intervention Alters Executive Function and White Matter Integrity in Deaf Children: A Randomized Controlled Study.

This study examined the effects of an 11-week aerobic exercise intervention on executive function (EF) and white matter integrity (WMI). In total, 28 deaf children (aged 9-13 years) were randomly assigned to either an 11-week exercise intervention or the control group. All the children had behavioral assessment and diffusion tensor imaging prior to and following the exercise intervention. The behavioral performance results demonstrated that EF was enhanced by exercise. Relative to the control group, WMI of the exercise intervention group showed (1) lower fractional anisotropy (FA) in the pontine crossing tract (PCT) and right cingulum (hippocampus) (CH), genu of the corpus callosum (gCC), right inferior cerebellar peduncle (ICP), left superior corona radiata (SCR), and left superior frontooccipital fasciculus (SFOF); (2) higher mean diffusivity (MD) in the gCC, right CH, right inferior frontooccipital fasciculus (IFOF), and left anterior limb of the internal capsule (ALIC); and (3) lower MD in the left ICP and left tapetum (TAP). Furthermore, the lower FA in gCC showed a significant negative correlation with improvement in behavioral performance, but the correlation was not significant after FDR correction. These results suggest that exercise can effectively improve deaf children's EF and reshape the WMI in deaf children. The improved EF by exercise is not related to a reshaping of WMI, but more studies on the relationship between EF and WMI by exercise may be needed.

Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review.

To clarify the effects of MTHFR C677T polymorphism on the risk of diabetic nephropathy (DN) in the Chinese population, an updated meta-analysis was performed. Related studies were identified from PubMed, Springer Link, Ovid and Chinese Databases up to 24 February 2015. A total of 15 studies including 1227 DN cases, 586 healthy controls and 1277 diabetes mellitus (DM) controls were involved in this meta-analysis. Overall, a significantly elevated risk of DN was associated with all variants of MTHFR C677T when compared with the healthy group (T vs C, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.88-2.61; TT vs CC, OR = 4.22, 95% CI = 3.02-5.90; TT + CT vs CC, OR = 2.62, 95% CI = 2.07-3.31; TT vs CC + CT, OR = 2.81, 95% CI = 2.08-3.81) or DM (T vs C, OR = 1.78, 95% CI = 1.59-2.00; TT vs CC, OR = 2.95, 95% CI = 2.33-3.73; TT + CT vs CC, OR = 1.93, 95% CI = 1.63-2.29; TT vs CC + CT, OR = 2.31, 95% CI = 1.87-2.84). In subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. This meta-analysis showed that the MTHFR C677T variants may influence DN risk in Chinese, and further studies with gene-gene and gene-environment interactions are required for definite conclusions.

[Clinical study of optimal positive end-expiratory pressure titration guided by lung stretch index in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the clinical practicability of positive end-expiratory pressure (PEEP) titrated by lung stretch index (SI) in patients with acute respiratory distress syndrome (ARDS). METHODS: A parallel randomized controlled trial was conducted. Patients with moderate to severe ARDS who required mechanical ventilation admitted to the department of critical care medicine of General Hospital of the Yangtze River Shipping from August 2022 to February 2023 were enrolled. They were randomly divide into SI guided PEEP titration group (SI group) and pressure-volume curve (P-V curve) inspiratory low inflection point (LIP) guided PEEP titration group (LIP group). All patients were ventilated in a supine position after admission, with the head of the bed raised by 30 degree angle. The primary disease was actively treated, prone position ventilation for 12 h/d, and lung protective ventilation strategies such as controlled lung expansion were used for lung recruitment. On this basis, mechanical ventilation parameters were titrated with SI in the SI group; the LIP group titrated mechanical ventilation parameters with P-V curve inspiratory LIP+2 cmH2O (1 cmH2O≈0.098 kPa). The oxygenation index (PaO2/FiO2), and respiratory mechanics indicators such as lung dynamic compliance (Cdyn), peak airway pressure (Pip) were monitored before recruitment maneuver and after 1, 3, and 5 days of treatment. The therapeutic effect of the two groups was compared. RESULTS: There were 41 patients in the SI group and 40 patients in the LIP group. There was no significant difference in general information such as gender, age, and disease type between the two groups. The mechanical ventilation time and the length of intensive care unit (ICU) stay in the SI group were significantly shorter than those in the LIP group (days: 9.47±3.36 vs. 14.68±5.52, 22.27±4.68 vs. 27.57±9.52, both P < 0.05). Although the 28-day mortality of the SI group was lower than that of the LIP group, the difference was not statistically significant [19.5% (8/41) vs. 35.0% (14/40), P > 0.05]. On the fifth day, the PaO2/FiO2 was higher in SI group [mmHg (1 mmHg≈0.133 kPa): 225.57±47.85 vs. 198.32±31.59, P < 0.05], the Cdyn was higher in SI group (mL/cmH2O: 47.39±6.71 vs. 35.88±5.35, P < 0.01), the Pip was lower in SI group (mmHg: 35.85±5.77 vs. 43.87±6.68, P < 0.05). The Kaplan-Meier survival curve showed no statistically significant difference in the 28 days cumulative survival rate between the two groups (Log-Rank: χ 2 = 2.348, P = 0.125). CONCLUSIONS: The application of SI titration with PEEP in the treatment of ARDS patients may improve their prognosis.

