Expression of insulin-like growth factor binding protein 5 in the vaginal wall tissues of older women with pelvic organ prolapse.

This study aimed to investigate the expression and significance of insulin-like growth factor binding protein 5 (IGFBP5) and extracellular matrix (ECM) related proteins in anterior vaginal wall tissues among aged pelvic organ prolapse (POP) patients. Tissues from the anterior vaginal wall were collected from 28 patients with POP and 20 patients without POP. The expression of protein and mRNA levels of IGFBP5 and ECM related proteins were evaluated in the vaginal wall tissues using immunohistochemistry, western blotting, and RT-qPCR techniques. The expression levels were then compared with clinical parameters. The expression levels of protein and mRNA of IGFBP5, collagen I, and collagen III were significantly lower in the POP group. Protein and mRNA expression levels of MMP2 were significantly higher in the POP group. IGFBP5 protein and mRNA expression levels were negatively correlated with age and significantly lower in older POP patients (≥ 65 years old) compared to younger POP patients (< 65 years old). IGFBP5 protein and mRNA expression levels were also significantly lower in POP-Q stage IV patients compared to POP-Q stage III patients. IGFBP5 expression level is negatively correlated with the age and severity of prolapse. The significant decrease in IGFBP5 expression may play a crucial part in the aging process and the occurrence of POP.

Intermittent theta-burst stimulation combined with physical therapy as an optimal rehabilitation in Parkinson's disease: study protocol for a randomised, double-blind, controlled trial.

BACKGROUND: First-line rehabilitative strategies to improve motor deficits are based on functional training (physical or occupational therapy), which has been demonstrated to facilitate neural reorganisation. Accumulating evidence suggests that non-invasive brain stimulation techniques, such as repetitive TMS (rTMS), may enhance neuroplasticity, thereby facilitating neural reorganisation and recovery from Parkinson's disease. Evidence also shows that intermittent theta-burst stimulation (iTBS) can improve motor function and quality of life in patients by promoting the excitability and neural remodelling of cerebral cortex. We aimed to combine iTBS stimulation with physiotherapy to improve the rehabilitation effect compared to physiotherapy alone in patients with Parkinson's disease. METHODS: This randomised, double-blind clinical trial will enrol 50 Parkinson's disease patients aged 45-70 years with Hoehn and Yahr scale scores of 1-3. Patients are randomly assigned to either the iTBS + physiotherapy or sham-iTBS + physiotherapy group. The trial consists of a 2-week double-blind treatment period and a 24-week follow-up period. iTBS and sham-iTBS will be administered twice daily for 10 days based on physiotherapy. The primary outcome will be the third part of Movement Disorders-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) from the baseline to the first 2 days following completion hospitalised intervention. The secondary outcome will be 39-item Parkinson's Disease Questionnaire (PDQ-39) at 4 weeks, 12 weeks and 24 weeks after intervention. Tertiary outcomes are clinical evaluations and mechanism study outcomes such as NMSS, 6MWD, 10MT, TUG, BBS, MRI, and EEG, the length of time between the drug needs to be adjusted when symptoms fluctuate. DISCUSSION: The aim of this study is to demonstrate that iTBS can promote overall function and quality of life in Parkinson's disease patients using physiotherapy and that this efficacy may be associated with altered neuroplasticity in exercise-related brain regions. The iTBS combined with physiotherapy training model will be evaluated during a 6-month follow-up period. With significant improvement in quality of life and motor function, iTBS combined with physiotherapy can be considered as a first-line rehabilitation option for Parkinson's disease. The potential of iTBS to enhance neuroplasticity in the brain should have a more positive impact in increasing the generality and efficiency of physiotherapy, improving the quality of life and overall functional status of patients with Parkinson's disease. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200056581. Registered on 8 February 2022.

Circular RNAs in Parkinson's Disease: Reliable Biological Markers and Targets for Rehabilitation.

