BACKGROUND: Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes. METHODS: Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated using χ2 tests. Overall survival (OS) was calculated through the Kaplan-Meier method. RESULTS: A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations including EGFR (52.14%), KRAS (12.14%), and ALK (8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutated EGFR had better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009-2013, the prognosis of stage I patients in 2014-2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports. CONCLUSIONS Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.
Humans ; Male ; Female ; Aged ; Lung Neoplasms/genetics* ; Adenocarcinoma/pathology* ; Prognosis ; Survival Rate ; Mutation ; ErbB Receptors/genetics* ; Neoplasm Staging ; Retrospective Studies

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan, report the new mutation sites of SLC26A4 gene, further clarify the mutation spectrum of SLC26A4gene, and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear, so as to provide basis for clinical and genetic diagnosis of deafness. Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology, Kunming Children's Hospital from August 2016 to September 2021. Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct. According to the genetic test results, the children who underwent temporal bone CT examination were divided into two groups: SLC26A4 biallelic mutation group（homozygous mutation and compound heterozygous mutation）, monoallelic mutation group, and the association with inner ear CT phenotype was analyzed, and the new sites were summarized and analyzed. Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation. Three new variants of SLC26A4 gene were found; CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected. Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.
Child ; Humans ; Mutation Rate ; Membrane Transport Proteins/genetics* ; China ; Hearing Loss, Sensorineural/diagnosis* ; Mutation ; Vestibular Aqueduct ; Vestibular Diseases/pathology* ; Deafness/genetics*

Covid-19 pandemic has caused hundreds of thousands deaths and millions of infections and continued spreading violently. Although researchers are racing to find or develop effective drugs or vaccines, no drugs from modern medical system have been proven effective and the high mutant rates of the virus may lead it resistant to whatever drugs or vaccines developed following modern drug development procedure. Current evidence has demonstrated impressive healing effects of several Chinese medicines (CMs) for Covid-19, which urges us to reflect on the role of CM in the era of modern medicine. Undoubtedly, CM could be promising resources for developing drug candidates for the treatment of Covid-19 in a way similar to the development of artemisinin. But the theory that builds CM, like the emphasis of driving away exogenous pathogen (virus, etc.) by restoring self-healing capacity rather than killing the pathogen directly from the inside and the 'black-box' mode of diagnosing and treating patients, is as important, yet often ignored, an treasure as CM herbs and should be incorporated into modern medicine for future advancement and innovation of medical science.
Antiviral Agents/therapeutic use* ; COVID-19/therapy* ; Disease Outbreaks ; Drug Development/standards* ; Drug Resistance, Viral/genetics* ; Drug Therapy, Combination ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Medicine, Chinese Traditional/trends* ; Mutation Rate ; Pandemics ; Phytotherapy/methods* ; SARS-CoV-2/physiology*

OBJECTIVE: To investigate the expression of CD73 in acute myeloid leukemia (AML) patients with NPM1 mutant and wild-type, and to evaluate the therapeutic efficacy and prognosis of CD73 to the AML patients. METHODS: 160 patients with AML treated in our hospital from June 2015 to June 2019 were enrolled, and 40 non-AML bone marrow samples from healthy people were selected as controls during the same period. The expression of CD73 in healthy people, NPM1 mutation and NPM1 wild-type AML patients were compared, and the relationship between the expression of CD73 and its clinicopathological characteristics, as while as efficacy in AML patients were analyzed. The patients were followed up, and the influence of CD73 to the prognosis of different AML patients was analyzed. RESULTS: The positive expression rate of CD73 in AML patients (23.75%) was significantly higher than that in the healthy control group (0.62%), and the positive expression rate of CD73 in AML patients with NPM1 mutation (74.75%) was significantly higher than that with NPM1 wild-type (25.51%) (both P<0.001). AML patients with CD73 positive expression was associated with age, FAB typing, disease risk classification, and NPM1 gene mutation (both P<0.05). The overall survival rate of AML patients with NPM1 gene mutation was 75.98%, which was significantly higher than the patients with NPM1 wild-type (34.68%)(P<0.001), the median survival time of AML patients with NPM1 gene mutation in the CD73 CONCLUSION The expression of CD73 was increased in AML patients with NPM1 gene mutation, and CD73 showed different prognostic significance in AML patients with different NPM1 gene mutation. The combination of clinicopathologic features, CD73 expression and NPM1 gene in AML patients is helpful to determine their prognosis and guide the formulation of relevant treatment plans.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Nuclear Proteins/genetics* ; Prognosis ; Survival Rate ; fms-Like Tyrosine Kinase 3

