Preventive treatment with sodium para-aminosalicylic acid inhibits manganese-induced apoptosis and inflammation via the MAPK pathway in rat thalamus.

Excessive exposure to manganese (Mn) may lead to neurotoxicity, referred to as manganism. In several studies, sodium para-aminosalicylic acid (PAS-Na) has shown efficacy against Mn-induced neurodegeneration by attenuating the neuroinflammatory response. The present study investigated the effect of Mn on inflammation and apoptosis in the rat thalamus, as well as the underlying mechanism of the PAS-Na protective effect. The study consisted of sub-acute (Mn treatment for 4 weeks) and sub-chronic (Mn and PAS-Na treatment for 8 weeks) experiments. In the sub-chronic experiments, pro-inflammatory cytokines, namely tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and cyclooxygenase 2 (COX-2) were significantly increased in the Mn-exposed group compared to the control II. PAS-Na treatment led to a significant reduction in the Mn-induced neuroinflammation by inhibiting IL-1ß and COX-2 mRNA expression and reducing IL-1ß secretion and JNK/p38 MAPK pathway activity. Furthermore, immunohistochemical analysis showed that the expression of caspase-3 was significantly increased in both the sub-acute and sub-chronic experimental paradigms concomitant with a significant decrease in B-cell lymphoma 2 (Bcl-2) in the thalamus of Mn-treated rats. PAS-Na also decreased the expression levels of several apoptotic markers downstream of the MAPK pathway, including Bcl-2/Bax and caspase-3, while up-regulating anti-apoptotic Bcl-2 proteins. In conclusion, Mn exposure led to inflammation in the rat thalamus concomitant with apoptosis, which was mediated via the MAPK signaling pathway. PAS-Na treatment antagonized effectively Mn-induced neurotoxicity by inhibiting the MAPK activity in the same brain region.

Efficacy and safety of Yaobitong capsule for acute lumbar disc herniation: A protocol for a multi-center randomized controlled trial.

BACKGROUND: There are few effective conservative therapies for acute lumbar disc herniation (LDH), and the choice of nonsteroidal anti-inflammatory drugs is not recommended for all patients. The purpose of this study was to compare the effect of Yaobitong capsule with celecoxib capsule, and to further confirm the safety and efficacy of Yaobitong capsule. METHODS: This study is a large sample multicenter randomized controlled trial. Eight hospitals served as sub centers to recruit patients. A total of 258 patients are divided into Yaobitong group and celecoxib group according to the ratio of 1:1. Celecoxib or Yaobitong capsule was taken orally for 14 days. Patients will complete the trial after 3 months of follow-up, and independent statisticians who are blinded to random assignment will analyze the data using SAS 9.3 software. The primary outcome was the visual analogue scale (VAS) score after 14 days of treatment, and Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and SF-12 will be regarded as secondary outcomes. Safety indexes will be recorded before and after treatment, and adverse events (AEs) will be recorded throughout this trial. DISCUSSION: This study will evaluate the efficacy and safety of Yaobitong capsule in treating LDH. The experimental results will provide evidence support to treat LDH with Yaobitong capsule.

Clinical Comparative Study of Different Fundus Imaging Methods in the Acute Phase of Vogt-Koyanagi-Harada Disease.

Background: The diversification of follow-up ophthalmic imaging examination methods, and whether there are differences in clinical characteristics of VKH at the acute stage under different images. Our study aims to compare the imaging characteristics of the acute phase of Vogt-Koyanagi-Harada disease (VKH) under different fundus imaging methods to deepen clinical knowledge. Methods: A retrospective case study was performed on fundus images of 62 eyes from 31 patients with acute phase VKH and a disease duration ≤2 months who were treated at Ganzhou People's Hospital from January 2013 to December 2020. Fundus photography (FP), optical coherence tomography (OCT), and fundus fluorescein angiography (FFA) were performed on all 62 eyes. The fundus presentations were divided into an optic disc swelling (ODS) group, a serous retinal detachment (SRD) group, and a mixed type (MT) group (both ODS and SRD), and the proportions of patients in these groups and the coincidence rate of ODS, SRD, and MT identified by the three fundus imaging modes were determined. Results: The proportion of patients with ODS was highest under FP, and the proportion of patients with MT was highest under OCT. The proportions of patients with ODS and MT in the three fundus imaging modes differed significantly (P < 0.05), while the proportion of patients with SRD did not (P > 0.05). The proportion of patients with subretinal fluid with positive OCT results was significantly higher than those with positive FFA results (81.08% vs. 59.46%) (P < 0.05). Conclusion: Clinically significant positive signs could be obtained for acute VKH under different imaging methods. However, compared with FP and FFA, OCT tomography is more intuitive for the observation of lesions.

