Multiscale Element-Doped Nanowire Array-Coupled Machine Learning Reveals Metabolic Fingerprints of Nonreversible Liver Diseases.

Timely detection of nonreversible liver diseases contributes greatly to reasonable therapy and quality of life. Given the current situation, minimally invasive high-specificity molecular diagnosis based on body fluid can be a good choice. Herein, a mesoporous superstructure is designed using silicon atom-doped nanowire arrays to uniformly load Pt nanoparticles on the surface to produce a desirable ionization effect. We apply the multiscale element-doped nanowire arrays to efficiently assist extraction of high-quality metabolic fingerprints from only 35 nL of serum within seconds. Using different machine learning algorithms, we establish specific biomarker panels to distinguish different liver diseases from the healthy control, with more than 90% accuracy, sensitivity, and specificity. Moreover, from established biomarker panels, we further determine key metabolites of significant difference (p < 0.01) via group comparison to realize the discrimination of different liver diseases with 100% sensitivity. Our work confirms the design protocol of an advanced diagnosis tool and lays a robust foundation for metabolic molecular diagnosis in large-scale clinical application.

[Research advances in transplantation for thalassemia major].

Thalassemia is an inherited blood disorder caused by disordered globin chain synthesis due to mutations in the regulatory genes for hemoglobin. At present, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recognized as the only curative method for treatment. Through the revolution of pretransplantation regimens and selection of donor and source of stem cells, patients' survival has been greatly improved. This article reviews the development of transplantation for thalassemia and related research advances, in order to provide suitable treatment options for clinical application.

Exosome Metabolic Patterns on Aptamer-Coupled Polymorphic Carbon for Precise Detection of Early Gastric Cancer.

Gastric cancer (GC) presents high mortality worldwide because of delayed diagnosis. Currently, exosome-based liquid biopsy has been applied in diagnosis and monitoring of diseases including cancers, whereas disease detection based on exosomes at the metabolic level is rarely reported. Herein, the specific aptamer-coupled Au-decorated polymorphic carbon (CoMPC@Au-Apt) is constructed for the capture of urinary exosomes from early GC patients and healthy controls (HCs) and the subsequent exosome metabolic pattern profiling without extra elution process. Combining with machine learning algorithm on all exosome metabolic patterns, the early GC patients are excellently discriminated from HCs, with an accuracy of 100% for both the discovery set and blind test. Ulteriorly, three key metabolic features with clear identities are determined as a biomarker panel, obtaining a more than 90% diagnostic accuracy for early GC in the discovery set and validation set. Moreover, the change law of the key metabolic features along with GC development is revealed through making a comparison among HCs and GC at early stage and advanced stage, manifesting their monitoring ability toward GC. This work illustrates the high specificity of exosomes and the great prospective of exosome metabolic analysis in disease diagnosis and monitoring, which will promote exosome-driven precision medicine toward practical clinical application.

Precise Detection of Cataracts with Specific High-Risk Factors by Layered Binary Co-Ionizers Assisted Aqueous Humor Metabolic Analysis.

Diabetes and high myopia as well-known high-risk factors can aggravate cataracts, yet clinical coping strategy remains a bottleneck. Metabolic analysis tends to be powerful for precisely detection and mechanism exploration since most of diseases including cataracts are accompanied by metabolic disorder. Herein, a layered binary co-ionizers assisted aqueous humor metabolic analysis tool is proposed for potentially etiological typing and detection of cataracts, including age-related cataracts (ARC), cataracts with diabetes mellitus (CDM), and cataracts with high myopia (CHM). Startlingly, taking advantage of the optimal machine learning algorithm and all metabolic fingerprints, 100% of accuracy, precision, and recall rates are achieved for arbitrary comparison between groups. Moreover, 11, 9, and 7 key metabolites with explicit identities are confirmed as markers of discriminating CDM from ARC, CHM from ARC, and CDM from CHM, and the corresponding area under the curve values of validation cohorts are 0.985, 1.000, and 1.000. Finally, the critical impact of diabetes/high myopia on cataracts is revealed by excavating the change levels and metabolic pathways of key metabolites. This work updates the insights of prevention and treatment about cataracts at metabolic level and throws out huge surprises and progresses metabolic diagnosis toward a reality.

Hematopoietic stem cell transplantation for thalassemia major using HLA fully-matched and mismatched donor grafts.

BACKGROUND: Until now, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only effective method to cure Thalassemia major. However, it has not been determined whether similar results can be obtained with the same conditioning regimen for both fully-matched and mismatched donors grafts. We hypothesized that using modified NF-08-TM conditioning regimen could achieve similar results for both fully and mismatched donors grafts. METHODS: This retrospective cohort study included patients with ß-thalassemia major who underwent HSCT with modified NF-08-TM conditioning regimen at Guangzhou Women and Children's Medical Centre between January 2013 and January 2019. RESULTS: Among the 257 patients (172 males) included in this study, 3 had two transplantations. Totally 193 and 67 had fully-matched and mismatched donors were examined, respectively. The median follow-up was 29 months; 6-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR) and transplantation-related mortality (TRM) were 92.08%, 90.89%, 1.24% and 8.01%, respectively. Multivariate analysis showed that human leukocyte antigen (HLA) compatibility between patient and donor was not independently associated with OS, TFS, GR or TRM. Mismatched donor graft transplantation for ß-thalassemia major is associated with similar survival outcomes and incidences of complications (except for acute GVHD) to fully-matched donor graft transplantation based on modified NF-08-TM conditioning regimen. CONCLUSIONS: In conclusion, based on the modified NF-08-TM regimen, certain mismatched donor transplantations for thalassemia major patients could achieve similar results as fully-matched donor transplantations.

Dual fluorescence in situ hybridization in detection of HER-2 oncogene amplification in primary hepatocellular carcinoma.

BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to investigate the frequency of HER-2 oncogene amplification in primary HCC and its relations to clinicopathological parameters and prognosis. METHODS: Forty-two surgical samples from patients with primary HCC were detected for their HER-2 oncogene amplification. The number of chromosome 17 and their ratio were tested by dual fluorescence in situ hybridization (FISH) technique, and then the correlations between HER-2 amplification, clinicopathological characteristics and prognosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was detected in 9 (21.4%) of the 42 primary HCCs, including 4 patients with high copy (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was associated significantly with tumor size and postoperative survival time of HCC patients (P<0.05), and the presence of HER-2 gene amplification was correlated with postoperative relapse (P=0.257), but not related to sex, age, AFP level, HBV infection, histopathological grading and clinical staging of HCC patients (P>0.05). The HER-2 oncogene copy was examined in 31 (73.8%) of the 42 primary HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 patients with aneuploidy (52.4%). No significant relations were observed between the HER-2 oncogene copy, patient sex, tumor size, histopathological grading, clinical staging, postoperative relapse and survival time (P>0.05); but the HER-2 oncogene copy was correlated significantly to age, AFP level and HBV infection (P<0.05). CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a higher frequency of chromosome 17 aneuploidy in primary HCC. HER-2 oncogene amplification may be involved in the development and progression of large HCC in some patients, and seems to be a valuably independent prognostic factor predicting the recurrence and poor survival in patients with large HCC.