Manual Therapy for a Chronic Non-Specific Low Back Pain Rat Model.

Chronic low back pain (CLBP) is a highly prevalent condition worldwide and a major cause of disability. The majority of patients with CLBP are diagnosed with chronic non-specific low back pain (CNLBP) due to an unknown pathological cause. Manual therapy (MT) is an integral aspect of traditional Chinese medicine and is recognized as Tuina in China. It involves techniques like bone-setting and muscle relaxation manipulation. Despite its clinical efficacy in treating CNLBP, the underlying mechanisms of MT remain unclear. In animal experiments aimed at investigating these mechanisms, one of the main challenges is achieving normative MT on CNLBP model rats. Improving the stability of finger strength is a key issue in MT. To address this technical limitation, a standardized procedure for MT on CNLBP model rats is presented in this study. This procedure significantly enhances the stability of MT with the hands and alleviates common problems associated with immobilizing rats during MT. The findings of this study are of reference value for future experimental investigations of MT.

Lever positioning manipulation alters real-time brain activity in patients with lumbar disc herniation: An amplitude of low-frequency fluctuation and regional homogeneity study.

INTRODUCTION: Lumbar disk herniation (LDH) is the preeminent disease of lever positioning manipulation (LPM), a complex disorder involving alterations in brain function. Resting-state functional magnetic resonance imaging (rs-fMRI) has the advantages of non-trauma, zero radiation, and high spatial resolution, which has become an effective means to study brain science in contemporary physical therapy. Furthermore, it can better elucidate the response characteristics of the brain region of LPM intervention in LDH. We utilized two data analysis methods, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of rs-fMRI, to assess the effects of LPM on real-time brain activity in patients with LDH. METHODS: Patients with LDH (Group 1, n = 21) and age-, gender- and education-matched healthy controls without LDH (Group 2, n = 21) were prospectively enrolled. Brain fMRI was performed for Group 1 at two-time points (TPs): before LPM (TP1) and after one LPM session (TP2). The healthy controls (Group 2) did not receive LPM and underwent only one fMRI scan. Participants in Group 1 completed clinical questionnaires assessing pain and functional disorders using a Visual Analog Scale and the Japanese Orthopaedic Association (JOA), respectively. Furthermore, we employed MNL90 (Montreal Neurological Institute) as a brain-specific template. RESULTS: Compared to the healthy controls (Group 2), the patients with LDH (Group 1) had significant variation in ALFF and ReHo values in brain activity. After the LPM session (TP2), Group 1 at TP1 also showed significant variation in ALFF and ReHo values in brain activity. In addition, the latter (TP2 vs TP1) showed more significant changes in brain regions than the former (Group 1 vs Group 2). The ALFF values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The Reho values were increased in the Frontal_Mid_R and decreased in the Precentral_L in Group 1 at TP2 compared with TP1. The ALFF values were increased in the Precuneus_R and decreased in the Frontal_Mid_Orb_L in Group 1 compared with Group 2. Only three brain areas with significant activity in Group 1 compared with Group 2: Frontal_Mid_Orb_L, Frontal_Sup_Orb_L, and Frontal_Mid_R. ALFF value in the Frontal_Mid_R at TP2 correlated positively with the change rates of JOA scores between TP1 and TP2 (P = 0.04, r = 0.319, R2 = 0.102). DISCUSSION: Patients with LDH showed abnormal brain ALFF and ReHo values, which were altered after LPM. The default mode network, prefrontal cortex, and primary somatosensory cortex regions could predict real-time brain activity for sensory and emotional pain management in patients with LDH after LPM.

Bibliometric Analysis of Functional Magnetic Resonance Imaging Studies on Manual Therapy Analgesia from 2002-2022.

