Precision Clinical Medicine最新文献

Background: Numerous investigations have revealed the interplay between gut microbiota (GM) and psoriasis (Ps) and psoriatic arthritis (PsA). However, the causal relationship between them remains unknown.

Methods: We curated a collection of genetic variants (P < 1 × 10^-5) associated with GM (n = 18 340) derived from the MiBioGen study. To explore the intricate relationship between GM and Ps as well as PsA, we harnessed the comprehensive resources of the FinnGen database, encompassing a vast cohort of individuals, including 4510 Ps cases and 212 242 controls and 1637 PsA cases and 212 242 controls. Mendelian randomization (MR) was used, including an inverse variance weighting method, followed by a sensitivity analysis to verify the robustness of the results.

Results: For Ps, some bacterial taxa, including Lactococcus, Ruminiclostridium 5, and Eubacterium fissicatena, were identified as risk factors; but Odoribacter demonstrated a protective effect against Ps. In the case of PsA, Lactococcus, Verrucomicrobiales, Akkermansia, Coprococcus 1, and Verrucomicrobiaceae were identified as risk factors; Odoribacter and Rikenellaceae exhibited a protective effect against the development of PsA.

Conclusion: Our study establishes a causal link between the GM and Ps and PsA. These findings provide insights into the underlying mechanisms and suggest potential therapeutic targets.

Objectives: To investigate the characteristics and prognostic value of fecal lactoferrin trajectories in ulcerative colitis (UC).

Methods: This study used data from the UNIFI trial (ClinicalTrials.gov, NCT02407236) and included patients who received ustekinumab during induction for trajectory modeling (n = 637). Patients who received ustekinumab during maintenance therapy were used for 1-year outcome analyses (n = 403). The levels of fecal lactoferrin, fecal calprotectin, and serum C-reactive protein were measured at weeks 0, 2, 4, and 8. The trajectories of these biomarkers were developed using a latent class growth mixed model.

Results: The trajectories of fecal lactoferrin, fecal calprotectin, and serum C-reactive protein were distinct, but all were associated with prior exposure to anti-tumor necrosis factor agents and vedolizumab. Furthermore, the fecal lactoferrin trajectory was the most valuable predictor of endoscopic, clinical, and histological remission. Compared to the high/moderate-rapid decrease trajectory group, the moderate-slow decrease, high-slow decrease, and high-stable groups had adjusted odds ratios (95% confidence interval) of 0.38 (0.18, 0.78; P = 0.010), 0.47 (0.23, 0.93; P = 0.032), and 0.33 (0.17, 0.63; P = 0.001), respectively, of 1-year endoscopic remission. Patients with high/moderate-rapid decrease trajectories also had the highest likelihood of achieving clinical and histological remission. Finally, we developed a patient-stratification scheme based on fecal lactoferrin trajectories and concentrations. Patients with good, moderate, and poor prognoses in the scheme had a distinct probability of achieving 1-year endoscopic remission (52.7%, 30.9%, and 12.8%, respectively).

Conclusions: The trajectory of fecal lactoferrin is a valuable prognostic factor for 1-year remission in UC.

Background: Current knowledge on apolipoprotein A1 (APOA1) in hepatocellular carcinoma (HCC) is fragmented and even contradictory. Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism.

Methods: We collected 49 RNA-seq datasets, 40 cell line types data and 70 scRNA pan-cancer datasets public available, including 17 HCC datasets (1754 tumor samples), and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics. APOA1 impacting on the HCC tumor microenvironment (TME) was analyzed using intensive data mining. Methylation sequencing, flow cytometry, quantitative PCR, western blot, immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation.

Results: The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC, primarily involved in cholesterol efflux. Consistent findings at histology, serology, and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCC. Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC. The cell cycle, DNA replication, mismatch repair pathways, and tumor cell proliferation were less observed in the HCC APOA1^high subgroup. The favorable immunoregulatory abilities of APOA1 showed interesting findings: a positive correlation between APOA1 and anti-tumor immune cells (NK, CD8⁺ T cells) and a negative association with immune cells exerting immunosuppressive effects, including M2 macrophages.