In clinical practice, the underlying pathogenesis of Parkinson's disease (PD) remains unknown. Circular RNAs (circRNAs) have good biological properties and can be used as biological marker. Rehabilitation as a third treatment alongside drug and surgery has been shown to be clinically effective, but biomarkers of rehabilitation efficiency at genetic level is still lacking. In this study, we identified differentially expressed circRNAs in peripheral blood exosomes between PD patients and health controls (HCs) and determined whether these circRNAs changed after rehabilitation, to explore the competing RNA networks and epigenetic mechanisms affected. We found that there were 558 upregulated and 609 downregulated circRNAs in PD patients compared to HCs, 3398 upregulated and 479 downregulated circRNAs in PD patients after rehabilitation compared to them before rehabilitation, along with 3721 upregulated and 635 downregulated circRNAs in PD patients after rehabilitation compared to HCs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially expressed circRNAs may affect the stability of the cellular actin backbone and synaptic structure by influencing the aggregation of α-synuclein (a-syn). We selected two circRNAs overexpressed in PD patients for validation (hsa_circ_0001535 and hsa_circ_0000437); the results revealed that their expression levels were all reduced to varying degrees (p < 0.05) after rehabilitation. After network analysis, we believe that hsa_circ_0001535 may be related to the aggregation of a-syn, while hsa_circ_0000437 may act on hsa-let-7b-5p or hsa-let-7c-5p through sponge effect to cause inflammatory response. Our findings suggest that rehabilitation can mitigate the pathological process of PD by epigenetic means.

Blind box over-engagement and suicide risk among adolescents and young adults: Results of a large-scale survey.

Background: Gambling appears to be an independent risk factor for suicide among the young population worldwide. Blind boxes are collectable toys packed randomly in the box, which share certain similarities with gambling and are popular among the young population. This is the first study that examined the association between blind box engagement and suicide risk in the young population, the leading consumption group of blind boxes. Methods: This study is part of a large-scale, cross-sectional study using convenience sampling conducted Oct 26 to Nov 18, 2021, which covered all the university and college students in the Jilin province, China. A total of 73,206 participants completed the survey with valid data for the current study (male: N = 28,762; female: N = 44,444; Mean age = 19·59). Participants' blind box engagement, suicide risk, depression, anxiety, alcohol use, smoking habit, and sociodemographic characteristics were assessed. First, we used univariate and multivariable binary logistic regression models to examine the relationship between blind box engagement and suicide risk in all participants. Second, we tested whether depression and anxiety would mediate the association between blind box engagement and suicide risk. Third, we analysed the association between "Frequency (i.e., frequency of blind box engagement)," "Bet (i.e., expenditure on the blind box that exceeds affordability)," "Tolerance (i.e., level of addiction)," "Borrowed (i.e., the amount of money borrowed for blind box engagement)," and suicide risk in the group with blind box engagement history. Findings: 4,195 participants (5·73%) have engaged in blind boxes, with 3,255 females (77·59%) and 940 males (22·41%). In the univariate models, binary logistic regression showed that blind box engagement was associated with suicide risk in both male and female participants (male: OR = 2·21, 95% CI = 1·86-2·63; female: OR = 1·64, 95% CI = 1·50-1·78). In the multivariable models, after controlling age, subjective socioeconomic status, per capita disposable income, alcohol use, and smoking habit, blind box engagement still was associated with suicide risk across genders (male: OR = 2·25, 95% CI = 1·89-2·68; female: OR = 1·58, 95% CI = 1·45-1·73). Depression (male: indirect effect = 0·31, SE = 0·04, p < 0·001; female: indirect effect = 0·20, SE = 0·02, p < 0·001) and anxiety (male: indirect effect = 0·26, SE = 0·03, p < 0·001; female: indirect effect = 0·13, SE = 0·02, p < 0·001) mediate the association between blind box engagement and suicide risk. Within the blind box engagement group, forward binary logistic regression revealed that "Tolerance" was associated with participants' suicide risk in both males (p = 0·001) and females (p < 0·001); "Borrowed" (p = 0·019) alone was associated with the male participants' suicide risk. Interpretation: Our findings showed that blind box over-engagement is positively associated with suicide risk in both young males and females, and this association persisted after adjusting for influencing factors. In spite of the limitations in this study (e.g., cross-sectional, convenience sampling), current findings can assist policymakers in developing regulations for such a prosperous youth-dominant consumption industry while protecting youth's mental health worldwide. Funding: None.