Effects of exercise therapy on disability, mobility, and quality of life in the elderly with chronic low back pain: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Exercise is an effective treatment in chronic low back pain (CLBP), but there are few studies on CLBP in the elderly, and the intervention effect is controversial. We aimed to compare the efficacy of different exercises therapy on CLBP, dysfunction, quality of life, and mobility in the elderly. METHODS: We searched Web of Science, MEDLINE, Cochrane Library, Chinese National Knowledge Infrastructure, EMBASE, and PubMed from the database inception till December 31, 2022. The publication languages were Chinese and English. Randomized controlled trials (RCTs) of exercise intervention in the elderly (≥ 60 years) with CLBP were included. Two reviewers independently extracted the data and evaluated them using the Revised Cochrane Risk of Bias Tool for Randomized Trials 2 (RoB2). The pooled effect sizes on different aspects of outcome measures were calculated. RESULTS: Sixteen articles (18 RCTs) were included, comprising a total of 989 participants. The quality of included studies was relatively high. Meta-analysis results indicated that exercise therapy could improve visual analog scale (VAS) (WMD = - 1.75, 95% CI - 2.59, - 0.92, p < 0.05), Oswestry disability index (ODI) (WMD = - 9.42, 95% CI - 15.04, - 3.79, p < 0,005), short-form 36-item health survey physical composite summary (SF-36PCS) (WMD = 7.07, 95% CI 1.01, 13.14, p < 0.05), short-form 36-item health survey mental composite summary (SF-36MCS) (WMD = 7.88, 95% CI 0.09, 15.67, p < 0.05), and timed up and go test (TUG) (WMD = - 0.92, 95% CI - 2.22, 0.38, p < 0.005). CONCLUSION: Exercise therapy effectively improved VAS, ODI, and SF-36 indexes in the elderly. Based on the subgroup, when designing the exercise therapy regimen, aerobics, strength, and mind-body exercise (≥ 12 weeks, ≥ 3 times/week, ≥ 60 min) should be considered carefully, to ensure the safety and effectiveness for the rehabilitation of CLBP patients. More high-quality trials are needed in future to confirm the effect of exercise on SF-36 and TUG indexes.

The Association of Blood Urea Nitrogen to Creatinine Ratio and the Prognosis of Critically Ill Patients with Cerebral Infarction: A Cohort Study.

Background: To evaluate the association between blood urea nitrogen (BUN) to creatinine (Cr) (BUN/Cr) ratio and the in-hospital mortality of critically ill patients with cerebral infarction in intensive care unit (ICU). Methods: In this cohort study, the data of 3059 participants with cerebral infarction were collected from the Medical Information Mart for Intensive Care (MIMIC)-III and the MIMIC-IV database. After propensity score matching (PSM) on age and gender, 2085 people were involved in and divided into the alive group (n = 1390) and the dead group (n = 695) based on the results of follow-up. Multivariate logistic analyses were applied to identify the confounders and the association between BUN/Cr and mortality of cerebral infarction. Results: The median follow-up time was 10.5 days. Among 2778 participants, 695 were dead at the end of follow-up. Univariate analysis revealed that BUN/Cr [risk ratio (RR) = 1.01, 95% confidence interval (CI): 1.01-1.02] might be associated with the in-hospital mortality of cerebral infarction patients. After adjusting for respiratory failure, malignant cancer, anticoagulation, liver disease, white blood cell (WBC), red cell distribution width (RDW), glucose, bicarbonate, and temperature, BUN/Cr had week correlation with the increased risk of in-hospital mortality of cerebral infarction patients (RR = 1.01, 95% CI: 1.01-1.02). Conclusion: This study evaluated the association between BUN/Cr and the in-hospital mortality of cerebral infarction patients in ICU and found that BUN/Cr had weak correlation with the increased risk of in-hospital mortality of patients with cerebral infarction in ICU especially in males and those with respiratory failure, malignant cancer, and without liver disease, as well as those receiving anticoagulation.