Bacteroides ovatus alleviates high-fat and high-cholesterol -induced nonalcoholic fatty liver disease via gut-liver axis.

Gut microbiota acts as a critical regulator in the development of nonalcoholic fatty liver disease (NAFLD), making probiotics a promise therapeutic strategy. Studies are needed to identify beneficial Bacteroides strains against NAFLD. Bacteroides ovatus (B. ovatus) may also exhibit therapy effect on NAFLD. The aim of this work was to evaluate the effect of B. ovatus on NAFLD and examine the mechanism. C57BL/6 J male mice were randomly divided into three groups: a control group (NCD) that received control standard diet, a model group (M) with high-fat and high-cholesterol (HFHC) diet, and M_Bo group that was fed HFFC supplemented with B. ovatus. Treatment with B. ovatus could reduce body weight, prevent hepatic steatohepatitis and liver injury. Mechanistically, B. ovatus induced changes of gut microbial diversity and composition, characterized by a decreased Firmicutes/Bacteroidetes (F/B) ratio in M_Bo group mice, a lower abundance of Proteobacteria, Verrucomicrobiota at phylum level and Ruminococcus_torques_group, Ruminococcus_gauvreauii_group, Erysipelatoclostridium at genus level, simultaneously a remarkablely higher fecal abundance of Lachnospiraceae_NK4A136_group, norank_f__Oscillospiraceae, Colidextribacter. Compared with M group, mice treated with B. ovatus showed an markedly altered fecal short chain fatty acids (SCFAs), a decline in serum levels of lipopolysaccharide (LPS), CD163, IL-1ß, TNF-α, reduced macrophages in livers. Additionally, B. ovatus treatment caused downregulation of genes involved in denovo lipogenesis (such as Srebfl, Acaca, Scd1, Fasn), which was accompanied by the upregulation of genes related with fatty acid oxidation (such as Ppara). In conclusion, this study provides evidence that B. ovatus could ameliorate NAFLD by modulating the gut-liver axis.

Efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists for renal and cardiovascular outcomes in patients with chronic kidney disease: a meta-analysis of randomized clinical trials.

Objective: To systematically review the efficacy and safety of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in chronic kidney disease (CKD). Methods: We systematically searched six databases to identify randomized controlled trials (RCTs) about nonsteroidal MRAs for CKD, from inception to 22 August 2023. Two reviewers independently screened the retrieved articles, extracted data, and assessed the risk of bias of included RCTs using the Cochrane risk of bias tool. We then conducted meta-analysis of the data using Stata 17.0 software. Results: 11 RCTs (n = 15,817) were included in this meta-analysis. Compared with placebo, nonsteroidal MRAs significantly reduced the proportion of patients with ≥40% decline in estimated glomerular filtration rate (eGFR) from baseline [RR = 0.85, 95% CI (0.78, 0.92), p < 0.001], although the magnitude of eGFR reduction was greater [WMD = -2.83, 95% CI (-3.95, -1.72), p < 0.001]. The experimental group also had lower incidence of composite renal outcome [RR = 0.86, 95% CI (0.79, 0.93), p < 0.001] and greater reduction in urine albumin-to-creatinine ratio (UACR) from baseline [WMD = -0.41, 95% CI (-0.49, -0.32), p < 0.001], as well as reduced cardiovascular events [RR = 0.88, 95% CI (0.80, 0.95), p = 0.003]. MRAs did not increase any adverse events compared to placebo [RR = 1.00, 95% CI (0.99, 1.01), p = 0.909], but had higher incidence of hyperkalemia [RR = 2.05, 95% CI (1.85, 2.280), p < 0.001]. Compared with eplerenone, there was no significant difference in the proportion of patients with ≥40% decline in eGFR [RR = 0.57, 95% CI (0.18, 1.79), p = 0.335] or hyperkalemia [RR = 0.95, 95%CI (0.48, 1.88), p = 0.875]. Conclusion: Nonsteroidal MRAs can reduce the incidence of end-stage renal disease and cardiovascular adverse events in patients. Although there was still a risk of hyperkalemia compared to placebo, there was no significant difference in any adverse events compared to either placebo or eplerenone. It has become a new option for drug treatment of CKD patients, but more clinical trials are still needed to verify its efficacy and safety. Especially further direct comparison of the nonsteroidal MRAs to eplerenone in view of the relatively small number of patients reviewed are needed.

