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There is a lack of certain evidence for the therapeutic efficacy of probiotics for adult atopic dermatitis (AD). PubMed, EMBASE, and the Cochrane Database were searched for relevant studies, and randomized controlled trials of AD describing treatment with single/mixed probiotic therapy were included. Changes in outcomes were calculated by standard mean difference (SMD) and 95% confidence interval (CI). Relative efficacies of the probiotics were ranked by the surface under the cumulative ranking (SUCRA). Nine studies with a total of 402 participants, including 208 AD patients who received probiotic treatments and 194 controls, were considered during the current analysis. A reduction in disease severity for probiotic supplementation compared to controls in both the short term (SMD: 0.63; 95% CI: 0.02–1.25) and the long term (SMD: 1.57; 95% CI: 0.66–2.49). There was a significant improvement in long-term quality of life after probiotic supplementation compared with controls (SMD: 0.74; 95% CI: 0.39–1.09). A mixture of L. salivarius (LS01) and Bifidobacterium (BR03) was found the highest probability of the best supplementation. Probiotic supplementation decreases clinical severity and improves the quality of life among adult AD patients. The mixture of LS01 and BR03 appeared optimal. [ABSTRACT FROM AUTHOR]

Backgrounds. Polysaccharides of Dendrobium candidum (PDC) showed a strong antioxidant effect on islet cells while the effects of PDC on human umbilical vein endothelial cells (HUVECs) under the high glucose condition remain unclear. Material and Method. HUVECs were incubated with high glucose (33.3 mmol/L) for 48 hours to induce injury, and cells were treated with PDC (100, 200, and 400 μg/mL) for 48 hours. The tetrazolium blue colorimetric (MTT) assay was used to detect cell proliferation, superoxide dismutase (SOD), and nitric oxide (NO) content in cell supernatants. Flow cytometry was used to detect reactive oxygen species (ROS) and calcium levels. Results. (1) Compared with the control group, the proliferation of HUVECs cells in the high glucose (33.3 mmol/L) group decreased (P < 0.05). The intracellular calcium ion concentration and the intracellular ROS level increased (P < 0.01 and P < 0.05). SOD activity and the level of NO in the culture medium were reduced (P <0.05). (2) Compared with the control group, PDC (50, 100, 200, 400, and 800 μg/mL) did not significantly affect the cell proliferation of HUVECs (P > 0.05). (3) Compared with the high glucose group, the HUVEC cell viability of the high glucose + PDC (100, 200, and 400 μg/mL) group increased while the intracellular calcium ion concentration decreased in a concentration-dependent manner (P < 0.05). Intracellular ROS levels were reduced, while SOD activity and the level of NO in culture fluids increased (P < 0.05). Conclusion. PDC can promote the proliferation of HUVECs in the high glucose environment by reducing oxidative stress injury of HUVECs induced by high glucose. [ABSTRACT FROM AUTHOR]

Background: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework. Methods: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications. Results: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR. Conclusion: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]

The effects of Dendrobium polysaccharides (PDC) on the functions of human skin fibroblasts (HSFs) and expression of matrix metalloproteinase-2 under high-glucose conditions and exploration of the underlying mechanism remain unclear. We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis and flow cytometry to evaluate the cell viability and apoptosis. The collagen levels were determined by the Sircol™ Collagen Assay. Real-time quantitative polymerase chain reaction (RT-PCR) was used to detect the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase inhibitor (TIMP-2) mRNA. We found the following: (1) under the high-glucose condition, the HSF cell viability, the expression of TIMP-2 mRNA, and the collagen levels were reduced, while the apoptosis rate and the expression of MMP-2 mRNA increased (P < 0.05). (2) In the high-glucose + PDC group, the PDC reversed the changes in the collagen level, viability, and apoptosis rate of the HSF cells caused by high glucose, with the expression of protein and TIMP-2 mRNA increased and the level of MMP-2 mRNA decreased (P < 0.05). This is the first time attempting to reveal that PDC can exhibit protective effects on HSF under high-glucose conditions, which may be related to the upregulation of the TIMP-2 expression and inhibition of the MMP-2 expression. [ABSTRACT FROM AUTHOR]