Efficiency of oro-facial myofunctional therapy in treating obstructive sleep apnoea: A meta-analysis of observational studies.

OBJECTIVE: The literature on oro-facial myofunctional therapy (OMT) in children and adults with obstructive sleep apnoea (OSA) was systematically reviewed to investigate the effects of OMT on patients with OSA by age and disease severity to verify the effect of OMT on OSA. DATA SOURCES: All the comparative literature was retrieved from the PubMed, Embase and Cochrane libraries. METHOD: We searched the articles published up to 12 February 2022 and followed the preferred reporting project for systematic review and meta-analysis of reports. The quality of the studies was evaluated using the Newcastle-Ottawa scale. RESULTS: Of the primary indicators for evaluating OSA, 13 studies reported on the apnoea index (AHI), showing a decrease in the mean standard deviation of AHI from before OMT to after OMT (p < .00001). The lowest oxygen saturation was reported in nine studies, and the mean standard deviation of the lowest oxygen saturation increased from before to after OMT (p = .0009). Ten studies reported the Epworth Sleepiness Scale (ESS), indicating that the mean standard deviation of the ESS decreased from before to after OMT (p < .00001). The subgroup analysis showed that the AHI scores indicating mild and moderate OSA were significantly reduced, and the AHI scores indicating severe OSA also decreased, but this was not statistically significant. The lowest oxygen saturation increased obviously in patients with both mild and moderate and severe OSA. Of the secondary indicators of OSA, there was a statistically significant improvement in snoring intensity (p = .0002). CONCLUSION: Oral and facial muscular function therapy can be used as a simple and non-invasive new technique to improve the AHI, minimum oxygen saturation, ESS, and snoring intensity in patients with mild and moderate OSA and the lowest oxygen saturation in patients with severe OSA.

Efficacy and safety of Daoyin and massage for lumbar disc herniation: A protocol for overview of systematic reviews.

BACKGROUND: Lumbar disc herniation (LDH) is a common disease, which can cause low back pain, sciatica, and even disability. The treatment of LDH is a global challenge. Conservative therapy with non-drugs is considered to be the first choice for patients with LDH. In recent years, an increasing number of systematic reviews and meta analyses on Daoyin and massage interventions in lumbar disc herniation have been implemented. However, the evidence quality and methodological quality of these systematic reviews/meta analyses are unknown and need to be systematically evaluated. This overview aims to systematically summarize and critically appraise the current evidence on Daoyin and massage for LDH. METHODS: Eight electronic data will be retrieved, including China National Knowledge Infrastructure (CNKI), Wanfang database (WF), China Biomedical database (CBM), Chinese Scientific Journals Database (VIP), PubMed, Cochrane Library, Web of Science (WOS), and EMBASE from their inception to March 1, 2022. The reporting quality, methodological quality, risk of bias, quality of evidence will be assessed by using The Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 (PRISMA 2020), the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Review (ROBIS), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Two independent researchers conducted literature screening, data extraction, and quality evaluation process. In addition, we will establish an overlap matrix and calculate the corrected covered area to evaluate the impact of overlapping areas on conclusions. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: This overview will provide comprehensive evidence of Daoyin and massage for treating lumbar disc herniation. SYSTEMATIC REVIEW REGISTRATION: INPLASY202210019.

Therapeutic of Candesartan and Music Therapy in Diabetic Retinopathy with Depression in Rats.