Recreational ball games are effective in improving social communication impairments among preschoolers diagnosed with autism spectrum disorder: a multi-arm controlled study.

BACKGROUND: This study aimed to compare the effects of two 12-week training intervention experimental ball games combined with standard behavioral rehabilitation against a control group solely utilizing standard behavioral rehabilitation on social communication impairments (SCI) in preschool children with Autism Spectrum Disorder (ASD). METHODS: A multi-arm controlled study design was implemented, involving 41 children diagnosed with ASD (mean age: 4.99 ± 0.76 years). 41 participants were randomized assigned to two experimental groups and a control group, The experimental group carried out ball combination training program group (BCTP) and mini-basketball training program group (MBTP) on the basis of routine behavioral rehabilitation, which underwent 12-week training interventions 5 times a week. The control group (n = 14) received only standard behavioral rehabilitation. Evaluations were conducted before and after interventions using the Social Responsiveness Scale, Second Edition (SRS-2). RESULTS: The results suggest that both 12-week interventions, BCTP, and MBTP, led to significant improvements in social communication impairment among children with ASD (p < 0.05). Despite enhancing the overall scores on the SRS-2, these interventions displayed varying impacts across different sub-dimensions. BCTP primarily exhibited significant enhancements in social awareness and behavior pattern (p < 0.05), whereas MBTP significantly improved social cognition and social communication (p < 0.05). Both interventions showed slight improvements in social motivation. CONCLUSIONS: The utilization of recreational ball games has showed to be effective in decreasing the impairment levels of children with ASD, while the control group experienced a worsening of outcomes. This suggests that irrespective of the specific ball game strategy employed, both can be employed on a weekly basis to complement standard behavioral rehabilitation and enhance the ability to improve the quality of life for children diagnosed with ASD. TRIAL REGISTRATION: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973;August 5, 2019).

Efficacy and safety of azilsartan medoxomil in the treatment of hypertension: a systematic review and meta-analysis.

Background: Angiotensin II receptor blockers (ARBs) are utilized for the management of hypertension and diabetes. Previous meta-analyses suggested that azilsartan medoxomil (AZL-M) improved blood pressure (BP) reduction, but there were no safety findings or suggestions for patients with hypertension or diabetes. Methods: We performed an efficacy and safety meta-analysis of randomized controlled trials (RCTs) evaluating AZL-M therapy for reducing BP in patients with hypertension. Patients with hypertension complicated by diabetes were analyzed. The relevant literature was searched in English and Chinese databases for RCTs involving AZL-M in hypertension. Efficacy variables included the change from baseline in the 24-h mean systolic/diastolic BP measured by ambulatory BP monitoring, the change from baseline in clinic systolic/diastolic BP, and responder rates. Safety variables included total adverse events (AEs), serious AEs, AEs leading to discontinuation, and AEs related to the study drug. The raw data from the included studies were utilized to calculate the odds ratio (OR) for dichotomous data and the mean difference (MD) for continuous data, accompanied by 95% confidence intervals (CIs). Statistical analysis was performed using R software. Results: A total of 11 RCTs met the inclusion criteria, representing 7,608 patients, 5 of whom had diabetes. Pooled analysis suggested a reduction in BP among patients randomized to 40 mg of AZL-M vs. control therapy [24-h ambulatory blood pressure monitoring (ABPM) mean systolic blood pressure (SBP) (MD: -2.85 mmHg), clinic SBP (MD: -3.48 mmHg), and clinic diastolic blood pressure (DBP) (MD: -1.96 mmHg)] and for 80 mg of AZL-M vs. control therapy [24-h ABPM mean SBP (MD: -3.59 mmHg), 24-h ABPM mean DBP (MD: -2.62 mmHg), clinic SBP (MD: -4.42 mmHg), clinic DBP (MD: -3.09 mmHg), and responder rate (OR: 1.46)]. There was no difference in the reduction of risks, except for dizziness (OR: 1.56) in the 80-mg AZL-M group or urinary tract infection (OR: 1.82) in the 40-mg AZL-M group. Analysis of patients with diabetes revealed that AZL-M can provide superior management, while safety and tolerability were similar to those of control therapy. Conclusions: AZL-M appears to reduce BP to a greater extent than dose-control therapy and does not increase the risk of adverse events in patients with hypertension and diabetes compared with placebo. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=464284, identifier PROSPERO CRD42023464284.