Objective. Osteoarthritis (OA) is the most common degenerative joint disease, causing joint pain, stiffness, and even disability. Guidelines recommend intra-articular injections as an alternative treatment to relieve OA symptoms for patients who demonstrate poor tolerability or compliance to oral administration of drugs. Mesenchymal stem cells (MSCs) are a potential treatment for of OA. We conducted this network meta-analysis to comprehensively compare the efficacy and safety between hyaluronic acid (HA), corticosteroids (GCs), platelet-rich plasma (PRP), and MSCs. Design. Systematic review and Bayesian network meta-analysis. Data Sources. Relevant studies, published from January 2000 to January 2020, in the PubMed, Cochrane library, EMBASE, and CKNI databases. Methods. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement, improvement in joint stiffness, and risk of adverse effects (AEs) were assessed. Results. Twenty-five articles with 4642 patients were included. Overall, MSC therapy was the most effective treatment for pain relief (standardized mean difference compared with placebo = 3.61 , 95% CI [1.87 to 5.35]). Both MSC and PRP therapies improved every symptom of OA effectively and have an advantage over HA and GCs which are recommended by guidelines. MSCs, PRP, HA, and GCs are tolerated well for patients in long-term treatment of OA compared with placebo. Conclusions. The results show that MSCs relieve pain, stiffness, and dysfunction due to OA better than PRP, HA, and GCs and are not statistically correlated with greater safety concerns. More high-quality trials are needed to reconfirm the findings of this study, however, standardization of preparation of MSCs and PRP should be investigated in the future. [ABSTRACT FROM AUTHOR]

Objective. Most guidelines recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol for the nonoperative treatment of osteoarthritis (OA), but the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti–IL-1α/β dual variable domain immunoglobulin that can simultaneously bind and inhibit IL-1α and IL-1β to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines. Methods. We conducted a Bayesian network and conventional meta-analyses to compare the efficacy and safety of lutikizumab with other traditional drugs. All eligible randomized clinical trials, in PubMed, CNKI, EMBASE, and Web of Science databases, from January 2000 to January 2020, were included. The Cochrane risk of the bias assessment tool was used for quality assessment. Pain relief, function improvement, and risk of adverse effects (AEs) were compared in this study. Results. 24 articles with 11858 patients were included. Duloxetine (DUL) had the largest effect for pain relief (4.76, 95% CI [2.35 to 7.17]), and selective cox-2 inhibitors (SCI) were the most efficacious treatment for physical function improvement (SMD 3.94, 95% CI [2.48 to 5.40]). Lutikizumab showed no benefit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in the treatment of OA compared with placebo. Conclusions. Lutikizumab, the new anti–Interleukin-1α/β dual variable domain immunoglobulin, showed no improvement in pain or function when compared with placebo. Selective cox-2 inhibitors and duloxetine remain the most effective and safest treatment for OA. More high-quality trials are still needed to reconfirm the findings of this study. [ABSTRACT FROM AUTHOR]

