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Graves’ disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune tolerance. Dipeptidyl peptidase-4 (DPP-4) is expressed on multiple immune cells. This study aimed to investigate the relationship between serum concentration/activity of DPP4 and the severity of hyperthyroidism in GD patients. A total of 82 newly diagnosed drug-naive patients with GD hyperthyroidism, 20 patients with non-autoimmune thyrotoxicosis and 122 age- and sex- matched healthy controls were enrolled. The clinical parameters and serum concentration and activity of DPP4 were measured. The GD group had increased serum concentration and activity of DPP4 than the healthy controls and patients with non-autoimmune thyrotoxicosis, while no significant difference was observed in the latter two groups. Multivariate linear regression indicated that the serum concentration/activity of DPP4 were positively associated with FT3, FT4 and TRAb levels in the GD patients. And the positive association between serum concentration/activity of DPP4 and TRAb was remained even after adjustment for confounding factors (all p < 0.05). The GD patients had significantly increased serum concentration/activity of DPP4. And the serum concentration/activity of DPP4 was positively associated with the severity of hyperthyroidism in GD patients.Key messagesThe activity and concentration of DPP4 in patients with Graves’ disease were higher than those in healthy controls.There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves’ disease.In patients with Graves ‘disease, serum DPP4 activity was positively correlated with TRAb levels. The activity and concentration of DPP4 in patients with Graves’ disease were higher than those in healthy controls. There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves’ disease. In patients with Graves ‘disease, serum DPP4 activity was positively correlated with TRAb levels.

Additional file 1: Supplementary Table S1. Mutation types of 506 patients by Sanger sequencing.

Additional file 3: Supplementary Figure S1. Examination images of case 2. (A) CT revealed an irregular mass sized 18.5×7.3×28.2 cm located in the left abdominal cavity. The margins of the lesion could not be clearly discriminated from the stomach and intestinal walls (red arrow). (B) The tumor showed an epithelioid growth pattern by H&E staining (200×). (C) The tumor cells showed a positive cytoplasmic signal for CD117 (200×). (D) The tumor cells showed a positive cytoplasmic signal for DOG1 (200×). (E) The tumor cells showed a negative cytoplasmic signal for SMA (200×). (F) ALK IHC showed positive strong and diffuse staining by the 1A4 clone (200×). (G) ALK IHC showed positive strong and diffuse staining by the D5F3 clone (200×). (H) A break-apart fluorescent in situ hybridization (FISH) assay did not reveal ALK rearrangement (1000×). Supplementary Figure 2. Examination images of case 3. (A) Preoperative CT showed a mixed slightly low-density mass of approximately 15.7×7.6 cm in the right-middle abdomen. Contrast-enhanced scanning showed uneven enhancement, with multiple areas of unenhanced necrosis (red arrow). (B) The tumor demonstrated epithelioid and spindle growth by H&E staining (200×). (C) The tumor cells showed a positive cytoplasmic signal for CD117 (200×). (D) The tumor cells showed a positive cytoplasmic signal for DOG1 (200×). (E) The tumor cells showed a negative cytoplasmic signal for SMA (200×). (F) ALK IHC showed strong positive staining by the 1A4 clone (200×). (G) ALK IHC showed strong positive staining by the D5F3 clone (200×). (H) A break-apart fluorescent in situ hybridization (FISH) assay did not identify ALK rearrangement, but some tumor cells were identified as having a copy number >2 (1000×). Supplementary Figure 3. The examination images of case 4. (A) Examination CT showed uneven enhanced density shadows in the pelvic cavity, right rectus abdominus region and deep right abdominal wall, the maximum size of which was 11.0 cm×6.7 cm (red arrow). (B) The tumor demonstrated a spindle growth pattern stained by H&E staining (200×). (C) The tumor cells showed a positive cytoplasmic signal for CD117 (200×). (D) The tumor cells showed a positive cytoplasmic signal for DOG1 (200×). (E) The tumor cells showed a positive cytoplasmic signal for SMA (200×). (F) ALK IHC showed positive staining by the 1A4 clone (200×). (G) ALK IHC showed strong positive staining by the D5F3 clone (200×). (H) A break-apart fluorescent in situ hybridization (FISH) assay did not reveal ALK rearrangement (1000×). Supplementary Figure 4. PAGE electrophoresis results of RT-PCR products of two available pairwise tissues. Lane 1-4 and 5-8 show the electrophoresis results of case 1 and case 3. Lane M, DNA marker; Lane 1/5, PCR amplification product obtained with ALK gene primers from normal tissues; Lane 2/6, PCR amplification product obtained with ALK gene primers from tumor tissues; Lane 3/7, PCR amplification product obtained with GAPDH gene primers from normal tissues; Lane 4/8, PCR amplification product obtained with GAPDH gene primers from tumor tissues.

Additional file 2: Supplementary Table S2. Demographic and clinicopathological features of ALK-positive group and ALK-negative group.

Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) and proficient DNA mismatch repair (pMMR) exhibit heterogeneous tumor characteristics, distinct responses to immunotherapy, and different survival outcomes. However, it is unclear whether gut microbiota is distinct between CRCs with different MMR status. In this study, we used immunohistochemistry for four major MMR proteins to determine the MMR status in 230 CRC patients. The gut microbiota was profiled in cancerous and adjacent normal tissues by using bacterial 16S rRNA sequencing. The differences in microbiota diversity, composition and related metabolic pathways between patients with dMMR and pMMR CRCs were explored. Linear discriminant analysis effect size (LEfSe) analysis was further applied to validate the significant taxonomic differences at the genus level. In our study cohort, dMMR status was identified in 29 of 230 (12.61%) tumors. The richness (alpha-diversity) of gut microbiome in dMMR tumor tissue was higher compared with pMMR tumor tissues. The microbial community composition (beta-diversity) between the two groups was significantly different. The dMMR group was enriched considerably for some microbiota, including Fusobacteria, Firmicutes, Verrucomicrobia, and Actinobacteria at the phylum level and Fusobacterium, Akkermansia, Bifidobacterium, Faecalibacterium, Streptococcus, and Prevotella bacteria at the genus level. However, the pMMR group was dominated by Proteobacteria at the phylum level and Serratia, Cupriavidus and Sphingobium at the genus level. Moreover, a wide variety of microbiota associated functional pathways were observed with different MMR status. KEGG pathway analysis indicated a higher abundance of the biosynthesis and metabolic pathways of glycan and nucleotide, cell growth and death pathways, genetic replication and repair pathways in dMMR samples compared with the pMMR group. These findings demonstrate that CRC patients with different MMR status have distinct gut bacterial community richness, compositions and related metabolic pathways, suggesting basis that may explain the effectiveness of immunotherapy in dMMR tumors.

Additional file 1 Supplemental Table 1. Characteristics of male participants with various levels of Lp(a). Supplemental Table 2. Characteristics of female participants with various levels of Lp(a). Supplemental Table 3. Multiple linear regression between Lp(a) levels and other parameters in male participants. Supplemental Table 4. Multiple linear regression between Lp(a) levels and other parameters in female participants.