Myricetin mitigates motor disturbance and decreases neuronal ferroptosis in a rat model of Parkinson's disease.

Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP+), respectively. Ferroptosis was identified by assessing the levels of Fe2+, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe2+, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP+-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP+-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.

Association of body mass index with rapid eye movement sleep behavior disorder in Parkinson's disease.

Background: The association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson's disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients. Methods: In this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson's Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models. Results: We identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results. Conclusion: The current study found a significant dose-response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.

Acupuncture and moxibustion treatment for myasthenia gravis: A systematic review and meta-analysis.

BACKGROUND: Myasthenia gravis (MG) is a common autoimmune disease that often involves the skeletal muscle of the whole body and seriously affects patients' quality of life. Acupuncture and moxibustion treatment of MG has unique advantages, the aim is to evaluate the clinical effect of acupuncture and moxibustion on MG. METHODS: The literature on acupuncture and moxibustion treating MG in PubMed, CochraneLibrary, EMBASE, SCI, China Academic Journals full-text database, China Biology Medicine disc, VIP and Wanfang database were searched through computers from the establishment of the database to December 2022. RESULTS: A total of 11 studies were included, involving 658 patients, where 330 in the treatment group and 328 in the control group. The results of the meta-analysis showed that the treatment group performed better than the control group in improving the total clinical response rate (OR = 3.26, 95%[2.04,5.21], P < .01). Additionally, the treatment group outperformed the control group in raising the absolute clinical score (MD = -3.48, 95%CI[-5.17, -1.78], P < .01). However, there was no significant difference between the treatment group and the control group in improving the level of serum interleukin-6 receptor (MD = -1.45,95%CI[-6.85,3.95], P > .05) and OMG quantitative score (MD = -2.16,95%CI[-4.85,0.52], P > .05). The total clinical effective rate was tested for publication bias, which showed that the 2 sides of the funnel plot were asymmetrical, suggesting the possible existence of publication bias. CONCLUSION: Acupuncture and moxibustion has a good effect on MG, which is better than conventional Western medicine in improving the total clinical effective rate and absolute clinical score.

Establishment and validation of an efficient method for the 3D culture of osteoclasts in vitro.

INTRODUCTION: Osteoclasts (OCs) play a crucial role in maintaining bone health. Changes in OC activity are linked to different bone diseases, making them an intriguing focus for research. However, most studies on OCs have relied on 2D cultures, limiting our understanding of their behavior. Yet, there's a lack of knowledge regarding platforms that effectively support osteoclast formation in 3D cultures. METHODS: In our investigation, we explored the capacity of collagen and GelMA hydrogels to facilitate osteoclast development in 3D culture settings. We assessed the osteoclast development by using different hydrogels and cell seeding strategies and optimizing cell seeding density and cytokine concentration. The osteoclast development in 3D cultures was further validated by biochemical assays and immunochemical staining. RESULTS: Our findings revealed that 0.3 % (w/v) collagen was conducive to osteoclast formation in both 2D and 3D cultures, demonstrated by increased multinucleation and higher TRAP activity compared to 0.6 % collagen and 5 % to 10 % (w/v) GelMA hydrogels. Additionally, we devised a "sandwich" technique using collagen substrates and augmented the initial macrophage seeding density and doubling cytokine concentrations, significantly enhancing the efficiency of OC culture in 3D conditions. Notably, we validated osteoclasts derived from macrophages in our 3D cultures express key osteoclast markers like cathepsin K and TRAP. CONCLUSIONS: To conclude, our study contributes to establishing an effective method for cultivating osteoclasts in 3D environments in vitro. This innovative approach not only promises a more physiologically relevant platform to study osteoclast behavior during bone remodeling but also holds potential for applications in bone tissue engineering. CLINICAL SIGNIFICANCE: This study introduces an efficient method for cultivating osteoclasts in 3D environments in vitro. It offers a more physiologically relevant platform to investigate osteoclast behavior and holds promise to advance research in bone biology and regenerative dentistry.

