Neural correlates of central pain sensitization in chronic low back pain: a resting-state fMRI study.

PURPOSE: The objective of this study is to explore the neural correlates of pain sensitization in patients with chronic low back pain (cLBP). While the association between cLBP and pain sensitization has been widely reported, the underlying brain mechanism responsible for this relationship requires further investigation. METHODS: Our study included 56 cLBP patients and 56 healthy controls (HC). Functional magnetic resonance imaging data were obtained, and the voxel-wise amplitude of low-frequency fluctuation (ALFF) was calculated to identify brain alterations in cLBP patients compared to HC groups. Pearson correlation coefficients were computed to explore the association between clinical data and brain alterations. Furthermore, mediation analyses were performed to investigate the path association between brain alterations and pain-related behaviors. RESULTS: Our findings revealed that patients with cLBP exhibited higher sensitivity, attention, and catastrophizing tendencies towards pain compared to HC. Furthermore, cLBP patients displayed significantly higher ALFF in various brain regions within the "pain matrix" and the default mode network when compared to HC. The altered precuneus ALFF was positively correlated with pain intensity (R = 0.51, P<0.001) and was negatively correlated with pain sensitivity (R = -0.43, P<0.001) in cLBP patients. Importantly, the effect of altered precuneus ALFF on pain intensity was mediated by pain threshold in these patients. CONCLUSION: Our study suggests that altered neural activity in the precuneus may contribute to pain hypersensitivity, which further exacerbating pain in cLBP patients.

Therapeutic effect of autologous fascia urethral suspension on female stress urinary incontinence and analysis of risk factors affecting the efficacy.

OBJECTIVE: To observe the therapeutic effect of autologous fascial urethral suspension on female stress urinary incontinence and analyze the risk factors affecting the therapeutic effect. METHOD: The clinical data of 89 female patients with stress urinary incontinence treated in our hospital from February 2018 to February 2020 were retrospectively analyzed (training group). Another cohort of 45 patients treated in Xi'an Gaoxin Hospital from March 2020 to March 2021 were retrospectively enrolled as the validation group. Surgery-related parameters (including operation time, intraoperative blood loss, indwelling time of catheter, and hospital stay) were recorded. The scores of the urinary incontinence questionnaire short form (IC-IQ-SF), urinary incontinence quality of life questionnaire (I-QOL), and pelvic organ prolapse/urinary incontinence sexual function questionnaire (PISQ-12) were compared before and after the operation. The clinical efficacy of the treatment was counted. The risk factors affecting the treatment efficacy were analyzed. The efficacy prediction model was established by logistics regression equation and verified by the data from the validation group. RESULTS: After the treatment, the urine leakage score, urine leakage score quality of life score, and the total score were evidently reduced compared with those before the treatment (P < 0.05). Patients' I-QOL score and PISQ-12 score increased significantly after the treatment (P < 0.05). Multivariate logistics regression analysis revealed that age, BMI, history of pelvic surgery, and length of hospital stay were risk factors affecting the outcome of patients (P < 0.05). The ROC curve analysis revealed that the area under the curve of the efficacy score in predicting the treatment efficacy was 0.828, and that in the validation group was 0.895. CONCLUSION: The treatment effect of autologous fascia urethral suspension in female patients with stress urinary incontinence was significant. It improved the quality of life of patients. The risk factor analysis showed that age, BMI, history of pelvic surgery, and length of hospital stay were risk factors affecting the treatment outcome of patients.

Dynamic and Static Amplitude of Low-Frequency Fluctuation Is a Potential Biomarker for Predicting Prognosis of Degenerative Cervical Myelopathy Patients: A Preliminary Resting-State fMRI Study.

