The effect and safety of obeticholic acid for patients with nonalcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) is one of the primary causes of chronic liver disease worldwide. Obeticholic acid (OCA), a potent farnesoid X nuclear receptor activator, has shown promise for treating NASH-related fibrosis due to its anti-fibrotic effects. This study aimed to examine the efficacy of OCA for patients with NASH as well as to investigate its impact on dyslipidemia. METHOD: A search of databases including PubMed, Embase, and Cochrane Library from January 1, 2010, to November 1, 2022, was conducted to identify systematic reviews of randomized controlled trials involving NASH patients. Inclusion criteria comprised randomized controlled trials that specifically addressed NASH as diagnosed through magnetic resonance imaging, computed tomography, or histology. The results were then categorized, with consideration given to both biochemical and histological outcomes. RESULT: Five NASH studies were ultimately selected for further analysis. In terms of biochemical indicators, patients receiving OCA treatment showed improvements in alanine transaminase (mean difference: -19.48, 95% confidence interval [CI]: -24.39 to 14.58; P < .05) and aspartate aminotransferase (mean difference: -9.22, 95% CI: -12.70 to 5.74; P < .05). As for histological improvement, OCA treatment reduced fibrosis (odds ratio [OR]: 1.95, 95% CI: 1.47-2.59; P = .001) and steatosis (OR: 1.95, 95% CI: 1.47-2.59; P = .001). No significant differences were observed regarding adverse events (1.44, 95% CI: 0.57-3.62; P > .001). Regarding dyslipidemia, mean differences between total cholesterol and low-density lipoprotein were found to be high (0.33, 95% CI: 0.01-0.64, P < .05; 0.39, 95% CI: 0.04-0.73, P < .05). In the case of pruritus, OCA achieved a high OR (3.22, 95% CI: 2.22-4.74) compared with placebo. CONCLUSION: OCA also reduced several liver test markers compared to placebo, including the biochemical indicators alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase, and improved hepatocellular ballooning, fibrosis, steatosis, and lobular inflammation. Although the incidence of adverse events did not significantly differ between OCA and placebo groups among NASH patients, OCA treatment was found to elevate total cholesterol and low-density lipoprotein levels, and the reported severity of pruritus increased with higher doses of OCA.

Design and motion control of exoskeleton robot for paralyzed lower limb rehabilitation.

Introduction: Patients suffering from limb movement disorders require more complete rehabilitation treatment, and there is a huge demand for rehabilitation exoskeleton robots. Flexible and reliable motion control of exoskeleton robots is very important for patient rehabilitation. Methods: This paper proposes a novel exoskeleton robotic system for lower limb rehabilitation. The designed lower limb rehabilitation exoskeleton robot mechanism is mainly composed of the hip joint mechanism, the knee joint mechanism and the ankle joint mechanism. The forces and motion of the exoskeleton robot were analyzed in detail to determine its design parameters. The robot control system was developed to implement closed-loop position control and trajectory planning control of each joint mechanism. Results: Multiple experiments and tests were carried out to verify robot's performance and practicality. In the robot angular response experiments, the joint mechanism could quickly adjust to different desired angles, including 15°, 30°, 45°, and 60°. In the trajectory tracking experiments, the exoskeleton robot could complete tracking movements of typical actions such as walking, standing up, sitting down, go upstairs and go downstairs, with a maximum tracking error of ±5°. Robotic wearing tests on normal people were performed to verify the assistive effects of the lower limb rehabilitation exoskeleton at different stages. Discussion: The experimental results indicated that the exoskeleton robot has excellent reliability and practicality. The application of this exoskeleton robotic system will help paralyzed patients perform some daily movements and sports.

Association of the oxidative balance score with obesity and body composition among young and middle-aged adults.

Objective: The oxidative balance score (OBS) is important for determining the cause of obesity and its complications. We aimed to evaluate the association between OBS and obesity and other segmental body composition parameters among young and middle-aged U.S. adults. Methods: 9,998 participants from the National Health and Nutrition Examination Survey 2011-2018 were included. Lean mass percentage (LM%) and FM% were evaluated by dual-energy x-ray absorptiometry. Obesity was defined as body FM% ≥25% in men and ≥ 35% in women. The OBS was scored by 5 pro-oxidant and 21 antioxidant factors. Associations of quartiles of OBS with obesity risk were estimated using multivariable logistic regression models. Multivariable linear regression was conducted to estimate the association between OBS and segmental body composition measures including the arm LM%, leg LM%, torso LM%, whole LM%, arm FM%, leg FM%, torso FM% and total FM%. Results: Compared to participants in the lowest quartile of OBS, those in the highest quartile of OBS were associated with a lower risk of BMI-defined obesity BMI-defined obesity [0.43 (0.36, 0.50)] and FM%-related obesity [0.43 (0.35, 0.52)]. Additionally, OBS was negatively associated with FM% of the limb and torso but positively associated with the percentage of lean mass (LM%) of the limb and trunk. Conclusion: OBS was negatively associated with the risk of obesity and segmental FM%, but was positively associated with segmental LM% among US adults, indicating that adhering to an anti-oxidative diet and lifestyle management may be beneficial for preventing segmental obesity.