The interaction effect of depressive symptoms and inflammation on the occurrence of cardiovascular diseases.

BACKGROUND: Whether there was an interaction effect between depressive symptoms and inflammation on the occurrence of cardiovascular diseases (CVDs) was unclear. METHODS: In this cross-sectional study, 3346 participants in the National Health and Nutrition Examination Survey (NHANES) were included. Multivariable regression analysis was performed to explore the associations of depressive symptoms or inflammation with CVDs. The attributable proportion of interaction (API), and synergy index (SI) were applied for evaluating the statistical significance of the interaction effect. RESULTS: Depressive symptoms were associated with 2.31-fold risk of CVDs [odds ratio (OR) = 2.31, 95 % confidence interval (CI): 1.47-3.62). The increased risk of CVDs was observed in people with neutrophil to lymphocyte ratio (NLR) ≥1.88 group (OR = 1.36, 95%CI: 1.01-1.85) and neutrophil/[white blood cell (WBC)-neutrophil] ≥1.35 (OR = 1.52, 95%CI: 1.12-2.07) after adjusting for confounders. The interaction effect of depressive symptoms and high NLR on the risk of CVDs was statistically significant with an OR value of 2.60 (95%CI: 1.43-4.70) compared to low NLR and no depressive symptoms group after adjusting for confounders. The API was 0.66 (95%CI: 0.44-0.89) and SI was 4.23 (95%CI: 2.08-8.59). The interaction effect of depressive symptoms and high neutrophil/(WBC-neutrophil) was associated with the risk of CVDs compared to low neutrophil/(WBC-neutrophil) and no depressive symptoms group (OR = 3.59, 95%CI: 2.00-6.45). The API was 0.78 (95%CI: 0.63-0.93) and SI was 6.75 (95%CI: 3.55-12.82). CONCLUSION: There was an interaction effect of depressive symptoms and inflammation on the occurrence of CVDs.

Autonomic function and motor subtypes in Parkinson's disease: a multicentre cross-sectional study.

Autonomic symptoms (AS) are critical in Parkinson's disease (PD). We aimed to determine the relative significance of clinical factors allowing predictions about incidence of AS, and examine AS profiles among PD patients by motor subtype and its relation to AS. The cross-sectional data of a multicentre sample, including 714 PD patients and 194 healthy controls from Parkinson's Progression Marker Initiative study and Pingchan granule study were analyzed, stratified by PD subtypes [postural instability and gait disturbances (PIGD), tremor dominant (TD), and indeterminate] and domain autonomic dysfunction. Compared with healthy controls, PD patients scored higher in the total Scales for Outcomes in Parkinson's Disease-Autonomic dysfunction score and in several domain scores in particular, and there was a significant overlap in domain AS. Risk factors of individual domain autonomic dysfunction were heterogeneous. PIGD and indeterminate were the predominant subtypes in pupillomotor and thermoregulatory symptoms. TD and indeterminate were more likely to suffer from cardiovascular problem. The odd in sexual dysfunction was significant for PIGD. Gastrointestinal and urinary symptoms seemed not to be associated with a specific subtype. Our study demonstrated that AS were highly heterogeneous and 3 subtypes differed in autonomic performance, providing clues to understand mechanisms underlying AS in PD.

Retraction: Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold.

Retraction of 'Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold' by Donghai Li et al., Biomater. Sci., 2018, 6, 519-537, https://doi.org/10.1039/C7BM00975E.

Oral traditional Chinese medicine for vestibular Migraine: A systematic review and meta-analysis.

