Case report: Adult NTRK-rearranged spindle cell neoplasms with TPM3-NTRK1 fusion in the pelvic.

NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) are rare soft tissue tumor molecularly characterized by NTRK gene rearrangement, which occurs mostly in children and young adults, and rarely in adults. The abnormal tumor located in superficial or deep soft tissues of human extremities and trunk mostly, and rarely also involves abdominal organs. In this case, we report a malignant NTRK-RSCN that occurred in the pelvic region of an adult. The patient was found to have a large tumor in the pelvic region with a pathological diagnosis of infiltrative growth of short spindle-shaped tumor cells with marked heterogeneity. Immunohistochemistry of this patient showed positive vimentin, pan-TRK and Ki67 (approximately 60%) indicators with negative S100, Desmin and DOG1. Molecular diagnosis revealed c-KIT and PDGFRα wild type with TPM3-NTRK1 fusion, unfortunately this patient had a rapidly progressive disease and passed away. This case highlights the gene mutation in the molecular characteristics of NTRK-RSCNs, and the significance of accurate molecular typing for the diagnosis of difficult cases.

Evidence for the gut-skin axis: Common genetic structures in inflammatory bowel disease and psoriasis.

BACKGROUND: Inflammatory bowel disease (IBD) and psoriasis (Ps) are common immune-mediated diseases that exhibit clinical comorbidity, possibly due to a common genetic structure. However, the exact mechanism remains unknown. METHODS: The study population consisted of IBD and Ps genome-wide association study (GWAS) data. Genetic correlations were first evaluated. Then, the overall evaluation employed LD score regression (LDSC), while the local assessment utilized heritability estimation from summary statistics (HESS). Causality assessment was conducted through two-sample Mendelian randomization (2SMR), and genetic overlap analysis utilized the conditional false discovery rate/conjunctional FDR (cond/conjFDR) method. Finally, LDSC applied to specifically expressed genes (LDSC-SEG) was performed at the tissue level. For IBD and Ps-specific expressed genes, genetic correlation, causality, shared genetics, and trait-specific associated tissues were methodically examined. RESULTS: At the genomic level, both overall and local genetic correlations were found between IBD and Ps. MR analysis indicated a positive causal relationship between Ps and IBD. The conjFDR analysis with a threshold of < 0.01 identified 43 loci shared between IBD and Ps. Subsequent investigations into disease-associated tissues indicated a close association of IBD and Ps with whole blood, lung, spleen, and EBV-transformed lymphocytes. CONCLUSION: The current research offers a novel perspective on the association between IBD and Ps. It contributes to an enhanced comprehension of the genetic structure and mechanisms of comorbidities in both diseases.

Genetically predicted levels of circulating cytokines and the risk of six immune skin diseases: a two-sample Mendelian randomization study.

Background: Circulating cytokines play a crucial role in the onset and progression of immune skin diseases. However, the causal relationships and the direction of causal effects require further investigation. Methods: Two-sample Mendelian randomization (MR) analyses were conducted to assess the causal relationships between 41 circulating cytokines and six immune skin diseases including alopecia areata, chloasma, hidradenitis suppurativa (HS), lichen planus (LP), seborrheic dermatitis, and urticaria, using summary statistics from genome-wide association studies. Reverse MR analyses was performed to test for the reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Results: Twelve unique cytokines showed a suggestive causal relationship with the risk of six immune skin diseases. Among them, the causal effects between 9 unique cytokines and immune skin diseases have strong statistical power. Additionally, the concentrations of six cytokines might be influenced by LP and urticaria. After Bonferroni correction, the following associations remained significant: the causal effect of beta-nerve growth factor on HS (odds ratio [OR] = 1.634, 95% confidence interval [CI] = 1.226-2.177, p = 7.97e-04), interleukin (IL)-6 on LP (OR = 0.615, 95% CI = 0.481-0.786, p = 1.04e-04), IL-4 on LP (OR = 1.099. 95% CI = 1.020-1.184, p = 1.26e-02), and IL-2 on urticaria (OR = 0.712, 95% CI = 0.531-0.955, p = 2.33e-02). Conclusion: This study provides novel perspectives on the relationship between circulating cytokines and immune skin diseases, potentially providing valuable insights into their etiology, diagnostic approaches, and treatment.

Gut microbiota and acne: A Mendelian randomization study.

BACKGROUND: Prior observational studies have identified a relationship between the composition of gut microbiota and the onset of acne. To ascertain the causal relationship underlying this association, we adopted the Mendelian randomization (MR) method, which offers a powerful approach to causal inference. METHODS: Summary statistics on gut microbiota and acne were obtained from the MiBioGen and FinnGen consortium, respectively. The causal relationship was assessed using multiple methods in a two-sample framework, including MR Egger, weighted median, inverse variance weighted (IVW), and weighted mode. Furthermore, the heterogeneity and horizontal pleiotropy analyses were conducted, along with the leave-one-out method. RESULTS: The IVW estimation indicated that Allisonella (odds ratio [OR] = 1.42, 95% confidence interval [CI] = 1.18-1.70, p = 0.0002) and Bacteroides (OR = 2.25, 95% CI = 1.48-3.42, p = 0.0001) have adverse effects on acne. By contrast, Ruminococcus torques group (OR = 0.41, 95% CI = 0.25-0.65, p = 0.0002) showed a beneficial effect on acne. In addition, Candidatus soleaferrea (OR = 0.75, 95% CI = 0.60-0.95, p = 0.0149), Eubacterium coprostanoligenes group (OR = 0.67, 95% CI = 0.47-0.95, p = 0.0230), Fusicatenibacter (OR = 0.71, 95% CI = 0.52-0.97, p = 0.02897), and Lactobacillus (OR = 0.72, 95% CI = 0.58-0.90, p = 0.0046) showed suggestive associations with acne. CONCLUSION: The present investigation suggests a causal effect of gut microbiota on acne.

Anal fistulotomy with one-stage shaped skin grafting for intersphincter anal fistulas: study protocol on a multicentre randomised controlled trial.

BACKGROUND: Anal fistulas are mainly treated via surgery. They can be difficult to treat without surgical intervention. Numerous procedures, such as fistulectomy and fistulotomy, are performed to treat anal fistulas and achieve good effects. However, the wounds created through fistulectomy and fistulotomy take a long time to heal. Therefore, a multicentre randomised controlled trial (RCT) is proposed to study the efficacy of one-stage shaped skin grafting at the surgical wound to heal low simple intersphincter anal fistulas. METHODS: This study is a multicentre, hospital-based RCT. It will be performed at three hospitals. A total of 104 patients with low simple intersphincter anal fistulas who meet the inclusion criteria will be included in this trial and will be allocated randomly to two groups (test and control groups). The patients in the test group will receive one-stage anal fistulotomy surgery combined with shaped skin grafting, and those in the control group will undergo anal fistulotomy only. All the operations will be performed by attending colorectal surgeons or surgeons of a higher level. Effectiveness and safety indicators will be observed, recorded and analysed. DISCUSSION: Anal fistulotomy can heal low simple intersphincter anal fistulas effectively and safely with a low recurrence rate. Skin grafts promote wound epithelisation significantly. We believe that skin grafting can treat low simple intersphincter fistulas with a short healing time. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000039174. Registered on 28 October 2020.