Protein structuromics: A new method for protein structure-function crosstalk in glioma.

Glioma is a type of tumor that starts in the glial cells of the brain or spine. Since the 1800s, when the disease was first named, its survival rates have always been unsatisfactory. Despite great advances in molecular biology and traditional treatment methods, many questions regarding cancer occurrence and the underlying mechanism remain to be answered. In this study, we assessed the protein structural features of 20 oncogenes and 20 anti-oncogenes via protein structure and dynamic analysis methods and 3D structural and systematic analyses of the structure-function relationships of proteins. All of these results directly indicate that unfavorable group proteins show more complex structures than favorable group proteins. As the tumor cell microenvironment changes, the balance of oncogene-related and anti-oncogene-related proteins is disrupted, and most of the structures of the two groups of proteins will be disrupted. However, more unfavorable group proteins will maintain and refold to achieve their correct shape faster and perform their functions more quickly than favorable group proteins, and the former thus support cancer development. We hope that these analyses will help promote mechanistic research and the development of new treatments for glioma.

A real-world study on diagnosis and prognosis of light-chain cardiac amyloidosis in Southern China.

BACKGROUND: Light-chain cardiac amyloidosis (AL-CA) has been highly valued in developed countries, but in developing countries, the recognition and diagnosis of this condition is still limited. There are currently few reports on a large number of Chinese patients with AL-CA. The present study aimed to report real-world clinical characteristics and prognosis of AL-CA in China. METHODS AND RESULTS: Consecutive patients with AL-CA diagnosed at the Second Xiangya Hospital of Central South University between June 2012 and September 2020 were reviewed. A total of 170 patients with AL-CA have been recruited, whose mean ages were 60.81 ± 10.46. 70.59% of the patients were male. They were from eight provinces in southern China, 55.7% were referred patients, and 37.3% had been misdiagnosed previously. 64 (37.6%) patients received chemotherapy. The median survival time for patients with AL-CA was 8.00 months, and survival time for patients who received chemotherapy was 13.00 months, which was significantly longer than that of patients with palliative treatment (13.00 vs 6.00, p = 0.004). CONCLUSIONS: Although clinicians have improved their understanding of AL-CA in recent years, the prognosis of AL-CA is still poor, and the misdiagnosis rate and missed diagnosis rate are still very high in China. It is imperative to improve the recognition and early diagnosis of this condition, which may require multidisciplinary collaboration among cardiologists, hematologists and nephrologists.

Identification of a nonsense mutation in TNNI3K associated with cardiac conduction disease.

BACKGROUND: Cardiac conduction disease (CCD) is a common cardiovascular disease which can lead to life-threatening conditions. The importance of heredity in CCD has been realized in recent years. Several causal genes have been found to be implicated in CCD such as SCN5A, TRPM4, SCN1B, TNNI3K, LMNA, and NKX2.5. To date, only four genetic mutations in TNNI3K have been identified related to CCD. METHODS: Whole-exome sequencing (WES) was carried out in order to identify the underlying disease-causing mutation in a Chinese family with CCD. The potential mutations were confirmed by Sanger sequencing. Real-time qPCR was used to detect the level of TNNI3K mRNA expression. RESULTS: A nonsense mutation in TNNI3K (NM_015978.2: g.170891C > T, c.1441C > T) was identified in this family and validated by Sanger sequencing. Real-time qPCR confirmed that the level of TNNI3K mRNA expression was decreased compared with the controls. CONCLUSIONS: This study found the first nonsense TNNI3K mutation associated with CCD in a Chinese family. TNNI3K harboring the mutation (c.1441C > T) implicated a loss-of-function pathogenic mechanism with an autosomal dominant inheritance pattern. This research enriches the phenotypic spectrum of TNNI3K mutations, casting a new light upon the genotype-phenotype correlations between TNNI3K mutations and CCD and indicating the importance of TNNI3K screening in CCD patients.

High Serum Carbohydrate Antigen (CA) 125 Level Is Associated With Poor Prognosis in Patients With Light-Chain Cardiac Amyloidosis.

Background and Aims: Patients with light-chain cardiac amyloidosis (AL-CA) are characterized by high levels of serum carbohydrate antigen 125 (CA 125). However, studies have not explored the correlation between CA 125 and AL-CA. The aim of this study was to explore the clinical implications of an increase in CA 125 in patients with AL-CA. Methods and Results: A total of 95 patients diagnosed with AL-CA at the Second Xiangya Hospital were enrolled in this study. Out of the 95 patients with AL-CA, 57 (60%) patients had elevated serum CA 125 levels. The mean age was 59.7 ± 10.0 years with 44 (77.2%) men in the high serum CA 125 group, and 61.8 ± 9.6 years with 28 (73.7%) men in the normal group. Patients with high CA 125 showed higher rates of polyserositis (79.3% vs. 60.5%, p = 0.03), higher levels of hemoglobin (117.4 ± 21.9 g/L vs. 106.08 ± 25.1 g/L, p = 0.03), serum potassium (4.11 ± 0.47 mmol/L vs. 3.97 ± 0.40 mmol/L, p = 0.049), low-density lipoprotein-cholesterol (3.0 ± 1.6 mmol/L vs. 2.3 ± 1.10 mmol/L, p = 0.01), and cardiac troponin T (96.0 pg/mL vs. 91.9 pg/mL, p = 0.005). The median overall survival times for patients with high or normal serum CA 125 were 5 and 25 months, respectively (p = 0.045). Multivariate Cox hazard analysis showed that treatment without chemotherapy (HR 1.694, 95% CI 1.121-2.562, p = 0.012) and CA 125 (HR 1.002, 95% CI 1.000-1.004, p = 0.020) was correlated with high all-cause mortality. The time-dependent receiver operating characteristic (t-ROC) curve showed that the prediction accuracy of CA 125 was not inferior to that of cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and lactate dehydrogenase (LDH) based on the area under the curve. Conclusions: CA 125 is a novel prognostic predictor. High serum CA 125 values are correlated with low overall survival, and the accuracy of predicting prognosis is similar to that of traditional biomarkers in AL-CA.