OBJECTIVE: Vestibular migraine is a common vertigo disease, and studies confirm that Traditional Chinese medical has unique advantages in treating vestibular migraine. However, there is no unified clinical treatment method and lacks objective outcome indicators. This study aims to provide evidence-based medical evidence by systematically evaluating the clinical efficacy of oral TCM in treating vestibular migraine. METHODS: Search journals related with clinical randomized controlled trials of oral traditional Chinese medicine for vestibular migraine in databases includes China Academic Journals full-text database (CNKI), China Biology Medicine disc (CBM), China Science and Technology Journal Database(VIP), Wangfang Medicine Online(WANFANG), PubMed, Cochrane library, EMBASE, MEDLINE, and OVID databases from their inceptions until September 2022. The quality of the included RCTs was assessed using the Cochrane risk of bias tool, then conduct the Meta analysis by using RevMan5.3. RESULTS: There were 179 papers left after selection. Moreover, according to the literature inclusion and exclusion criteria, 158 studies were filtered and the remaining 21 articles would be considered in this paper, which include 1650 patients in total and 828 of them were in the therapy group and 822 of them were in the control group.Furthermore,the therapy group outperformed the control group in terms of the total efficiency rate and TCM syndrome score, and the difference is statistically significant(P < 0.01). The number of vertigo attacks and the duration of each vertigo decreased compared to the control group, which difference is also statistically significant (P < 0.01). The funnel chart of the total efficiency rate was approximately symmetric and publication bias was low. CONCLUSION: The oral traditional Chinese medicine is an effective way for vestibular migraine, which would help with the clinical symptoms, reduce the TCM syndrome score, decrease the number of vertigo attacks and the duration of each vertigo, and improve life quality of patients.

Polydopamine-coated 3D-printed ß-tricalcium phosphate scaffolds to promote the adhesion and osteogenesis of BMSCs for bone-defect repair: mRNA transcriptomic sequencing analysis.

Cellular bioactivity and tissue regeneration can be affected by coatings on tissue-engineered scaffolds. Using mussel-inspired polydopamine (PDA) is a convenient and effective approach to surface modification. Therefore, 3D-printed ß-tricalcium phosphate (ß-TCP) scaffolds were coated with PDA in this study. The effects of the scaffolds on the adhesion and osteogenic differentiation of seeded bone marrow mesenchymal stem cells (BMSCs) in vitro and on new-bone formation in vivo were investigated. The potential mechanisms and related differential genes were assessed using mRNA sequencing. It was seen that PDA coating increased the surface roughness of the 3D-printed ß-TCP scaffolds. Furthermore, it prompted the adhesion and osteogenic differentiation of seeded BMSCs. mRNA sequencing analysis revealed that PDA coating might affect the osteogenic differentiation of BMSCs through the calcium signaling pathway, Wnt signaling pathway, TGF-beta signaling pathway, etc. Moreover, the expression of osteogenesis-related genes, such as R-spondin 1 and chemokine c-c-motif ligand 2, was increased. Finally, both the 3D-printed ß-TCP scaffolds and PDA-coated scaffolds could significantly accelerate the formation of new bone in critical-size calvarial defects in rats compared with the control group; and the new bone formation was obviously higher in the PDA-coated scaffolds than in ß-TCP scaffolds. In summary, 3D-printed ß-TCP scaffolds with a PDA coating can improve the physicochemical characteristics and cellular bioactivity of the scaffold surface for bone regeneration. Potential differential genes were identified, which can be used as a foundation for further research.

The Importance of Early Identification for Parkinson's Disease Patients with Postural Instability and Gait Disturbance.