This study aimed to investigate the therapeutic effects of candesartan combined with music therapy on diabetic retinopathy with depression and to assess the molecular mechanisms. Associated animal model of diabetes mellitus and depression was established in rats. Pathological changes in the hippocampus were detected by haematoxylin eosin (H&E) staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was used to detect retinal cell apoptosis. Angiotensin II (Ang II) in peripheral blood and neurotransmitters, including serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the hippocampus, was measured by enzyme linked immunosorbent assay (ELISA). Fluorescence quantitative PCR and western blotting were used to detect the expression of brain-derived neurotrophic factor (BDNF) and c-fos in the hippocampus. Our data showed that chromatin aggregation and cytoplasmic vacuolation were observable in the hippocampal cells of the rats in the model group, while candesartan and music therapy could reduce morphological changes in the hippocampus of diabetic rats with depression. Compared with the control group, the apoptosis of retinal cells was significantly higher, the contents of 5-HT, DA, and NE in the hippocampus were significantly lower, Ang II level in peripheral blood was significantly higher, and the expression of BDNF and c-fos in the hippocampus decreased significantly in the model group. By contrast, candesartan or candesartan + music therapy ameliorated the changes in retina cell apoptosis, reduction of neurotransmitters, increase in AII, and the expression of c-fos and BDNF. Especially, music therapy further improved the effects of candesartan on retina cell apoptosis and neurotransmitter release in diabetic retinopathy rats with depression. In conclusion, candesartan and music therapy have an additive effect in DM with both visual impairment and depression, which might serve a potential alternative treatment for this complex disease.

Berberine improves dietary-induced cardiac remodeling by upregulating Kruppel-like factor 4-dependent mitochondrial function.

Multiple studies have showed that berberine protects against heart diseases, including obesity-associated cardiomyopathy. However, it is not fully disclosed the potential molecular mechanisms of berberine on controlling cardiac remodeling. Kruppel-like factor (KLF) 4, identified as a critical transcriptional factor, participates in multiple cardiac injuries. The present study was to explore whether KLF4 determined the cardioprotective benefits of berberine in dietary-induced obese mice. High fat diet-induced obese mice were treated with berberine with or without lentivirus encoding Klf4 siRNA, and cardiac parameters were analyzed by multiple biological approaches. In dietary-induced obese mouse model, administration of berberine obviously increased cardiac level of KLF4, which closely correlated with improvement of cardiac functional parameters. Co-treatment of lentivirus encoding Klf4 siRNA abolished cardioprotective benefits of berberine, including induction of cardiac hypertrophy, fibrosis, functional disorders, inflammatory response and oxidative stress. Mechanistically, we found berberine improved cardiac mitochondrial biogenesis and activities, whereas silencing Klf4 decreased berberine-upregulated mitochondrial quality, ATP production and oxygen consumption. Our present study demonstrated that berberine protected against dietary-induced cardiac structural disorders and mitochondrial dysfunction dependent on cardiac KLF4 signaling. Cardiac KLF4 was one of potential therapeutic targets for obesity-induced cardiac injuries.

A meta-analysis of randomized controlled trials: Efficacy of selenium treatment for sepsis.

BACKGROUND: To understand the clinical outcomes of selenium therapy in patients with sepsis syndrome, we conducted a meta-analysis of randomized controlled trials (RCT). METHODS: A total of 13 RCTs comparing selenium and placebo for patients with sepsis were reviewed systematically. RESULTS: However, we could not detect the association of selenium treatment with a decreased mortality at different time course (relative risk [RR] [95% confidence interval, CI]: 0.94 [0.82-1.06] at day 28; 0.73 [0.36-1.47] at day 90; 1.16 [0.78-1.71] at 6 months; respectively). Selenium supplementation did not show favorable efficacy in the incidence of renal failure, secondary infection or duration of mechanical ventilation (RR [95% CI]: 0.65 [0.41-1.03]; 0.96 [0.87-1.06]; standard mean difference [SMD] [95% CI]: 0.17 [-0.30-0.63]; respectively). Interestingly, we found that selenium therapy was benefit for sepsis patients with reduced duration of vasopressor therapy, staying time in intensive care unit and hospital, and incidence of ventilator-associated pneumonia (SMD [95% CI]: -0.75 [-1.37 to -0.13]; -0.15 [CI: -0.25 to -0.04]; -1.22 [-2.44 to -0.01]; RR [95% CI]: 0.61 [0.42-0.89]; respectively). CONCLUSION: Based on our findings, intravenous selenium supplementation could not be suggested for routine use.

The role of NLRP3 inflammasome in stroke and central poststroke pain.