Objective: The aim of this study was to explore the clinical value of the static amplitude of low-frequency fluctuation (sALFF) and dynamic amplitude of low-frequency fluctuation (dALFF) in the identification of brain functional alterations in degenerative cervical myelopathy (DCM) patients. Methods: Voxel-wise sALFF and dALFF of 47 DCM patients and 44 healthy controls were calculated using resting-state fMRI data, and an intergroup comparison was performed. The mean of sALFF or dALFF data were extracted within the resultant clusters and the correlation analysis of these data with the clinical measures was performed. Furthermore, whole-brain-wise and region-wise multivariate pattern analyses (MVPAs) were performed to classify DCM patients and healthy controls. sALFF and dALFF were used to predict the prognosis of DCM patients. Results: The findings showed that (1) DCM patients exhibited higher sALFF within the left thalamus and putamen compared with that of the healthy controls. DCM patients also exhibited lower dALFF within bilateral postcentral gyrus compared with the healthy controls; (2) No significant correlations were observed between brain alterations and clinical measures through univariate correlation analysis; (3) sALFF (91%) and dALFF (95%) exhibited high accuracy in classifying the DCM patients and healthy controls; (4) Region-wise MVPA further revealed brain regions in which functional patterns were associated with prognosis in DCM patients. These regions were mainly located at the frontal lobe and temporal lobe. Conclusion: In summary, sALFF and dALFF can be used to accurately reveal brain functional alterations in DCM patients. Furthermore, the multivariate approach is a more sensitive method in exploring neuropathology and establishing a prognostic biomarker for DCM compared with the conventional univariate method.

Ivabradine abrogates TNF-α-induced degradation of articular cartilage matrix.

Ivabradine is most commonly used for the treatment of worsening cardiac failure in patients who cannot tolerate the maximum dose of ß-blockers or in whom treatment with ß-blockers is contraindicated. While ivabradine is regarded as a highly selective "funny current" (If) inhibitor, the molecular mechanism behind the effect of this drug remains poorly understood. In the present study, we applied ivabradine in the context of osteoarthritis by treating primary human chondrocytes with tumor necrosis factor-α (TNF-α) and measuring degradation of the articular cartilage matrix as well as the expression of various enzymes and pro-inflammatory cytokines. Our results indicate that ivabradine significantly abrogated TNF-α-induced up-regulation of matrix metalloproteinase-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5 at both the gene and protein levels. Notably, ivabradine attenuated TNF-α-induced reduction of type II collagen and aggrecan at both the mRNA and protein levels. Also, we found that ivabradine inhibited the expression and secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) as well as the production of reactive oxygen species (ROS). Mechanistically, our results indicate that ivabradine abolished the activation of nuclear factor (NF-κB) by inhibiting nuclear translocation of NF-κB p65. Knockdown of HCN2 enhanced the protective effects of ivabradine against TNF-α- induced degradation of both type II collagen and aggrecan, suggesting that the inhibitory effects of ivabradine in ECM degradation might be mediated by HCN2. Our findings demonstrate that ivabradine may indeed have a potential application in preventing excessive degradation of the articular cartilage matrix, thereby preventing the pathological development and progression of osteoarthritis.

Upregulation of the long non-coding RNA SPRY4-IT1 indicates a poor prognosis and promotes tumorigenesis in ovarian cancer.

Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. LncRNA SPRY4-IT1 serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA SPRY4-IT1 in human ovarian cancer (OC) need to be completely elucidated. The aim of the present study was to explore the lncRNA SPRY4-IT1 expression in human OC patients and its role in OC cells. We show that lncRNA SPRY4-IT1 expression is significantly upregulated in ovarian tumor tissues and OC cell lines in comparison with adjacent non-tumor control tissues and the human ovarian immortalized nontumorigenic ovarian surface epithelial (IOSE), respectively. Further analysis by Kaplan-Meier survival analysis and multivariate analysis indicated that high lncRNA SPRY4-IT1 expression may be an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in OC patients. Furthermore, the area under the receiver operating characteristic (ROC) curve of lncRNA SPRY4-IT1 was up to 0.8512, indicating lncRNA SPRY4-IT1 has diagnostic values to discriminate tumor tissues from nontumorous tissues. Also, knockdown of lncRNA SPRY4-IT1 inhibited the proliferation of OC cells by CCK-8 assay and clonogenic assay and arrested cell cycle at a G0/G1 stage in OC cells. In conclusion, these results suggest that lncRNA SPRY4-IT1 may be considered as a new predictor in the clinical prognosis of OC patients.