Background: More and more evidence-based medicine has proved that Parkinson's disease (PD) patients of tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtype express great individual differences and heterogeneity. Early identification of different subtypes may be an important way to delay disease progression and improve patients' prognosis. Objective: The study aimed to compare the spectrum of motor symptoms (MS) and nonmotor symptoms (NMS) between TD and PIGD dominant in the early and middle stages of PD, and determine predictive factors that are associated with different motor subtypes. Methods: 292 PD patients in this study were divided into TD-PD and PIGD-PD, and the clinical characteristics between different motor subtypes were compared based on scales related to sleep, mood, and autonomic function. Univariate and multivariate ordered logistic regression analyses were used to analyze the independent influencing factors of disease severity between different motor subtypes. Through the establishment of binary logistic regression model, the potential independent risk factors for distinguishing TD-PD and PIGD-PD were studied. Results: Compared with TD subtype, patients with PIGD subtype have longer course of disease, higher disease severity, and higher daily dosage of levodopa. The severity of nontremor motor symptoms in PIGD-PD is greater than that of TD subtype. Only PIGD score was independently associated with disease severity for the two motor subtypes. Meanwhile, high scores (LED, total UPDRS, PIGD score, gastrointestinal, thermoregulatory, RBDSQ) and low tremor scores were the potential independent risk factors for distinguishing PIGD-PD from TD-PD. Conclusion: Specific nonmotor symptoms (RBD, gastrointestinal function and thermoregulation function) were associated with the PIGD subtype. Prompt detection and early treatment of NMSs related to the PIGD subtype based on the treatment of motor symptoms may improve patient outcomes.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Association of Blood Amyloid Beta-Protein 1-42 with Poststroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

Background: Increases in blood of amyloid beta-protein (Aß) have been noted in patients with Alzheimer's dementia (AD). Recent studies have shown that blood amyloid beta-protein 1-42 (Aß1-42) level is closely related to poststroke cognitive impairment (PSCI), which may be the influencing factor and even a predictor of PSCI. The aim of this systematic review was to synthesize the evidence for the association of cognitive impairment among PSCI. Methods: PubMed (MEDLINE), EMBASE, Cochrane Library, the Cochrane Central Register of Controlled Trial (CENTRAL), CNKI, and WanFang data were searched. Case-control, cohort, and cross-sectional studies that evaluated the association between blood Aß1-42 and PSCI were included irrespective of language and date of publication. The outcomes of this review consisted of (1) any dementia, (2) any cognitive impairment, and (3) any cognitive impairment no dementia, which were assessed at least 3 months (90 days) after stroke. Exposure of interest was blood Aß1-42 level (including serum and plasma). Results: Of 617 records retrieved, 8 studies (6 case-control and 2 cohort studies) involving 931 stroke patients were included for further analysis. 8 studies with 931 subjects explored the correlation between Aß1-42 and PSCI. PSCI was reported in 457 patients, and the pooled SMD of amyloid beta-protein 1-42 was -0.96 (95% CI -1.10~-0.82, I 2 = 15%, P < 0.01). The results remained robust in sensitivity analysis adjusting for study quality, sample source, and cognitive scale score in analysis of studies, as well as in analysis adjusted for publication bias. Conclusions: Blood Aß1-42 level was significantly negatively related to the risk for PSCI, and more prospective studies with large sample size are needed to define a precise threshold value of blood Aß1-42 level to predict PSCI in the future. This study is registered with PROSPERO, registration number: CRD42021246165.

Pingchan Granule for Motor Symptoms and Non-Motor Symptoms of Parkinson's Disease: A Randomized, Double-Blind, Placebo-Controlled Study.

