As a common complication of diabetes, the incidence of diabetic peripheral neuropathy (DPN) is 60–70% worldwide. DPN is a major risk factor for diabetic foot, which may lead to foot ulceration and even amputation. The treatment of DPN remains challenging. Our preliminary study demonstrated that the external application of Tangbi Waixi (TW) decoction to the lower extremities relieved clinical symptoms and improved nerve conduction velocity in DPN patients. The aim of this study was to verify the efficacy of TW among DPN patients and evaluate the herb mixture’s safety using rigorous methodological designs. This study is a multicenter, double-blind, randomized controlled trial. A total of 640 DPN patients will be recruited and randomized to receive a foot bath with either the TW decoction or control drug. Participants will be assessed at baseline and 12 and 24 weeks after treatment. The primary outcome was the change of the Toronto Clinical Scoring System (TCSS). Secondary outcomes were nerve conduction velocity, blood glucose, blood lipids, serum inflammatory cytokines, and the European Quality of Life Five-Dimension Scale (EQ-5D) and TCM symptom scores. This multicenter, prospective, randomized clinical trial will provide valuable data regarding the efficacy and safety of foot bath treatment with TW decoction. Positive results would provide a novel treatment regimen for DPN patients. Chinese Clinical Trial Registry, ChiCTR-IOR-16009331 . Registered on 8 October 2016.

Thyroid-associated ophthalmopathy (TAO), an ordinary extrathyroid syndrome of Graves' disease (GD), is closely associated with immunity. T helper (Th) 17, Th1, and Th2 cells in Th lineages are thought to be related to the disease pathogenesis. Recently, there has been growing evidence that Th17.1 cells are involved in the development and progression of TAO. The characteristics of this pathology are similar to those of Th1 and Th17 lymphocytes, which secrete interferon (IFN)-γ and interleukin (IL)-17A. This paper reviews the potential role of the Th17.1 subgroup pathogenesis of TAO. The therapeutic effects of drugs that can modulate Th17.1 cell populations are also highlighted. Rich Th17.1 cells exist in peripheral blood and ocular tissues of patients suffering from thyroid eye disease (TED), especially those with severe or steroid-resistant TAO. The bias of Th17.1 cells to secrete cytokines partly determines the pathological outcome of TAO patients. Th17.1 cells are important in regulating fibrosis, adipocyte differentiation, and hyaluronic acid production. In summary, the Th17.1 subpopulation is essential in the onset and progression of TED, and targeting Th17.1 cell therapy may be a promising therapeutic approach.

Background. Biejiajian pill (BJJP), a classical traditional Chinese formula, has been reported that it has an effective treatment for diabetic atherosclerosis in recent years, but its underlying mechanisms remain elusive. The study aimed to explore the potential mechanisms of BJJP on diabetic atherosclerosis by integrating network pharmacology, molecular docking, and molecular dynamics simulation. Methods. The active components of BJJP were collected by TCMSP and TCMID, and then the potential targets were obtained from the SwissTargetPrediction database. The targets related to diabetic atherosclerosis were identified from the GeneCards and OMIM databases. The intersection of the potential targets regulated by active components of BJJP and the targets of diabetic atherosclerosis were common targets, which were visualized by the Venn diagram. The common targets were imported into the STRING database to construct a protein-protein interaction (PPI) network. The network of Medicine-Compound-Target was constructed with Cytoscape 3.7.1 software. GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using the DAVID database and visualized through bioinformatics. The intersecting targets were input into Cytoscape 3.7.1 software, and the Network Analyzer tool was employed to screen out the key targets. Then molecular docking was used to verify the binding affinity between the active compounds and the key targets, and molecular dynamics simulation was used to investigate the stability of the binding models. Results. A total of 81 active components, 186 targets of BJJP, and 4041 targets of diabetic atherosclerosis were obtained. Furthermore, 121 overlapping targets were identified. GO functional enrichment analysis revealed that these targets were correlated with the oxidation-reduction process, negative regulation of apoptotic process, inflammatory response, and other biological processes. The results of the KEGG pathway enrichment analysis showed that the common targets mainly participated in proteoglycans in cancer, PPAR signaling pathway, adherens junction, insulin resistance, HIF-1 signaling pathway, PI3K-Akt signaling pathway, etc. The results of molecular docking confirmed that the core active components in BJJP could bind well to the key targets. Results from molecular dynamics simulation showed that the binding energies of AKT1-Luteolin, MMP9-quercetin, and MMP9-luteolin complexes were 28.93kJmol⁻¹, 37.12kJmol⁻¹, and 62.91kJmol⁻¹, respectively. Conclusion. The study revealed that BJJP is characterized as multicomponent, multitarget, and multipathway to treat diabetic atherosclerosis, which is helpful to provide ideas and a basis for pharmacological research and clinical application in the future.

Objective. To research the efficacy of Biejiajian pill (BJJ) on diabetes-associated atherosclerosis and explore its subsequent mechanisms. Methods. Diabetes-associated atherosclerosis (AS) was established in apolipoprotein E knockout (ApoE^−/−) mice using high-fat diet and streptozotocin. Atorvastatin (ATV, 10mg/kg/day) or BJJ-L (BJJ low-dose, 0.9g/kg/day), BJJ-M (BJJ medium-dose, 1.8g/kg/day), and BJJ-H (BJJ high-dose, 3.6g/kg/day) were administered to diabetic ApoE^−/− mice for 12 continuous weeks. The normal control group consisted of 10 male C57BL/6J mice. Atherosclerosis plaques, vascular endothelial function, fasting blood glucose, lipid metabolism, inflammatory factors, NLRP3 inflammasome expression, and mitochondria and autophagy changes were evaluated. Results. The atherosclerotic lesions areas in the aortas were analyzed through Oil Red O and H&E staining, and they were reduced in the BJJ-H and BJJ-M groups. In the BJJ group, endothelin-1 (ET-1) levels were decreased, whereas endothelial nitric oxide synthase (eNOS) was increased. Fasting blood glucose levels in the BJJ and ATV groups were gradually decreased. Lipid metabolism parameters such as TG, TC, and LDL-C were reduced, while HDL-C was elevated in BJJ groups. The serum IL-1β and IL-18 were decreased under BJJ therapy. The aortic mRNA and protein expressions of NF-κB, TXNIP, NLRP3, ASC, caspase-1, and IL-1β were inhibited in BJJ-H and BJJ-M groups, especially in the BJJ-H group. Electron microscopy revealed an increase in autophagy in each treatment group. Conclusions. The findings reveal that BJJ could alleviate diabetic atherosclerosis in diabetic ApoE^−/− mice by inhibiting NLRP3 inflammasome.