Conclusion: This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments. Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinical target for HCC assessment and intervention in the future.

A growing number of early-stage lung cancers presenting as malignant pulmonary nodules have been diagnosed because of the increased adoption of low-dose spiral computed tomography. But pure solid T1 lung cancer with ≤3 cm in the greatest dimension is not always at an early stage, despite its small size. This type of cancer can be highly aggressive and is associated with pathological involvement, metastasis, postoperative relapse, and even death. However, it is easily misdiagnosed or delay diagnosed in clinics and thus poses a serious threat to human health. The percentage of nodal or extrathoracic metastases has been reported to be >20% in T1 lung cancer. As such, understanding and identifying the aggressive characteristics of pure solid T1 lung cancer is crucial for prevention, diagnosis, and therapeutic strategies, and beneficial to improving the prognosis. With the widespread of lung cancer screening, these highly invasive pure solid T1 lung cancer will become the main advanced lung cancer in future. However, there is limited information regarding precision medicine on how to identify these "early-stage" aggressive lung cancers. To provide clinicians with new insights into early recognition and intervention of the highly invasive pure solid T1 lung cancer, this review summarizes its clinical characteristics, imaging, pathology, gene alterations, immune microenvironment, multi-omics, and current techniques for diagnosis and prediction.

Inflammatory bowel diseases (IBDs) are complex chronic disorders of the gastrointestinal tract with the following two subtypes: Crohn's disease and ulcerative colitis. Disease presentation and progression within and across IBDs, especially Crohn's disease, are highly heterogeneous in the location, severity of inflammation, intestinal stenosis and obstruction, and extraintestinal manifestations. Clinical classifications fail to accurately predict the disease course and response to therapies. To date, most IBD genetic associations are derived from individuals of European ancestries, leading to a limitation of the discovery and application of IBD genetics in the rest of the world populations. In this mini-review, we summarize the latest progress of genome-wide association studies of IBD across global ancestries especially the Chinese population, the similarities and differences in genetic architecture between European and East Asian ancestries, as well as, the clinical significances relevant to IBD genetic study.

Owing to the advances in surgical technology, most solid tumours can be controlled by surgical excision. The priority should be tumour control, while some routine perioperative management might influence cancer progression in an unnoticed way. Moreover, it is increasingly recognized that effective perioperative management should include techniques to improve postoperative outcomes. These influences are elucidated by the different functions of circulating biomarkers in cancer patients. Here, circulating biomarkers with two types of clinical functions were reviewed: (i) circulating biomarkers for cancer progression monitoring, for instance, those related to cancer cell malignancy, tumour microenvironment formation, and early metastasis, and (ii) circulating biomarkers with relevance to postoperative outcomes, including systemic inflammation, immunosuppression, cognitive dysfunction, and pain management. This review aimed to provide new perspectives for the perioperative management of patients with cancer and highlight the potential clinical translation value of circulating biomarkers in improving outcomes.

Objectives: Alopecia areata (AA) is an autoimmune-related non-cicatricial alopecia, with complete alopecia (AT) or generalized alopecia (AU) as severe forms of AA. However, there are limitations in early identification of AA, and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA.

Methods: We obtained two AA-related datasets from the gene expression omnibus database, identified the differentially expressed genes (DEGs), and identified the module genes most related to severe AA through weighted gene co-expression network analysis. Functional enrichment analysis, construction of a protein-protein interaction network and competing endogenous RNA network, and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA. Subsequently, pivotal immune monitoring genes (IMGs) were screened through multiple machine-learning algorithms, and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic.

Results: A total of 150 severe AA-related DEGs were identified; the upregulated DEGs were mainly enriched in immune response, while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development. Four IMGs (LGR5, SHISA2, HOXC13, and S100A3) with good diagnostic efficiency were obtained. As an important gene of hair follicle stem cells stemness, we verified in vivo that LGR5 downregulation may be an important link leading to severe AA.

Conclusion: Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA, and identification of four potential IMGs, which is helpful for the early diagnosis of severe AA.