Finite Element Analysis of Pelvic Floor Biomechanical Models to Elucidate the Mechanism for Improving Urination and Defecation Dysfunction in Older Adults: Protocol for a Model Development and Validation Study.

BACKGROUND: The population is constantly aging, and most older adults will experience many potential physiological changes as they age, leading to functional decline. Urinary and bowel dysfunction is the most common obstacle in older people. At present, the analysis of pelvic floor histological changes related to aging has not been fully elucidated, and the mechanism of improving intestinal control ability in older people is still unclear. OBJECTIVE: The purpose of this study is to describe how the finite element method will be used to understand the mechanical characteristics of and physiological changes in the pelvic cavity during the rehabilitation process, providing theoretical support for the mechanism for improving urination and defecation dysfunction in older individuals. METHODS: We will collect magnetic resonance imaging (MRI) and computed tomography (CT) data of the pelvic cavity of one male and one female volunteer older than 60 years and use the finite element method to construct a 3D computer simulation model of the pelvic cavity. By simulating different physiological states, such as the Valsalva maneuver and bowel movement, we will verify the accuracy of the constructed model, investigate the effects of different neuromuscular functional changes, and quantify the impact proportions of the pelvic floor muscle group, core muscle group, and sacral nerve. RESULTS: At present, we have registered the study in the Chinese Clinical Trial Registry and collected MRI and CT data for an older male and an older female patient. Next, the construction and analysis of the finite element model will be accomplished according to the study plan. We expect to complete the construction and analysis of the finite element model by July 2024 and publish the research results by October 2025. CONCLUSIONS: Our study will build finite element models of the pelvic floor of older men and older women, and we shall elucidate the relationship between the muscles of the pelvic floor, back, abdomen, and hips and the ability of older adults to control bowel movements. The results of this study will provide theoretical support for elucidating the mechanism for improving urination and defecation dysfunction through rehabilitation. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400080749; https://www.chictr.org.cn/showproj.html?proj=193428. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56333.

Triphenyl phosphate induced apoptosis of mice testicular Leydig cells and TM3 cells through ROS-mediated mitochondrial fusion inhibition.

Triphenyl phosphate (TPHP) is a widely used organophosphate flame retardant and has biological toxicity. Previous studies showed TPHP can restrain testosterone biosynthesis in Leydig cells, while the underlying mechanisms remain unclear. In this study, C57BL/6J male mice were exposed to 0, 5, 50, and 200 mg/kg B.W. of TPHP for 30 d by oral, as well as TM3 cells were treated with 0, 50, 100, and 200 µM of TPHP for 24 h. Results showed that TPHP induced testes damage, including spermatogenesis disorders and testosterone synthesis inhibition. Meanwhile, TPHP can cause apoptosis in testicular Leydig cells and TM3 cells, as evidenced by the increased apoptosis rate and decreased Bcl-2/Bax ratio. Moreover, TPHP disrupted mitochondrial ultrastructure of testicular Leydig cells and TM3 cells, reduced healthy mitochondria content and depressed mitochondrial membrane potential of TM3 cells, as well as inhibited mitochondrial fusion proteins mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and optic atrophy 1 (Opa1) expression, without effect on mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission 1 (Fis1) in testicular tissue and/or TM3 cells. Then, the mitochondrial fusion promoter M1 was used to pre-treat TPHP-exposed TM3 cells to determine the roles of mitochondrial fusion inhibition in TPHP-induced Leydig cells apoptosis. The results showed M1 pretreatment alleviated the above changes and further mitigated TM3 cells apoptosis and testosterone levels decreased, indicating TPHP induced TM3 cells apoptosis by inhibited mitochondrial fusion. Intriguingly, the intervention experiment of N-acetylcysteine (NAC) showed that TPHP-induced mitochondrial fusion inhibition is ROS dependent, because inhibition of ROS overproduction alleviated mitochondrial fusion inhibition, and subsequently relieved TPHP-induced apoptosis in TM3 cells. In summary, above data revealed that apoptosis is a specific mechanism for TPHP-induced male reproductive toxicity, and that ROS-mediated mitochondrial fusion inhibition is responsible for Leydig cells apoptosis caused by TPHP.

Comparison of Two Different Threshold Values for the Measurement of Gastric Residual Volume on Enteral Nutrition Support in the Neurocritically Ill Patients.

Background: Although recommendations on gastric residual volume (GRV) have been applied to the clinical practice of patients who are intubated, evidence-based data about the GRV of patients who are neurocritically ill are still lacking. We conducted this study to investigate the safety of increased GRV in patients who are neurocritically ill on enteral nutrition (EN) support. Methods: Patients who are neurocritically ill feeding through intragastric enteral tubes were recruited consecutively between July 2018 and June 2021. Patients were divided into a control group (GRV 100 ml) and a study group (GRV 200 ml). Demographic data, admission diagnosis, and severity scores were collected from the patient medical records. The frequency of diet volume ratio (diet received/diet prescribed), the incidence of gastrointestinal complications, and outcome variables were evaluated. Results: There were 344 patients enrolled, of whom 197 had mechanical ventilation support. High GRV events in the control group were more frequent than those in the study group (38.1 vs. 22.8%, p = 0.002). The total gastrointestinal complication rate did not differ significantly between the two groups (study group: 61.1%, 102/167 vs. control group: 67.9%, 114/168). In the study group, two patients had aspiration (1.2 vs. 0%, p = 0.245). The study group showed a superior diet volume ratio, but the difference was not significant. The outcomes of the study group were slightly better than those of the control group; however, no significant differences were observed between the two groups concerning the length of stay in the neurointensive care unit (19.5 days vs. 25.3 days) and mortality (10.8 vs. 14.9%) at discharge. Conclusion: Our results suggest that 200 ml may be a safe normal limit for GRV in patients who are neurocritically ill.