Background: Research on the brain mechanisms underlying manual therapy (MT)-induced analgesia has been conducted worldwide. However, no bibliometric analysis has been performed on functional magnetic resonance imaging (fMRI) studies of MT analgesia. To provide a theoretical foundation for the practical application of MT analgesia, this study examined the current incarnation, hotspots, and frontiers of fMRI-based MT analgesia research over the previous 20 years. Methods: All publications were obtained from the Science Citation Index-Expanded (SCI-E) of Web of Science Core Collection (WOSCC). We used CiteSpace 6.1.R3 to analyze publications, authors, cited authors, countries, institutions, cited journals, references, and keywords. We also evaluated keyword co-occurrences and timelines, and citation bursts. The search was conducted from 2002-2022 and was completed within one day on October 7, 2022. Results: In total, 261 articles were retrieved. The total number of annual publications showed a fluctuating but overall increasing trend. Author B. Humphreys had the highest number of publications (eight articles) and J. E. Bialosky had the highest centrality (0.45). The United States of America (USA) was the country with the most publications (84 articles), accounting for 32.18% of all publications. Output institutions were mainly the University of Zurich, University of Switzerland, and the National University of Health Sciences of the USA. The Spine (118) and the Journal of Manipulative and Physiological Therapeutics (80) were most frequently cited. The four hot topics in fMRI studies on MT analgesia were "low back pain", "magnetic resonance imaging", "spinal manipulation", and "manual therapy." The frontier topics were "clinical impacts of pain disorders" and "cutting-edge technical capabilities offered by magnetic resonance imaging". Conclusion: fMRI studies of MT analgesia have potential applications. fMRI studies of MT analgesia have linked several brain areas, with the default mode network (DMN) garnering the most attention. Future research should include international collaboration and RCTs on this topic.

A Study of Urodynamic Parameters at Different Bladder Filling Stages for Predicting Upper Urinary Tract Dilatation.

PURPOSE: To identify more accurate predictors of upper urinary tract dilatation (UUTD) in neurogenic bladder (NB) children, we studied the relationship among urodynamic parameters at different bladder filling stages, detrusor leak point pressure (DLPP) and UUTD. METHODS: A total of 158 children (3-16 years) with NB were included and then divided into 2 groups according to whether their NB diagnosis was complicated with UUTD: the UUTD group (39 patients) and those without UUTD group (control group, 119 patients). The bladder filling phase was divided into 3 equal parts: the early, middle, and end filling stages. The bladder compliance (BC) and detrusor pressure (△Pdet) at each phase and DLPP at the end filling stage were recorded. RESULTS: A BC<8 mL/cm H2O both in the middle and end stages is more specific than a BC<9 mL/cm H2O in the end stage (72%, 73%, vs. 66%), and △Pdet >8 cm H2O in the early stage, 20 cm H2O in the middle stage and 25 cm H2O in the end stage are more sensitive than △Pdet >40 cm H2O in the end stage (82%, 85%, 85%, vs. 49%). A DLPP cutoff value of 20 cm H2O showed higher sensitivity for predicting UUTD than 40 cm H2O. CONCLUSION: Low BC and a high △Pdet in the middle and end filling stages are more accurate factors than classic indicators for predicting UUTD. In addition, a DLPP value of >20 cm H2O in the end bladder filling stage shows high sensitivity.

Delayed elimination communication is a crucial factor in disposable diaper dependence in Chinese preschool-aged children.