OBJECTIVE: To investigate the relationship between JAK2 gene mutation and clinical indicators in patients with myeloproliferative neoplasms (MPN). METHODS: 122 MPN patients in the Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2017 to January 2020 were retrospectively analyzed. The relationship between JAK2 gene mutation and sex, age, peripheral blood cell count, splenomegaly, and thrombosis and bleeding events were analyzed. RESULTS: In 122 patients with MPN, the patients with polycythemia vera (PV) accounted for 36 (29.5%), the patients with essential thrombocythemia (ET) accounted for 56 (45.9%), the patients with myelofibrosis (MF) accounted for 30 (24.6%). The JAK2 gene mutation rate in MPN patients was 64.6% (79/122), and the JAK2 gene mutation rate in PV, ET and MF groups were 77.7% (28/36), 60.7% (34/56) and 56.7% (17/30), the JAK2 gene mutation rate of the patients in PV group was statistically significant as compared with those in the ET group (P＜0.05). The hemoglobin (Hb) count of the patients in JAK2 gene mutation group was higher than those in wild-type group ［(150.0±39.6)g/L vs (129.4±38.9)g/L, P＜0.05］; the white blood cell (WBC) count of the patients in JAK2 gene mutation group was higher than those in the wild type group ［(9.5±4.7)×10 CONCLUSION The mutation rate of JAK2 gene in MPN patients is higher, and the mutation rate of JAK2 gene in PV patients is higher than that in ET and MF patients; JAK2 gene mutations in MPN patients are related to hemogram index; the incidence of splenomegaly is the highest in MF patients, and splenomegaly is related to the occurrence of JAK2 gene mutations in MF patients.
Humans ; Janus Kinase 2/genetics* ; Mutation Rate ; Myeloproliferative Disorders/genetics* ; Polycythemia Vera ; Retrospective Studies

OBJECTIVE: To study the instability of mitochondrial DNA（mt DNA） D-loop region genes in patients with Leukemia. METHODS: The HV-1 and HV-2 regions of D-loop region in 24 patients with leukemia were amplificated and sequenced, then their results were compared with revised Cambridge reference sequence (rCRS) and Databank mtDB. The mutation rate was detected by SPSS 22.0 statistics software. RESULTS: The total mutation rate in patients was 95.83% (23/24), the detection showed 82 mutated genes, out of which 47 (57.32%) mutated genes located in HV-1 region, 35 (42.68%) mutated genes in HV-2 region. The comparison showed that the mutation rate in untreated (UT) group and treated (T) group of AML patients was (2.37±0.82)×10 and (4.76±2.45)×10 respectively(P＜0.01), the mutation rate in PR and CR groups of treated AML patients was (5.10±2.56)×10 and (4.51±2.51)×10 respectively (P＜0.05), the comparison among M3 group showed that the mutation rates in UT, PR and CR groups were (2.55±0.63)×10, (5.37±3.41)×10 and (3.71±1.65)×10 respectively (P＞0.05). CONCLUSION The more high mutation rate and many kinds of mutation types exist in D-loop region, suggesting that the genes in D-loop region display the more strong instability, the chemotherapy may aggravate the instability of genes in D-loop region.
DNA, Mitochondrial ; Humans ; Leukemia ; Mitochondria ; Mutation ; Mutation Rate