Background: Pingchan granule (PCG) is a traditional Chinese medicine for treating Parkinson's disease (PD). Objective: This study aimed at evaluating the efficacy and safety of PCG for motor and non-motor symptoms of PD. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 292 participants with mild-to-moderate PD were included and followed for 36 weeks (24 week treatment, 12-week follow-up after intervention), randomly assigned at a 1:1 ratio to receive PCG or placebo. The primary outcomes included the severity of motor symptoms assessed by the Unified Parkinson's disease Rating Scale (UPDRS) part 3 (UPDRS-III) score and the rate of disease progression assessed by the total UPDRS score. Secondary outcomes included non-motor symptoms assessed using the Scale for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), Parkinson's disease Sleep Scale (PDSS), 24-item Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), UPDRS part 2 (UPDRS-II), and 39-item Parkinson's Disease Questionnaire (PDQ-39) scores. Assessments were done at baseline (T0), 12 weeks (T1), 24 weeks (T2), and 36 weeks (T3). Results: Generalized estimating equation analyses revealed that the PCG group had significantly better improvement in UPDRS-III score at T1, T2, and T3 [time-by-group interaction, T1: ß, -0.92 (95% CI, -1.59--0.25; p = 0.01); T2: ß, -2.08 (95% CI, -2.90--1.27; p < 0.001); T3: ß, -4.54 (95% CI, -5.37--3.71; p < 0.001))]. The PCG group showed a greater decrease (rate of disease change) in the total UPDRS score between T0 and T2 [-2.23 (95% CI, -2.72--1.73; p < 0.001) points per week vs. -0.21 (95% CI, -0.80-0.39; p = 0.50) points per week in the placebo group, p < 0.001]. Ameliorations of SCOPA-AUT, PDSS, HAM-D, HAM-A, UPDRS-II, and PDQ-39 scores were also observed. Conclusion: PCG had a long-lasting and extensive symptomatic efficacy for both motor and non-motor symptoms of PD with good tolerance. Trial registration: Chinese Clinical Trial Register, ChiCTR-INR-17011949.

Electroacupuncture for post-stroke overactive bladder: a multi-centre pilot randomized controlled trial.

BACKGROUND: Although acupuncture has been shown to be effective at treating overactive bladder (OAB) following stroke, to our knowledge, no randomized controlled trial (RCT) examining the effects of acupuncture on patients with post-stroke OAB has been conducted. The aim of this preliminary study was to explore the effects of electroacupuncture (EA) in the treatment of post-stroke OAB. METHODS: This study was a multi-site randomized, assessor-blind, controlled pilot trial of patients with post-stroke OAB. In all, 34 post-stroke subjects (mean age: 71.0 years; 32.4% female) with OAB symptoms were randomly assigned to the treatment group or control group in a 1:1 ratio. The subjects in the treatment group were treated with six sessions of EA for 4 weeks, while the subjects in the control group received usual care. The primary outcome measure was the overactive bladder symptom scale (OABSS). Secondary outcome measures included a three day bladder diary and the stroke-specific quality-of-life scale (SSQoL). RESULTS: EA showed a moderate effect size (ES) on the perceived severity of OAB symptoms as measured by the OABSS at week 5 (one week post-treatment, ES 0.57; p = 0.034) and week 8 (three weeks post-treatment, ES 0.60; p = 0.021), although the results did not remain statistically significant after Bonferroni correction for multiple testing. No significant differences in bladder diary parameters or SSQoL score were found. The EA treatment was well tolerated by the post-stroke subjects. CONCLUSION: A six-session EA treatment was feasible and appeared to reduce OAB symptoms in post-stroke patients. Further fully powered trials are warranted to confirm the efficacy of EA for those with post-stroke OAB.

Strontium Modified Calcium Sulfate Hemihydrate Scaffold Incorporating Ginsenoside Rg1/Gelatin Microspheres for Bone Regeneration.

The aim of this study was to prepare a promising biomaterial for bone tissue repair and regeneration. The Strontium - calcium sulfate hemihydrate (Sr-α-CaS) scaffold incorporating gelatin microspheres (GMs) encapsulated with Ginsenoside Rg1 (Rg1) was designed. The scaffolds of Rg1/GMs/Sr-α-CaS showed sustained release of Rg1, good biocompatibility and ability of promoting osteogenic differentiation and angiogenesis in vitro. The scaffolds were implanted into animal model of cranial bone defect to characterize bone tissue repair and regeneration in vivo. From the images of Micro-CT, it was obvious that the most bone tissue was formed in Rg1/GMs/Sr-α-CaS group in 12 weeks. New bone structure, collagen and mineralization were analyzed with staining of HE, Masson and Safranin O-Fast green and showed good distribution. The expression of osteocalcin of Rg1/GMs/Sr-α-CaS indicated new bone formation in defect site. The results revealed that synergy of Rg1 and Sr showed the best effect of bone repair and regeneration, which provided a new candidate for bone defect repair in clinic.