Purpose: Elimination communication (EC) is considered to be a milestone in a child's development. Nowadays, a trend toward an older age at EC initiation has been observed globally, probably due to the convenience of disposable diaper use in daily life. The study aimed to identify potential risk factors for disposable diaper dependence (DDD) and evaluate whether an early/proper EC can reduce the risk of DDD among children in China. Methods: A cross-sectional study was performed on 13,500 children in mainland China from October 2019 to March 2020. An anonymous questionnaire was used to collect information including the sociodemographic characteristics, details about DDD and EC, and the effect of DDD on the quality of life of children. Data were analyzed by SPSS and R software. Results: The overall prevalence of DDD was 4.17% (4.31% in boys; 4.02% in girls) and decreased with age, from 8.71% at 2 years to 0.73% at 6 years (χ 2 trend = 210.392, P < 0.001). In univariable analysis, age, location or EC were associated with DDD. Four independent factors-age, location (urban), caregivers with high education levels (junior college or above) and delayed EC (after 12 months of age)-were identified to be significantly associated with DDD risk in logistic regression model. Compared with EC onset after 12 months of age, EC onset before 12 months of age was associated with a 79.6% (model 2) reduction in DDD. Four independent factors were selected to establish the nomogram for DDD based on the results of logistic regression analysis. The C-index (0.770) and the AUC (>0.7) indicated satisfactory discriminative ability of the nomogram. The calibration diagrams showed favorable consistency between the prediction of the nomogram and actual observations. Conclusion: Our findings indicate the joint contribution of age, location, caregivers' education level and EC to DDD in Chinese preschool-aged children. Timely cessation of the use of disposable diapers and early/proper EC may help to reduce the risk of DDD in children.

Prevalence, Risk Factors, and Psychological Effects of Overactive Bladder in Chinese University Students.

PURPOSE: The purpose of this study was to investigate the prevalence and risk factors of overactive bladder (OAB) in young adults and to explore the influence of OAB on mental health. METHODS: Between October 2019 and January 2020, 14,010 anonymous questionnaires were distributed to freshmen at 2 universities in Henan, China. The students came from all over the country. The questionnaire included general items and information necessary to calculate the overactive bladder symptom score, the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) score, Self-Esteem Scale (SES) score, and Self-Rating Depression Scale (SDS) score. The relationships between the prevalence of OAB and its risk factors were evaluated. RESULTS: The overall prevalence of OAB was 6.0%, with 4.3% of participants characterized as having dry OAB and 1.7% as having wet OAB. The prevalence of mild OAB was 5.5%, and that of moderate OAB was 0.5%; no severe OAB was observed. Higher prevalence rates of OAB were found among women, respondents with constipation, and respondents with primary nocturnal enuresis (PNE) (P <0.05). Compared to healthy controls, the OAB group exhibited a higher mean SDS score (52.12±8.986 vs. 47.71±9.399, P<0.001) and mean PSQI score (5.28±2.486 vs. 4.27±2.431, P<0.001), but a lower mean SES score (27.78±3.599 vs. 29.57±4.109, P<0.001). CONCLUSION: OAB significantly affects the mental health of young adults. Female sex, constipation, and PNE are risk factors for OAB.

Pharmacological inhibition of asparaginyl endopeptidase by δ-secretase inhibitor 11 mitigates Alzheimer's disease-related pathologies in a senescence-accelerated mouse model.

BACKGROUND: Currently, there is no cure for Alzheimer's disease (AD). Therapeutics that can modify the early stage of AD are urgently needed. Recent studies have shown that the pathogenesis of AD is closely regulated by an endo/lysosomal asparaginyl endopeptidase (AEP). Inhibition of AEP has been reported to prevent neural degeneration in transgenic mouse models of AD. However, more than 90% of AD cases are age-related sporadic AD rather than hereditary AD. The therapeutic efficacy of AEP inhibition in ageing-associated sporadic AD remains unknown. METHODS: The senescence-accelerated mouse prone 8 (SAMP8) was chosen as an approximate model of sporadic AD and treated with a selective AEP inhibitor,: δ-secretase inhibitor 11. Activation of AEP was determined by enzymatic activity assay. Concentration of soluble amyloid ß (Aß) in the brain was determined by ELISA. Morris water maze test was performed to assess the learning and memory-related cognitive ability. Pathological changes in the brain were explored by morphological and western blot analyses. RESULTS: The enzymatic activity of AEP in the SAMP8 mouse brain was significantly higher than that in the age-matched SAMR1 mice. The half maximal inhibitory concentration (IC50) for δ-secretase inhibitor 11 to inhibit AEP in vitro is was around 150 nM. Chronic treatment with δ-secretase inhibitor 11 markedly decreased the brain AEP activity, reduced the generation of Aß1-40/42 and ameliorated memory loss. The inhibition of AEP with this reagent not only reduced the AEP-cleaved tau fragments and tau hyperphosphorylation, but also attenuated neuroinflammation in the form of microglial activation. Moreover, treatment with δ-secretase inhibitor 11 prevented the synaptic loss and alleviated dendritic disruption in SAMP8 mouse brain. CONCLUSIONS: Pharmacological inhibition of AEP can intervene and prevent AD-like pathological progress in the model of sporadic AD. The up-regulated AEP in the brain could be a promising target for early treatment of AD. The δ-secretase inhibitor 11 can be used as a lead compound for translational development of AD treatment.