Mitochondrial Dysfunction in Oxidative Stress-Mediated Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is the most common contributor to low back pain (LBP). Recent studies have found that oxidative stress and reactive oxygen species (ROS) play an important role in IVDD. As a by-product of aerobic respiration, ROS is mainly produced in the mitochondria by the electron transport chain and other mitochondrial located proteins. With the excessive accumulation of ROS, mitochondria are also the primary target of ROS attack in disc cells. A disrupted balance between intracellular ROS production and antioxidant capacity will lead to oxidative stress, which is the key contributor to cell apoptosis, cell senescence, excessive autophagy, and mitochondrial dysfunction. As the pivotal ingredient of oxidative stress, mitochondrial dysfunction manifests as imbalanced mitochondrial dynamics and dysregulated mitophagy. Mitochondria can alter their own dynamics through the process of fusion and fission, so that disabled mitochondria can be separated from the mitochondrial pool. Moreover, mitophagy participates by clearing these dysfunctional mitochondria. Abnormality in any of these processes either increases the production or decreases the clearance of ROS, leading to a vicious cycle that results in the death of intervertebral disc cells in large quantities, combined with degradation of the extracellular matrix and overproduction of matrix metalloproteinase. In this review, we explain the changes in mitochondrial morphology and function during oxidative stress-mediated IVDD and highlight the important role of mitochondria in this process. Eventually, we summarize the IVDD therapeutic strategies targeting mitochondrial dysfunction based on current understanding of the role of oxidative stress in IVDD.

LncRNA NEAT1 alleviates ischemic stroke via transcriptional inhibition of NLRP3 mediated by the miR­10b­5p/BCL6 axis.

Cerebral ischemic stroke (CIS) is a significant cause of disability and death. Inflammation usually occurs after CIS and accelerates cellular damage. NLRP3 plays a key role in the formation of CIS­associated inflammasome. Understanding how NLRP3 is regulated bears great importance. We hypothesized that lncRNA NEAT1 can downregulate NLRP3 expression by regulating the miR­10b­5p/BCL6 axis, and thus regulate microglia­driven inflammation. The expression of NEAT1 was analyzed in CIS patients and an in vitro model of oxygen and glucose deprivation/re­oxygenation (OGD/R). We assessed the levels of pro­inflammatory cytokines IL­18 and IL­1ß with ELISA. Interactions between NEAT1/miR­10b­5p and miR­10b­5p/BCL6 were determined by luciferase assay. The interaction of BCL6 and NLRP3 was identified by ChIP; RNA, and protein levels were evaluated by qRT­PCR and western blot, respectively. We found that NEAT1 level was decreased in CIS patients and OGD/R treated cells. OGD/R exerted pro­inflammasome effects by increasing the expression of inflammasome­associated proteins and ROS and malondialdehyde (MDA) while inhibiting SOD production. This effect was partially antagonized by NEAT1. We bioinformatically identified interactions between NEAT1/miR­10b­5p, BCL6/miR­10b­5p, and NLRP3­promoter/BCL6, and validated them by luciferase assay, qRT­PCR, and ChIP. NEAT1 inhibited miR­10b­5p and upregulated BCL6 by ceRNA mechanism and alleviated OGD/R induced cell damage. We also proved that BCL6 was a repressive transcription factor in the regulation of NLRP3 expression. Thus, lncRNA NEAT1 inhibited inflammasome activation by NLRP3 in microglia via the NEAT1/ miR­10b­5p/BCL6/NLRP3 regulatory axis, which alleviated deleterious outcomes of ischemic stroke.

Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination.

Bone health requires adequate bone mass, which is maintained by a critical balance between bone resorption and formation. In our study, we identified beraprost as a pivotal regulator of bone formation and resorption. The administration of beraprost promoted differentiation of mouse bone mesenchymal stem cells (M-BMSCs) through the PI3K-AKT pathway. In co-culture, osteoblasts stimulated with beraprost inhibited osteoclastogenesis in a rankl-dependent manner. Bone mass of p53 knockout mice remained stable, regardless of the administration of beraprost, indicating that p53 plays a vital role in the bone mass regulation by beraprost. Mechanistic in vitro studies showed that p53 binds to the promoter region of neuronal precursor cell-expressed developmentally downregulated 4 (Nedd4) to promote its transcription. As a ubiquitinating enzyme, Nedd4 binds to runt-related transcription factor 2 (Runx2), which results in its ubiquitination and subsequent degradation. These data indicate that the p53-Nedd4-Runx2 axis is an effective regulator of bone formation and highlight the potential of beraprost as a therapeutic drug for postmenopausal osteoporosis.

LncRNA NEAT1 facilitates survival and angiogenesis in oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs) via targeting miR-377 and upregulating SIRT1, VEGFA, and BCL-XL.