Purpose. Previous studies confirmed that chronic arsenic exposure could lead to pigmentary changes and hyperkeratosis. However, skin health-related quality of life (HRQoL) among people under lifetime arsenic exposure remains underappreciated. Our study is aimed at investigating several patient-reported outcomes in a population under chronic arsenic exposure. Patients and Methods. A cross-sectional study was conducted in communities in Shimen, China. Dermatologists performed skin examinations for participants. Patient-reported outcomes (PROs) included HRQoL, itch, sleep quality, and symptoms of anxiety and depression. The Dermatology Life Quality Index (DLQI) was used to measure skin HRQoL. The numerical rating scale (NRS) was used to measure the intensity of itching. Sleep disturbance was measured by Pittsburgh Sleep Quality Index (PSQI). Anxiety and depression were measured by two-item Generalized Anxiety Disorder (GAD-2) and Patient Health Questionnaire (PHQ-2), respectively. Results. A total of 464 participants suffering from arsenic-related skin lesions finished the assessment of DLQI. Pigmentary changes and arsenical keratosis were not associated with the patient-reported outcomes except PHQ-2. Hair arsenic exceeding 1 μg/g was associated with higher itch NRS and DLQI (P < 0.05). Itch NRS (adjusted β = 0.80 , 95% CI: 0.70–0.90, P < 0.01) and hair arsenic concentration (adjusted β = 0.12 , 95% CI: 0.01–0.24, P < 0.05) were independently associated with the DLQI. Conclusion. HRQoL, sleep quality, and mental wellbeing are impaired in residents under chronic arsenic exposure. Itching and hair arsenic are independent risk factors for impaired HRQoL. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of emodin on nitric oxide (NO) secretion induced by high glucose in human umbilical vein endothelial cells (HUVECs) through the p-Akt signaling pathway. Methods. Sensitivity of cells to emodin was determined by MTT assay to establish the experimental concentrations; then, HUVECs were treated with high-dose (33.3 mmol/L) glucose (HG), HG + emodin (HG + E), HG + the Akt phosphorylation inhibitor LY294002 (HG + LY), or HG + E + LY. The p-Akt (Ser 473) expression in 48 h was analyzed using Western blot. NO effect on the secretion of HUVECs was analyzed using nitrate reductase assay. Results. The sensitive emodin concentration for HUVECs growth was 10 mol/L (P < 0.05). Compared with the HG group, NO secretion was significantly higher in the HG + E group (P < 0.05), whereas it was lowest in the HG + LY group (P < 0.05). Compared with the HG + LY group, NO secretion was increased in the HG + E + LY group (P < 0.05). The p-Akt protein expression was decreased in the HG + LY group when compared to the HG group (P < 0.05), while it significantly increased in the HG + E group (P < 0.05). Compared with HG + LY group, p-Akt protein expression was significantly higher in the HG + E + LY group (P < 0.05). Conclusion. Emodin could improve the NO secretion of HUVECs by high glucose through the p-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Objective. To investigate the effects of emodin on nitric oxide (NO) secretion induced by high glucose in human umbilical vein endothelial cells (HUVECs) through the p-Akt signaling pathway. Methods. Sensitivity of cells to emodin was determined by MTT assay to establish the experimental concentrations; then, HUVECs were treated with high-dose (33.3 mmol/L) glucose (HG), HG + emodin (HG + E), HG + the Akt phosphorylation inhibitor LY294002 (HG + LY), or HG + E + LY. The p-Akt (Ser 473) expression in 48 h was analyzed using Western blot. NO effect on the secretion of HUVECs was analyzed using nitrate reductase assay. Results. The sensitive emodin concentration for HUVECs growth was 10 mol/L (P < 0.05). Compared with the HG group, NO secretion was significantly higher in the HG + E group (P < 0.05), whereas it was lowest in the HG + LY group (P < 0.05). Compared with the HG + LY group, NO secretion was increased in the HG + E + LY group (P < 0.05). The p-Akt protein expression was decreased in the HG + LY group when compared to the HG group (P < 0.05), while it significantly increased in the HG + E group (P < 0.05). Compared with HG + LY group, p-Akt protein expression was significantly higher in the HG + E + LY group (P < 0.05). Conclusion. Emodin could improve the NO secretion of HUVECs by high glucose through the p-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Observational research reported the underlying correlation of metabolic syndrome (MetS) and its components with rotator cuff tendinopathy (RCT), but their causality remained unclear. This study aimed to investigate whether genetically predicted MetS was related to the risk of RCT. Methods: Both univariable and multivariable Mendelian randomization (MR) analysis was applied using summary-level data from the most comprehensive genome-wide association studies to estimate the associations of MetS and its component with RCT, with the inverse variance weighted (IVW) as the primary method, and the method of Causal Analysis Using Summary Effect Estimates (CAUSE) as a supplement for false positives detection. The mediation analysis was furtherly used for the assessment of direct and indirect effects. Results: Univariable analysis revealed that genetically predicted MetS (OR: 1.0793; 95% CI 1.0311 to 1.1297), body mass index (BMI) (OR 1.2239; 95% CI 1.1357 to 1.3189), and waist circumference (WAC) (OR 1.3177; 95% CI 1.2015 to 1.4451) had a significant positive association with the risk of RCT. Triglycerides and systolic blood pressure were suggestively associated with RCT risk. These associations were also identified by CAUSE. There was independent causality of BMI (OR: 1.1806; 95% CI 1.0788 to 1.2920) and WAC (OR 1.3716; 95% CI 1.2076 to 1.5580) on RCT after adjustment for confounders. No mediator was found in the causal associations. Conclusion: Our study revealed the genetic causality of MetS and its components, especially BMI and WAC, with RCT risk. Early prevention and diagnosis of excess central adiposity contributing to MetS are significant in the RCT risk management. [ABSTRACT FROM AUTHOR]