Prevalence, Risk Factors, and Psychological Effects of Primary Nocturnal Enuresis in Chinese Young Adults.

PURPOSE: This study aimed to investigate the prevalence, risk factors, and effects of primary nocturnal enuresis (PNE) on physical and mental health in young adults in mainland China. METHODS: An anonymous questionnaire was used to collect information including the sociodemographic characteristics, history of PNE, family history, daytime voiding symptoms, Pittsburgh Sleep Quality Index (PSQI) scores, Self-Esteem Scale (SES), and Self-Rating Depression Scale (SDS). A total of 22,500 university students from 23 provinces and 368 cities in mainland China were included. RESULTS: In total, 21,082 questionnaires were collected, and 20,345 of them qualified for statistical analysis. The PNE prevalence was 1.17%, and the distribution of monosymptomatic nocturnal enuresis (MNE) and nonmonosymptomatic nocturnal enuresis (NMNE) was 66.1% and 33.9%, respectively. In total, 28% of respondents with PNE reported bedwetting daily, 31.6% between 1 and 7 times weekly, and 40.4% between 1 and 4 times monthly; 80% of PNE cases had no history of treatment. The prevalence of PNE in patients with a family history, frequency, urgency, urinary incontinence, and recurrent urinary tract infections was significantly higher than in those without these conditions (P<0.001). PNE was significantly correlated with the PSQI total score (sleep quality) (P=0.011). The SES score was lower and the SDS was higher (P<0.001) in the PNE group than in those without PNE. CONCLUSION: In mainland China, the PNE prevalence among young adults was found to be high, and PNE had significant effects on physical and mental health. Risk factors included a family history, daytime voiding symptoms, and lack of treatment.

Prevalence and risk factors of overactive bladder in Chinese children: A population-based study.

AIMS: To investigate the prevalence of overactive bladder (OAB) and assess its risk factors in 5- to 14-year-old Chinese children. METHODS: A cross-sectional study of OAB prevalence was performed by distributing 11 800 anonymous self-administered questionnaires to parents in five provinces of mainland China from July to October 2018. The questionnaires included questions on sociodemographics, history of urinary tract infection (UTI), lower urinary tract symptoms (LUTS), family history of LUTS, bowel symptoms, and details about the elimination communication (EC) start time. OAB was defined as urgency and increased the daytime frequency with or without urinary incontinence. RESULTS: A total of 10 133 questionnaires qualified for statistical analysis. The overall prevalence of OAB was 9.01% and decreased with age, from 12.40% at 5 years to 4.55% at 14 years (χ2 trend = 88.899; P < .001). The proportion of dry OAB increased with age, whereas the proportion of wet OAB decreased. A late-onset of EC was associated with a high OAB prevalence (χ2 trend = 39.802; P < .001). Children with obesity, a history of UTI, nocturnal enuresis (NE), a family history of LUTS, constipation, and fecal incontinence had a higher prevalence of OAB than did normal children (P < .05). CONCLUSION: Obesity, a history of UTI, NE, a family history of LUTS, and bowel symptoms are risk factors associated with OAB. Starting EC before 12 months of age might help reduce the prevalence of OAB in children.

