Efficacy of Chinese medicine in the adjuvant treatment of Hashimoto's thyroiditis with hypothyroidism: a systematic review and meta-analysis.

The quality of the studies was assessed using the Cochrane risk bias assessment tool and the results were analyzed using Review Manager 5.3 software. The evidence was also evaluated for its strength using GRADE. A total of 18 randomized controlled trials were included in the study, involving 1247 patients. The primary outcomes of this study included overall efficacy, effectiveness in treating specific symptoms, and the Traditional Chinese Medicine symptom score. The secondary outcomes included the levels of FT3, FT4, and TSH, the size of the thyroid gland, and any adverse events. The results of the meta-analysis showed that CHM combined with WM has a better curative effect and a more effective reduction in clinical symptoms than WM alone: comprehensive efficacy [OR = 4.83; 95% CI (3.45, 6.76)], syndrome efficacy [OR = 5.95; 95% CI (3.94, 8.99)], TCM symptom score SMD = -1.49; 95% CI (-1.86, -1.11)], FT3 [SMD = 0.59; 95% CI (0.48, 0.71)], FT4 [SMD = 0.59; 95% CI (0.48, 0.71)], TSH SMD = -0.97; 95% CI (-1.35, -0.58)], and thyroid volume SMD = -0.25; 95% CI (-0.34, 0.15)]. The incidence of adverse events between the groups was not significantly different [OR = 1.00; 95% CI (0.14, 7.27)]. Because of the effectiveness of CHM, we support using CHM to improve clinical efficacy in the treatment of HTH. The results of our research suggest that the use of Chinese Herbal Medicine (CHM) in combination with Western Medicine (WM) may result in improved clinical efficacy in the treatment of hypothyroidism (HTH) compared to using WM alone.

Molecular mechanism of Sishen pills in the treatment of diarrheal diabetic enteropathy based on network pharmacology.

This study aimed to explore the effectiveness and safety of Sishen pills for the treatment of diarrheal diabetic enteropathy (DDE). The Traditional Chinese Medicine (TCM) Systems Pharmacology and BATMAN-TCM databases were used to determine the chemical composition of Sishen pills and thus predict information on protein targets. We searched for potential targets of DDE in the GeneCards, DrugBank, Therapeutic Target (TTD), and DisGeNET databases. Using the intersection of the drug and disease targets, protein-protein interaction (PPI) networks and molecular interaction modules were constructed, and key targets were screened. The intersecting gene targets were imported into the Metascape database to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The core targets and active ingredients were then docked at the molecular level. Sishen pills contain 70 active ingredients, 463 targets, and 566 disease targets. A module analysis of the targets revealed that the module was mainly related to adrenergic receptor activity, the adenosine phosphate kinase signaling pathway, and the G protein-coupled receptor signaling pathway. The GO and KEGG pathway enrichment results indicated that the protein genes regulated by Sishen pills were mainly enriched in the response to lipopolysaccharides, the AMPK signaling pathway, the JAK-STAT signaling pathway, and other signaling pathways. The molecular docking results showed that the core active compounds exhibited good binding activity with the predicted targets. Sishen pills can regulate the immune function of the body through anti-inflammatory and antibacterial effects for the treatment of DDE.

The changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020.

BACKGROUND: In recent years, new drug development on lung cancer is in full swing in China. The aim of this study was to overview the changing landscape of anti-lung cancer drug clinical trials in mainland China from 2005 to 2020. METHODS: We analysed anti-lung cancer drug clinical trials registered on three websites including the China National Medical Products Administration Centre for Drug Evaluation platform, the Chinese Clinical Trial Registry and ClinicalTrials.gov. FINDINGS: A total of 1595 anti-lung cancer drug clinical trials from Jan 1st, 2005 to Dec 31st, 2020 were extracted, which included 630 (39•5%) investigator-initiated trials (IITs), 698 (43•8%) domestic industry-sponsored trials (ISTs), and 267 (16•7%) international ISTs. During the past 16 years, the number of anti-lung cancer clinical trials including IITs and domestic ISTs had a remarkable growth, however, the number of international ISTs increased slowly. The number of principal clinical trial units also increased significantly over time. Of the 1595 trials, the largest growth was observed in phase I trials during 2013-2020, with an average annual growth rate of 38•6%. 278 trials were led by principal investigators (PI) from Guangdong, followed by Beijing (n=273) and Shanghai (n=257). Among the 965 ISTs, clinical trials involving targeted drugs (588, 60•9%) accounted for the largest proportion, followed by immunotherapeutic drugs (284, 29•4%), cytotoxic drugs (75, 7•8%), and traditional Chinese medicine (18, 1•9%). In terms of targeted drugs, EGFR-TKIs remained the most studied drugs (225/588, 38•27%). As for immunotherapy, 125 out of 284 (44•01%) trials involved PD-1 inhibitors, 60 (21•13%) trials involved PD-L1 inhibitors, and seven (2•46%) trials involved CTLA-4 inhibitors. INTERPRETATION: In the past 16 years, the development of anti-lung cancer drug clinical trials has achieved much progress in mainland China. The most progress lied in targeted therapy and immunotherapy. FUNDING: This work was financially supported in part by China National Major Project for New Drug Innovation (2017ZX09304015) and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001).

Meta-analysis of the prognostic and clinical value of serum 25-hydroxyvitamin D levels in previously untreated lymphoma.