Repairing effects of glucosamine sulfate in combination with etoricoxib on articular cartilages of patients with knee osteoarthritis.

PURPOSE: To evaluate the repairing effects of glucosamine sulfate combined with etoricoxib on articular cartilages of patients with knee osteoarthritis (KOA). METHODS: A total of 106 KOA patients were randomly divided into control (n = 40) and experimental groups (n = 66) and treated with etoricoxib alone and glucosamine sulfate plus etoricoxib, respectively. Changes in WOMAC score and clinical efficacy were observed. The synovial fluid was extracted. Bone metabolism indices, growth factors, inflammatory factors, matrix metalloproteinases (MMPs), and NO-induced apoptosis-related factors were measured by ELISA. JNK and Wnt5a mRNA levels were determined using RT-PCR. RESULTS: After treatment, the total WOMAC scores of both groups significantly declined (P < 0.05), being lower in experimental group. The total effective rate of experimental group was higher (P < 0.05). BGP and OPG levels rose, especially in experimental group (P < 0.05). CTX-II, COMP, and RANKL levels decreased, particularly in experimental group (P < 0.05). TGF-ß, IGF-1, and FGF-2 levels increased, especially in experimental group (P < 0.05). Both groups, particularly experimental group, had decreased levels of IL-1ß, IL-17, IL-18, TNF-α, MMP-3, MMP-9, and MMP-13 (P < 0.05). JNK and Wnt5a mRNA levels of both groups dropped, which were lower in experimental group (P < 0.05). NO and LPO levels reduced, being lower in experimental group. SOD level rose, especially in experimental group (P < 0.05). CONCLUSION: Glucosamine sulfate plus etoricoxib can repair the articular cartilages of KOA patients. Probably, JNK and Wnt5a are downregulated to inhibit the secretion of MMPs through lowering the levels of inflammatory factors, thereby delaying cartilage matrix degradation. NO-induced chondrocyte apoptosis may be suppressed via the SOD pathway.

Efficacy of Additional Corticosteroid in a Multimodal Cocktail for Postoperative Analgesia Following Total Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Local injection of a multimodal cocktail including corticosteroid is commonly used for postoperative pain following total knee arthroplasty (TKA). However, it is inconclusive whether additional corticosteroid is beneficial. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy of an additional, local injection of corticosteroid in terms of pain relief and knee function recovery after TKA. METHODS: RCTs in electronic literature databases including PubMed, Web of Science, Embase, and Cochrane Library were systematically searched. Of 1,628 records identified, 9 RCTs involving 727 knees were eligible for data extraction and meta-analysis. RESULTS: Local injection of a multimodal cocktail including corticosteroid did not contribute to pain relief within 12 hours postoperatively (P > 0.05). However, from 24 hours to 72 hours, it significantly decreased pain scores (P < 0.05, all) at rest and reduced total rescue opioid consumption postoperatively (P < 0.05). Knee range of motion (ROM) was improved at postoperative day 1 (POD1) and POD2 (P < 0.05), and hospital stay (P < 0.05) was shortened after local injection of corticosteroid. However, the other outcomes, including knee ROM after POD2, C-reactive protein level, Knee Society score, postoperative nausea and vomiting, and wound complication occurrences, were not significantly different (P > 0.05, all). CONCLUSIONS: Additional corticosteroid added to a multimodal cocktail improved postoperative pain, enhanced knee functional recovery, and shortened hospital stays following TKA, but local injection of corticosteroids had no effect on reducing nausea and vomiting based on our outcomes.

Ameliorative effect of Xiaoyao-jieyu-san on post-stroke depression and its potential mechanisms.