Breast cancer is the second most common cancer in Korean women. Germline mutations in the BRCA1 and BRCA2 genes cause hereditary breast cancer and are detected in 15–20% of hereditary breast cancer. We investigated the BRCA1 and BRCA2 mutations in 114 familial breast cancer patients using next-generation sequencing. We confirmed 20 different mutations of BRCA1 and BRCA2 in 25 subjects (21.9%). Two such mutations in eight patients were novel (not reported in any variant database or previous study). Six mutations have been reported as disease-causing mutations in public databases. Seven mutations were found only in a single nucleotide polymorphism database and one mutation has been reported in Korea. The BRCA1/2 mutation frequency was similar to that of other studies on familial breast cancer patients in the Korean population. Further studies should examine more cases and mutations of whole exons.
BRCA1 Protein ; BRCA2 Protein ; Breast Neoplasms ; Breast ; Exons ; Female ; Genes, BRCA2 ; Germ-Line Mutation ; Humans ; Korea ; Mutation Rate ; Polymorphism, Single Nucleotide

PURPOSE: The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis. MATERIALS AND METHODS: Tumors from 507 breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed. RESULTS: The AKT1 mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1 mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival. CONCLUSION: A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.
Asian Continental Ancestry Group* ; Breast Neoplasms* ; Breast* ; China ; Estrogens ; Exons ; Humans ; Mutation Rate ; Phenotype ; Prevalence* ; Prognosis ; Prospective Studies ; Receptor, Epidermal Growth Factor

mutation status in breast cancers, having a mutation frequency of approximately 0.6%.CONCLUSION: KRAS mRNA expression was significantly associated with breast cancer prognosis. It was found to be an independent prognostic factor for breast cancer. Prognostic role of KRAS mRNA expression was effective only in luminal A subtype. Further studies are needed to validate the prognostic role of KRAS mRNA expression in breast cancer, thus paving a way for clinical application of KRAS in practice.]]>
Breast Neoplasms ; Breast ; Classification ; Genome ; Methylation ; Multivariate Analysis ; Mutation Rate ; Phenobarbital ; Prognosis ; ras Proteins ; RNA ; RNA, Messenger

BACKGROUND: In the present multi-institutional study, the prevalence and clinicopathologic characteristics of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were evaluated among Korean patients who underwent thyroidectomy for papillary thyroid carcinoma (PTC).METHODS: Data from 18,819 patients with PTC from eight university hospitals between January 2012 and February 2018 were retrospectively evaluated. Pathology reports of all PTCs and slides of potential NIFTP cases were reviewed. The strict criterion of no papillae was applied for the diagnosis of NIFTP. Due to assumptions regarding misclassification of NIFTP as non-PTC tumors, the lower boundary of NIFTP prevalence among PTCs was estimated. Mutational analysis for BRAF and three RAS isoforms was performed in 27 randomly selected NIFTP cases.RESULTS: The prevalence of NIFTP was 1.3% (238/18,819) of all PTCs when the same histologic criteria were applied for NIFTP regardless of the tumor size but decreased to 0.8% (152/18,819) when tumors ≥1 cm in size were included. The mean follow-up was 37.7 months and no patient with NIFTP had evidence of lymph node metastasis, distant metastasis, or disease recurrence during the follow-up period. A difference in prevalence of NIFTP before and after NIFTP introduction was not observed. BRAF(V600E) mutation was not found in NIFTP. The mutation rate for the three RAS genes was 55.6% (15/27).CONCLUSIONS: The low prevalence and indolent clinical outcome of NIFTP in Korea was confirmed using the largest number of cases to date. The introduction of NIFTP may have a small overall impact in Korean practice.
Carcinoma, Papillary ; Diagnosis ; Follow-Up Studies ; Genes, ras ; Hospitals, University ; Humans ; Korea ; Lymph Nodes ; Mutation Rate ; Neoplasm Metastasis ; Pathology ; Prevalence ; Protein Isoforms ; Recurrence ; Retrospective Studies ; Thyroid Gland ; Thyroid Neoplasms ; Thyroidectomy