Background: This meta-analysis explored the prognostic and clinical value of serum 25-hydroxyvitamin D, 25(OH)D, levels in previously untreated lymphoma. Materials & methods: PubMed, Web of Science, Embase and the Cochrane Central Register of Controlled Trials databases were searched for eligible studies. Summary effect estimates and 95% CIs were pooled using random-effects or fixed-effects models. Results: Twelve studies with 4139 patients were included. Low level of serum 25(OH)D was associated with inferior progression-free survival (hazard ratio [HR]: 2.06; 95% CI: 1.82-2.32) and overall survival (HR: 1.94; 95% CI: 1.71-2.19), advanced disease (odds ratio [OR]: 1.52; 95% CI: 1.09-2.13) and elevated lactate dehydrogenase (OR: 1.84; 95% CI: 1.08-3.15). Conclusions: Low level of serum 25(OH)D is a prognostic risk factor for newly diagnosed lymphoma.

Lay abstract Vitamin D is a nutrient. Vitamin D deficiency is common in lymphoma patients. Serum level of 25-hydroxyvitamin D, 25(OH)D, reflects vitamin D status. Aim: We studied whether low levels of 25(OH)D are related with poor survival for newly diagnosed lymphoma. Materials & methods: We researched four databases for eligible studies. We then extracted data from the studies. Finally, we pooled the effect sizes based on the data. Results: Twelve studies with 4139 patients were included in the study. Results showed that low levels of serum 25(OH)D were associated with greater lymphoma progression and death. Patients with low serum 25(OH)D were likely to have poor clinical features as well. Conclusions: Low serum 25(OH)D is a risk factor for lymphoma survival. Assessment of vitamin D status should be considered in clinical practice. Further research is needed to assess the effect of vitamin D supplementation therapy.

Cannabinoid Receptor 2 Agonist Prevents Local and Systemic Inflammatory Bone Destruction in Rheumatoid Arthritis.

Cannabinoid receptor 2 (CB2) has been implicated as an important clinical regulator of inflammation and malignant osteolysis. Here, we observed that CB2 expression was markedly higher in the collagen-induced arthritis (CIA) mice synovium and bone tissues than in the noninflamed synovium and bone tissues. The CB2 selective agonist (JWH133) but not antagonist (SR144528) suppressed CIA in mice without toxic effects, as demonstrated by the decreased synovial hyperplasia, inflammatory responses, cartilage damage, and periarticular and systemic bone destruction. JWH133 treatment decreased the infiltration of pro-inflammatory M1-like macrophages and repolarized macrophages from the M1 to M2 phenotype. Similarly, activation of CB2 increased the expression of anti-inflammatory cytokine interleukin (IL)-10 and reduced the expression of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6. In addition, JWH133 treatment attenuated osteoclast formation and osteoclastic bone resorption, and reduced the expression of receptor activators of the nuclear factor-κB (NF-κB) ligand (RANKL), matrix metallopeptidase-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and nuclear factor of activated T-cells 1 (NFAT-1) in CIA mice and osteoclast precursors, which were obviously blocked by pretreatment with SR144528. Mechanistically, JWH133 inhibited RANKL-induced NF-κB activation in the osteoclast precursors. We found that JWH133 ameliorates pathologic bone destruction in CIA mice via the inhibition of osteoclastogenesis and modulation of inflammatory responses, thereby highlighting its potential as a treatment for human rheumatoid arthritis. © 2018 American Society for Bone and Mineral Research.

Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt/ß-catenin signaling pathway in vivo and in vitro.

Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical condition following total joint arthroplasty, which can cause implant instability and failure. The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in vivo. Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Here, we demonstrated that icariin significantly attenuated titanium-particle inhibition of osteogenic differentiation of mesenchymal stem cells (MSCs). Additionally, icariin increased bone mass and decreased bone loss in titanium-particle-induced osteolytic sites. Mechanistically, icariin inhibited decreased ß-catenin stability induced by titanium particles in vivo and in vitro. To confirm icariin mediated its bone-protective effects via the Wnt/ß-catenin signaling pathway, we demonstrated that ICG-001, a selective Wnt/ß-catenin inhibitor, attenuated the effects of icariin on MSC mineralization in vitro and bone formation in vivo. Therefore, icariin could induce osteogenic differentiation of MSCs and promote new bone formation at a titanium-particle-induced osteolytic site via activation of the Wnt/ß-catenin signaling pathway. These results further support the protective effects of icariin on particle-induced bone loss and provide novel mechanistic insights into the recognized bone-anabolic effects of icariin and an evidence-based rationale for its use in PIO treatment.

AIRE recruits multiple transcriptional components to specific genomic regions through tethering to nuclear matrix.

Thymic selection requires that diverse self antigens be presented to developing thymocytes by stromal cells. Consistent with this function, medullary thymic epithelial cells have been shown to express a large number of genes, many of which are tissue restricted. Autoimmune regulator (AIRE) is a nuclear protein, which has recently been identified as a regulator of this process, however, the mechanism by which AIRE functions is not well understood. Here we use a transrepression assay to demonstrate that AIRE interacts with multiple components of the transcription complex including a novel interaction with the UBA domain protein, GBDR1. When AIRE is expressed in cultured human thymic epithelial cells, it tightly associates with nuclear matrix, suggesting that AIRE responsive genes may be localized to specific regions. Using a mathematical approach we have re-analyzed an Affymetrix dataset identifying AIRE responsive genes and show that they tend to localize to specific regions of the genome. Together, these data suggest that AIRE regulates gene expression by recruiting components of the transcription complex to specific regions of the genome via interactions with nuclear matrix.