Predictive Accuracy Analysis of a Novel Robotic-Assisted System for Total Knee Arthroplasty:A Prospective Observational Study.

Background: Robotic-assisted total knee arthroplasty (RATKA) has been reported to enhance operative decision-making. The purpose of this study was intended to assess the predictive accuracy of bone cuts, lower limb alignment, and component size of a novel system for RATKA preoperatively and intraoperatively. Methods: Preoperatively planned bone cuts, limb alignment, and component size were projected using a reconstructed 3D model. Intraoperative bone cuts and postoperative limb alignment were measured. Errors between planned and real bone cuts, limb alignment, and component size were compared. Results: The mean absolute errors for bone cuts and alignment were within 1.40mm/1.30° with a standard deviation (SD) of 0.96mm/1.12°. For all errors of bone cuts and alignment compared with the plan, there were no statistically significant differences except for the lateral distal of femoral cuts (P=0.004). The accuracy for predicting the femoral, tibial, and polyethylene component sizes was 100% (48/48), 90% (43/48), and 88% (42/48), respectively. Regarding all mean absolute errors of bone cuts and alignments, no significant differences were observed among surgeons. Conclusion: The novel robotically-assisted system for RATKA donated reliable operative decision-making based on the predictive accuracy regardless of the surgeon's level of experience.

Impacts of cadmium accumulation on the diversity, assembly processes, and co-occurrence patterns of archaeal communities in marine sediments.

There is limited understanding regarding the changes in the ecological processes and the mechanisms of archaeal community in response to heavy metal contamination in the marine sediments. In this study, sediment samples were collected from 46 locations near harbors, and the concentration of heavy metals and the diversity of archaeal communities were investigated to understand the impact of Cd on archaeal communities. The results demonstrated a significant correlation between the diversity of archaeal community and Cd concentration, particularly showing a linear decrease in the species richness with rising Cd concentration. ANME-1b was identified as a significantly enriched archaeal taxon in the higher Cd environment. Null model and neutral community model indicated that the ecological assembly of archaeal communities in marine sediments was primarily governed by the stochastic processes, with dispersal limitation being the primary factor. The contribution of deterministic process to the assembly of archaeal communities in higher Cd environments increased clearly, accompanied by a notable reduction in species migration rates and widths of ecological niche of archaeal populations. Co-occurrence network analysis revealed an obvious increase in species interactions in higher Cd environments, with an apparent rise in the proportion of competitive relationships and an increase in the number of keystone species. Moreover, archaeal species formed a more complex and stable community to cope with Cd stress. This study provides new insights into the impacts of heavy metals on the ecological processes of marine microorganisms and the underlying mechanisms.