Blockade of the forward Na+ /Ca2+ exchanger suppresses the growth of glioblastoma cells through Ca2+ -mediated cell death.

BACKGROUND AND PURPOSE: The Na+ /Ca2+ exchanger (NCX) working in either forward or reverse mode participates in maintaining intracellular Ca2+ ([Ca2+ ]i ) homeostasis, which is essential for determining cell fate. Previously, numerous blockers targeting reverse or forward NCX have been developed and studied in ischaemic tissue injury but barely examined in glioblastoma for the purpose of anti-tumour therapy. We assessed the effect of NCX blockers on glioblastoma growth and whether NCX can become a therapeutic target. EXPERIMENTAL APPROACH: Patch-clamp recording, Ca2+ imaging, flow cytometry, and Western blot were used to study the effects of specific and non-specific NCX blockers on cultured glioblastoma cells. In vivo bioluminescent imaging was used to measure effects on grafted glioblastoma. KEY RESULTS: Selectively blocking the reverse NCX with SEA0400, SN-6, and YM-244769 did not affect tumour cell viability. Blocking the forward NCX with bepridil, CB-DMB, or KB-R7943 elevated [Ca2+ ]i and killed glioblastoma cells. Bepridil and CB-DMB caused Ca2+ -dependent cell cycle arrest together with apoptosis, which were all attenuated by a Ca2+ chelator BAPTA-AM. Systemic administration of bepridil inhibited growth of brain-grafted glioblastoma. Bepridil did not appear to have a cytotoxic effect on human astrocytes, which have higher functional expression of NCX than glioblastoma cells. CONCLUSIONS AND IMPLICATIONS: Low expression of the NCX makes glioblastoma cells sensitive to disturbance of [Ca2+ ]i . Interventions designed to block the forward NCX can cause Ca2+ -mediated injury to glioblastoma thus having therapeutic potential. Bepridil could be a lead compound for developing new anti-tumour drugs.

Disrupted Ionic Homeostasis in Ischemic Stroke and New Therapeutic Targets.

BACKGROUND: Stroke is a leading cause of long-term disability. All neuroprotectants targeting excitotoxicity have failed to become stroke medications. In order to explore and identify new therapeutic targets for stroke, we here reviewed present studies of ionic transporters and channels that are involved in ischemic brain damage. METHOD: We surveyed recent literature from animal experiments and clinical reports in the databases of PubMed and Elsevier ScienceDirect to analyze ionic mechanisms underlying ischemic cell damage and suggest promising ideas for stroke therapy. RESULTS: Dysfunction of ionic transporters and disrupted ionic homeostasis are most early changes that underlie ischemic brain injury, thus receiving sustained attention in translational stroke research. The Na+/K+-ATPase, Na+/Ca2+ Exchanger, ionotropic glutamate receptor, acid-sensing ion channels (ASICs), sulfonylurea receptor isoform 1 (SUR1)-regulated NCCa-ATP channels, and transient receptor potential (TRP) channels are critically involved in ischemia-induced cellular degenerating processes such as cytotoxic edema, excitotoxicity, necrosis, apoptosis, and autophagic cell death. Some ionic transporters/channels also act as signalosomes to regulate cell death signaling. For acute stroke treatment, glutamate-mediated excitotoxicity must be interfered within 2 hours after stroke. The SUR1-regulated NCCa-ATP channels, Na+/K+-ATPase, ASICs, and TRP channels have a much longer therapeutic window, providing new therapeutic targets for developing feasible pharmacological treatments toward acute ischemic stroke. CONCLUSION: The next generation of stroke therapy can apply a polypharmacology strategy for which drugs are designed to target multiple ion transporters/channels or their interaction with neurotoxic signaling pathways. But a successful translation of neuroprotectants relies on in-depth analyses of cell death mechanisms and suitable animal models resembling human stroke.