BACKGROUND: NLRP3 inflammasome plays a prominent role in the pathogenesis and progression of many diseases, such as type 2 diabetes mellitus, obesity, atherosclerosis, and Alzheimer's disease. However, little knowledge is known about the role of NLRP3 inflammasome in central post-stroke pain (CPSP). METHODS: We selected relevant studies by searching PubMed, Embase, and Medline from inception through February, 2018. We systematically reviewed available publications according to the terms "NLRP3 inflammasome" and "stroke" or "central post-stroke pain" in the title/abstract field. RESULTS: We reviewed the articles and put forward two possible ways for NLRP3 inflammasome in CPSP. One way is that NLRP3 activation causes cerebral cortex injure, decreasing descending projection fiber to thalamus. Such condition may let GABAergic releases reduce, making the ventral basal (VB) neurons excitability increased. Finally, CPSP occur. Another way is that NLRP3 inflammasome leads to thalamic lesion and strengthens inflammatory response of microglia at the same time. Persistent inflammation causes GABAergic alteration in thalamus reticular neurons (TRN) to restrain VB interneurons functions, contributing to CPSP. CONCLUSIONS: These possible mechanisms will help become knowledgeable about the occurrence CPSP and provide potential therapy for CPSP.

Magnetic Resonance Spectroscopy for Evaluating the Effect of Pulsed Electromagnetic Fields on Marrow Adiposity in Postmenopausal Women With Osteopenia.

OBJECTIVE: Pulsed electromagnetic fields (PEMFs) could promote osteogenic differentiation and suppress adipogenic differentiation in bone mesenchymal stem cells ex vivo. However, data on the effect of PEMF on marrow adiposity in humans remain elusive. We aimed to determine the in vivo effect of PEMF on marrow adiposity in postmenopausal women using magnetic resonance spectroscopy. METHODS: Sixty-one postmenopausal women with osteopenia, aged 53 to 85 years, were randomly assigned to receive either PEMF treatment or placebo. The session was performed 3 times per week for 6 months. All women received adequate dietary calcium and vitamin D. Bone mineral density (BMD) by dual-energy x-ray absorptiometry, vertebral marrow fat content by magnetic resonance spectroscopy, and serum biomarkers were evaluated before and after 6 months of treatment. RESULTS: A total of 27 (87.1%) and 25 (83.3%) women completed the treatment schedule in the PEMF and placebo groups, respectively. After the 6-month treatment, lumbar spine and hip BMD increased by 1.46% to 2.04%, serum bone-specific alkaline phosphatase increased by 3.23%, and C-terminal telopeptides of type 1 collagen decreased by 9.12% in the PEMF group (P < 0.05), whereas the mean percentage changes in BMD and serum biomarkers were not significant in the placebo group. Pulsed electromagnetic field treatment significantly reduced marrow fat fraction by 4.81%. The treatment difference between the 2 groups was -4.43% (95% confidence interval, -3.70% to -5.65%; P = 0.009). CONCLUSIONS: Pulsed electromagnetic field is an effective physiotherapy in postmenopausal women, and this effect may, at least in part, regulate the amount of fat within the bone marrow. Magnetic resonance spectroscopy may serve as a complementary imaging biomarker for monitoring response to therapy in osteoporosis.

[Study on configuration fabric and germinative conditions of Salvia miltiorrhizy seeds].

OBJECTIVE: To provide theoretic warrant and technical reference for Salvia miltiorrhizr standardization planting, by carrying out various systemic studies such as observation of seeds configuration fabric, idiosyncrasy of water absorption and groping germinating conditions. METHOD: In the study of configuration fabric, seeds were observed and taken photos by scanning electronic microscope, and heft method was used for measuring changes of water absorption velocity and dehydration velocity. Seeds germination conditions were probed into under the national test regulations for crop seeds and related prescription from international standards. RESULT: (1) There was a layer of slime about 10-20 microm thickness covering epicarp of Danshen seeds. The slime formed as diamond meshwork (reseau) and the weight of it was 8%-10% of total seeds weight. (2) The speed of water absorption of seeds was extremely rapid. The weight of seeds could increase above 10 times as original while the dehydration velocity was quite low. (3) The optimal temperature for the seeds germination is around 25 degrees C, and the germination rate of the new seeds gained yearly was above 75%, but the rate would decrease sharply as years went by. It was also found that the seeds germination power and exponent of vigor were quite high under the temperature transformation between 23 degrees C, 28 degrees C. Such treatments as pre-cool, PEG treatment and infusing with GA3 could increase the rate of seeds germination capacity obviously.