OBJECTIVE: The present study was designed to investigate the mechanism by which lncRNA NEAT1 regulates survival and angiogenesis in oxygen-glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs). METHODS: OGD-treated BMECs were used to mimic cerebral ischaemia in vitro. The expression of lncRNA NEAT1 and miR-377 and proteins including VEGFA, SIRT1, and BCL-XL were measured by real-time quantitative PCR (qRT-PCR) and western blot, respectively. Cell viability and caspase 3 activity of BMECs under different conditions were determined using MTT and caspase activity assays, respectively. Matrigel-based angiogenesis assays were employed to evaluate the effect of lncRNA NEAT1 on angiogenesis. A dual-luciferase reporter assay was used to validate direct binding of miR-377 to putative targets. RESULTS: OGD exposure reduced the cell viability of BMECs. Upregulation of lncRNA NEAT1 and downregulation of miR-377 were also observed under OGD conditions. Knockdown of lncRNA NEAT1 inhibited angiogenesis and aggravated apoptosis in OGD-induced BMECs. Meanwhile, the expression level of miR-377 was upregulated while its downstream targets (VEGFA, SIRT1, and BCL-XL) were downregulated after lncRNA NEAT1 knockdown. Furthermore, miR-377 inhibited the angiogenesis and survival of OGD-induced BMECs. The expression of VEGFA, SIRT1, and BCL-XL were all attenuated by miR-377 overexpression. The dual-luciferase reporter assay proved miR-377 targeted the 3' UTR sequences of lncRNA NEAT1, VEGFA, SIRT1, and BCL-XL. CONCLUSION: lncRNA NEAT1 facilitated the survival and angiogenesis of OGD-induced BMECs via targeting miR-377 and promoting the expression of VEGFA, SIRT1, and BCL-XL, suggesting that lncRNA NEAT1 could be a promising target for cerebral ischaemia treatment.

[Diagnostic value of osseous diversity on CT to sinonasal inverted papilloma].

OBJECTIVE: To evaluate the CT characteristics of osseous diversity in patients with sinonasal inverted papilloma (SIP) and to correlate these characteristics with the origins of tumors. METHODS: Sinonasal CT images of 28 patients were reviewed retrospectively to detect areas within which there was focal hyperostosis. The correlation between the sites on the CT scans within which there was osseous diversity and the origin of the tumors in the surgery was analyzed. RESULTS: Surgical evaluation of 22 lesions with focal hyperostosis in CT images revealed that 20 of these lesions coincided with the actual origin of tumor. The focal hyperostosis on CT images corresponded to the actual tumor origin in 71.4% of cases. It denotes the origin of SIP could be predicted from the focal hyperostosis site. The origin of the other 2 cases were disaccord with the focal hyperostosis site, one case had the origin of uncinate process but hyperostosis of anterior middle turbinate, another case had the origin of superior turbinate but hyperostosis of uncinate process. Nine lesions of 28 patients had air sign, 21 lesions had bone absorption and destruction and 19 lesions had bone displacement in CT images. The pressure from tumor growth can induce varied bone destruction and displacement, the source of SIP can be estimated by the bone destruction site and displacement direction. CONCLUSIONS: There has a relatively high concordance between the origin of the SIP and focal hyperostosis on CT, The source of SIP could be discerned indirectly by bone destruction and displacement, these conduce to assess the disease before surgery and make pertinent operation.

[Cochlear implantation with suprameatal approach in Chinese children].

OBJECTIVE: To investigate the technique of the suprameatal approach for cochlear implantation in Chinese profound sensory hearing loss children. METHODS: Suprameatal approach for cochlear implantation were used in 50 cases (total 53 ears) with profound sensory hearing loss from May 2005 to January 2007. The electrode was passed through the suprameatal tunnel and went between the incus and chorda tympani into the scala tympani. RESULTS: Electrodes were completely inserted in 51 ears. There were no postoperative complications in all cases. Although the long effect need to be observed, all cases received better hearing and speech development benefit from cochlear implantation in the follow-up period. Among the 50 cases, 26 had speech perception in the open condition; 18 patients could speak short sentences although not clearly; and 6 patients learned to speak individual words only. CONCLUSIONS: The suprameatal approach was found to be a simple and safe technique that does not need mastoidectomy and avoid endangering the facial nerve and the chorda tympani. It enables wide exposure of middle ear and is especially suitable for cases with narrow facial recess or anteriorly located facial nerve.