Rhizoma Alismatis Decoction improved mitochondrial dysfunction to alleviate SASP by enhancing autophagy flux and apoptosis in hyperlipidemia acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas, especially hyperlipidemia acute pancreatitis (HLAP) is the third leading cause of acute pancreatitis which is more severe with a greater incidence of persistent multiorgan failure. HLAP inflicts injury upon the organelles within the acinar cell, particularly mitochondria, the endolysosomal-autophagy system, and is accompanied by senescence-associated secretory phenotype (SASP). RAD, only two consists of Rhizoma Alismatis and Atractylodes macrocephala Rhizoma, which is best known for its ability to anti-inflammatory and lipid-lowering. Nevertheless, the mechanism by which RAD alleviates HLAP remains obscure, necessitating further investigation. PURPOSE: The study aimed to assess the effects of the RAD on HLAP and to elucidate the underlying mechanism in vivo and in vitro, offering a potential medicine for clinical treatment for HLAP. STUDY DESIGN AND METHODS: C57BL/6 mice with hyperlipidemia acute pancreatitis were induced by HFD and CER, then administrated with RAD. AR42J were stimulated by cerulein or conditioned medium and then cultured with RAD. Serums were analyzed to evaluate potential pancreas and liver damage. Furthermore, tissue samples were obtained for histological, and protein investigations by H&E, Oil red staining, and Western blot. In addition, western blot and immunofluorescent staining were utilized to estimate the effect of RAD on mitochondrial function, autophagy flux, and SASP. RESULTS: In vivo, RAD considerably alleviated systemic inflammation while attenuating TC, TG, AMY, LPS, inflammatory cytokines, histopathology changes, oxidative damage, mitochondrial fission, and autophagy markers in HLAP mice. Impaired autophagy flux and mitochondrial dysfunction resulted in a significant enhancement of NLRP3 and IL-1ß in the pancreas. RAD could reverse these changes. In vitro, RAD significantly restored mitochondrial membrane potential and oxidative phosphorylation levels. RAD decreased Beclin-1 and LC3-II expression and increased LAMP-1 and Parkin-Pink expression, which showed that RAD significantly ameliorated HLAP-induced damage to the mitochondria function by suppressing mitochondrial oxidative damage and enhancing autophagy flux and mitophagy to remove the damaged mitochondria. In addition, we found that RAD could up-regulate the expression of BAX, and Bad and down-regulate the expression of p16, and p21, indicating that RAD could promote damaged cell apoptosis and alleviate SASP. CONCLUSIONS: This study revealed that RAD ameliorates mitochondrial function to alleviate SASP through enhancing autophagy flux, mitophagy, and apoptosis which provided a molecular basis for the advancement and development of protection strategies against HLAP.

Intraspecific diploidization of a halophyte root fungus drives heterosis.

How organisms respond to environmental stress is a key topic in evolutionary biology. This study focused on the genomic evolution of Laburnicola rhizohalophila, a dark-septate endophytic fungus from roots of a halophyte. Chromosome-level assemblies were generated from five representative isolates from structured subpopulations. The data revealed significant genomic plasticity resulting from chromosomal polymorphisms created by fusion and fission events, known as dysploidy. Analyses of genomic features, phylogenomics, and macrosynteny have provided clear evidence for the origin of intraspecific diploid-like hybrids. Notably, one diploid phenotype stood out as an outlier and exhibited a conditional fitness advantage when exposed to a range of abiotic stresses compared with its parents. By comparing the gene expression patterns in each hybrid parent triad under the four growth conditions, the mechanisms underlying growth vigor were corroborated through an analysis of transgressively upregulated genes enriched in membrane glycerolipid biosynthesis and transmembrane transporter activity. In vitro assays suggested increased membrane integrity and lipid accumulation, as well as decreased malondialdehyde production under optimal salt conditions (0.3 M NaCl) in the hybrid. These attributes have been implicated in salinity tolerance. This study supports the notion that hybridization-induced genome doubling leads to the emergence of phenotypic innovations in an extremophilic endophyte.

Association between oxidative stress exposure and colorectal cancer risk in 98,395 participants: results from a prospective study.

Background: The intricate role of oxidative stress (OS) in colorectal cancer (CRC) initiation is underscored by an imbalance between pro-oxidants and antioxidants. Utilizing the Oxidative Balance Score (OBS) as a metric, this study aims to investigate the association between OS exposure and CRC risk, while also examining potential sex-specific differences in a large U.S. cohort. Methods: The study included 98,395 adults from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. To construct the OBS, 14 dietary and lifestyle factors intricately associated with oxidative stress were quantified. A higher OBS value indicated a more favorable oxidative balance pattern or diminished OS exposure. Due to sex-specific differences in OBS, associations were evaluated separately for men and women based on Cox regression analysis. Subgroup analyses were conducted to elucidate potential modifiers. Results: During 867,963.4 person-years of follow-up, 1,054 CRCs occurred. The mean (SD) age and OBS were 65.52 (5.73) years and 14.09 (3.95) points, respectively. In the fully adjusted Cox model, we observed an inverse association between OBS and CRC incidence in women (HRQ5vsQ1: 0.72; 95% CI: 0.52, 0.99; P for trend = 0.018) but not men. Subgroup analyses revealed the inverse association was more pronounced among women without versus with a family history of CRC (HRQ5 vsQ1: 0.66, 95% CI: 0.47-0.93; P for trend = 0.001; P for interaction = 0.001). The results remained robust after several sensitivity analyses. Conclusion: Higher OBS was associated with lower CRC risk in women but not men; this inverse association was stronger among women without a family history of CRC. These findings suggest exposure to OS may confer sex-specific CRC risk effects, especially for women without a family history of CRC.