A stroke is a severe life-threatening disease with high fatality and disability rate. This investigation aimed to study the effect of Xiaoyao-jieyu-san (XYJY) on post-stroke depression (PSD) and its potential mechanisms. PSD rats were prepared using middle cerebral artery embolization (MCAO) and chronic unpredictable mild stress (CUMS), and divided into six groups (n = 10)-sham; MCAO; MCAO + CUMS (PSD); PSD + fluoxetine (1.84 mg/kg/day, 4 weeks); and PSD + XYJY (450 mg/kg/day and 900 mg/kg/day, 4 weeks). Body weight recording, despair swimming test, and sucrose preference test were performed at 0, 3 and 7 weeks. Histopathological examination and levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor (BDNF) in ventral tegmental area-nucleus accumbens (VTA-NAc) tissue were determined at the end of a 7-week period. Real-time polymerase chain reaction PCR was used to determine mRNA expression of 5-HT1AR and 5-HT2AR, and Western blot was performed to determine expression of BDNF, corticotrophin-releasing factor (CRF), and cannabinoid receptors (CB1R and CB2R) in VTA-NAc tissue. High-performance liquid chromatography coupled with electrospray mass spectroscopy revealed that the constituents of XYJY are mainly paeoniflorin, imperatorin, naringin, arnesene, 2,3,5,4'-tetrahydroxyl-diphenylethylene-2-O-glucoside, kaempferol-3-O-rutinoside, quercetin, hesperidin, cycloastragenol and atractylenolide III. XYJY (900 mg/kg) increased the body weight of PSD rats, while XYJY (450 mg/kg and 900 mg/kg) shortened the duration of immobility and enhanced the sucrose preference of PSD rats. XYJY (450 mg/kg and 900 mg/kg) increased the levels of 5-HT, NE and BNDF, up-regulated mRNA expression of 5-HT1AR, down-regulated 5-HT2AR, and up-regulated BNDF, CB1R, and CB2R expression in the VTA-NAc tissue of PSD rats but down-regulated CRF. Collectively, the present findings suggested that XYJY has an ameliorative effect on PSD in rats via modulation of BNDF, cannabinoid receptors and CRF in VTA-NAc tissue.

A meta-analysis evaluates the efficacy of intravenous acetaminophen for pain management in knee or hip arthroplasty.

BACKGROUND: The objective of this study was to assess whether intravenous acetaminophen for patients undergoing knee or hip arthroplasty could reduce the opioid consumption and improve pain management. METHOD: Eligible studies were searched from electronic databases including PubMed, Web of Science, Embase (Ovid interface) and Cochrane Library (Ovid interface). The quality assessments were performed according to the Cochrane systematic review method. The assessed outcomes were including opioid consumption, pain scores, length of hospital stays and total occurrence of adverse events. RESULTS: Among 832 records identified, six randomized controlled trials (RCTs) and five non-RCTs were eligible for data extraction and meta-analysis. According to the outcomes, the patients receive intravenous acetaminophen had less total opioid consumption after knee or hip artroplasty (SMD = -0.66; 95%CI, -1.13 to -0.20), but they did not obtain statistical improvement of postoperative pain control at postoperative day 0 (POD0, SMD = -0,15; 95%CI, -0.36 to 0.07), POD1(SMD = 0,12; 95%CI, -0.13 to 0.36), POD2 (SMD = -0,29; 95%CI, -0.70 to 0.12) and POD3 (SMD = -0,04; 95%CI, -0.49 to 0.41). Meanwhile, there were similar outcomes about the length of hospital stays in patients whether or not receiving intravenous acetaminophen (SMD = -0,05; 95%CI, -0.26 to 0.15). And, the total adverse effects occurrence also didn't show any significant difference between the acetaminophen group and control group (OR = 0.87; 95%CI, 0.57 to 1.33). CONCLUSIONS: Perioperative intravenous acetaminophen use in multimodal analgesia could significantly reduce of total opioid consumption, but it did not contribute to decrease the average pain scores and shorten the length of hospital stays in total hip or knee arthroplasty.