Background. As a pathological process, osteonecrosis of the femoral head (ONFH) is characterized by the avascularity of the femoral head, cellular necrosis, microfracture, and the collapse of the articular surface. Currently, critical treatment for early-stage ONFH is limited to core decompression. However, the efficacy of core decompression remains controversial. To improve the core decompression efficacy, regenerative techniques such as the use of platelet-rich plasma (PRP) were proposed for early-stage ONFH. As a type of autologous plasma containing concentrations of platelets greater than the baseline, PRP plays an important role in tissue repair, regeneration, and the differentiation of mesenchymal stem cells (MSCs). In this review, we present a comprehensive overview of the operation modes, mechanism, and efficacy of PRP for early-stage ONFH treatment. Methods. We searched for relevant studies in the PubMed, Web of Science, and Embase databases. By searching these electronic databases, the identification of either clinical or experimental studies evaluating PRP, MSC, core decompression, and ONFH was our goal. Results. Seventeen studies of PRP and avascular necrosis of the femoral head were evaluated in our review. Ten studies related to the possible mechanism of PRP for treating ONFH were reviewed. Seven studies of the operation modes of PRP in treating ONFH were identified. We reviewed the efficacy of PRP in treating ONFH systematically and made an attempt to compare the PRP operation modes in 7 studies and other operation modes in past studies for early-stage ONFH treatment. Conclusion. PRP treats ONFH mainly through three mechanisms: inducing angiogenesis and osteogenesis to accelerate bone healing, inhibiting inflammatory reactions in necrotic lesions, and preventing apoptosis induced by glucocorticoids. In addition, as an adjunctive therapy for core decompression, the use of PRP is recommended to improve the treatment of early-stage ONFH patients, especially when combined with stem cells and bone grafts, by inducing osteogenic activity and stimulating the differentiation of stem cells in necrotic lesions. [ABSTRACT FROM AUTHOR]

Background. Ankylosing spondylitis (AS) is a common immune-related systemic chronic inflammatory osteoarthropathy. Previous studies have proven that biologic agents, including IL-17A inhibitors (IL17Ai), TNF-α inhibitor FC fusion protein (TNFiFCP), or fully human monoclonal antibody (TNFiNMA) and JAK inhibitor (JAKi), are effective for AS treatment. Our study is aimed at comparing the clinical efficacy, tolerability, and safety of different biological agents, including novel IL-6 inhibitor (IL6i), IL-23 inhibitor (IL23i), and IL-17 A/F dual variable domain inhibitor (IL17AFi) in AS. Method. PubMed, Scopus, Embase, CNKI, and the Cochrane Library were systematically searched. A frequentist framework network meta-analysis with a random-effects model was performed. Ranking effects were calculated by surface under the cumulative ranking analysis (SUCRA) and cluster-rank analysis. Results. IL17AFi reported both the highest ASAS40 (SUCRA = 91.4 %) and ASAS20 (SUCRA = 92.5 %) response, while IL6i and IL23i reported the lowest responses (SUCRA = 6.6 % and 19.9%, respectively). With the exceptions of IL6i (RR 0.60, 95% CI (0.22 to 1.67) for ASAS40 and 1.36 (0.71 to 2.58) for ASAS20) and IL23i (0.98 (0.68 to 1.40) for ASAS40 and 0.91 (0.70 to 1.19) for ASAS20), all biological drugs demonstrated statistically superior ASAS responses than placebo. TNFiFMA performed best in the suppression of disease activity (SUCRA = 77.4 %, SMD 2.35, and 95% CI (1.11 to 3.59)) and functional improvement (SUCRA = 68.8 %, SMD 1.67, and 95% CI (0.59 to 2.74)). There were no significant differences in tolerability or safety between biologic drugs and placebo. Conclusions. The novel IL-17 A/F dual variable domain inhibitor, bimekizumab, may be an ideal future treatment choice for AS, while IL-23 and IL-6 inhibitors demonstrate little potential in the treatment of AS. For patients with rapid disease progression and severe functional limitation, TNF-α inhibitors, especially infliximab, are safe and effective and could be a first-line treatment choice. [ABSTRACT FROM AUTHOR]

A highly sensitive nonenzymetic glucose electrochemical electrode was fabricated by an efficient multicomponent hierarchical structure, which is constructed by integrating the nickel cobalt layered double hydroxide (NiCo-LDH) and cobalt copper carbonate hydroxide (CCCH) hierarchical nanostructure on Cu foam (NiCo-LDH/CCCH/CuF). Then, a glucose sensing system was developed by interfacing the NiCo-LDH/CCCH/CuF electrode to the as-prepared custom-printed circuit board (PCB) with potentiostat function. • A nonenzymetic glucose sensor was developed based on multicomponent hierarchical NiCo-LDH/CCCH/CuF nanostructures. • The Ni:Co mole ratio and synthesis time of NiCo-LDH nanosheets were optimized toward glucose detection. • The NiCo-LDH/CCCH/CuF sensor exhibits high sensitivity, low detection limit and fast response time for glucose analyses. • The sensing system was realized by integrating NiCo-LDH/CCCH/CuF electrode with PCB for micromole level glucose detection. A highly sensitive nonenzymetic electrochemical glucose sensor was developed by using a multicomponent sensing electrode made of nickel cobalt layered double hydroxide (NiCo-LDH) and cobalt copper carbonate hydroxide (CCCH) hierarchical nanostructure on Cu foam (NiCo-LDH/CCCH/CuF). The results of electrochemical measurements show that both the large accessible surface area of hierarchical nanostructure and the good conductivity of Cu foam are in favor of electrocatalysis so that the glucose detection. We have systematically evaluated the catalytic performance of NiCo-LDH/CCCH/CuF systems by changing the Ni:Co mole ratio and the synthesis time based on both cyclic voltammetry and amperometry techniques. Our results indicate that the optimization NiCo-LDH/CCCH/CuF system exhibits high sensitivity (10.78 μA/μM/cm2), large linear concentration range (0.001 1.5 mM) and fast response-recovery times (2.4 s and 2.0 s) for glucose analyses. By integrating the NiCo-LDH/CCCH/CuF glucose sensing electrode with the custom-printed circuit board (PCB), we also demonstrate the feasibility of glucose detection at micromole level. Therefore, the NiCo-LDH/CCCH/CuF hierarchical nanostructure is applicable to the high sensitivity glucose determination. [ABSTRACT FROM AUTHOR]