OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

OBJECTIVES: To study the clinical characteristics and prognosis of T-lineage acute lymphoblastic leukemia (T-ALL) and related prognostic factors. METHODS: A retrospective analysis was conducted on the children with T-ALL who were treated with the Chinese Children's Cancer Group Acute Lymphoblastic Leukemia (CCCG-ALL) regimen in Guangzhou Women and Children's Medical Center between April 2015 and December 2022. RESULTS: A total of 80 children were included, with a median age of 7 years and 3 months and a male/female ratio of 6:1. Among these children, the children with mediastinal mass accounted for 20% (16/80), those with central nervous system leukemia accounted for 4% (3/80), and those with testicular leukemia accounted for 1% (1/69). SIL/TAL1 was the most common fusion gene (22%, 18/80), and NOTCH1 was the most common mutation gene (69%, 37/54). The median follow-up time was 52 months, with a 5-year overall survival (OS) rate of 87.3%±4.0% and a 5-year event-free survival rate of 84.0%±4.3%. The non-central nervous system-1 group had a significantly lower 5-year OS rate than the central nervous system-1 group (66.7%±16.1% vs 90.3%±3.8%; P<0.05), and the group with minimal residual disease (MRD) ≥0.01% on day 46 of induction therapy had a significantly lower 5-year OS rate than the group with MRD <0.01% (68.6%±13.5% vs 94.8%±3.0%; P<0.05). CONCLUSIONS Children treated with the CCCG-ALL regimen tend to have a good treatment outcome. Non-central nervous system-1 status and MRD ≥0.01% on day 46 of induction therapy are associated with the poor prognosis in these children.
Humans ; Male ; Female ; Child ; Prognosis ; Child, Preschool ; Retrospective Studies ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Infant ; Adolescent ; Receptor, Notch1/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Survival Rate

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*

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 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 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

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*

Globozoospermia has been reported to be a rare but severe causation of male infertility, which results from the failure of acrosome biogenesis and sperm head shaping. Variants of dpy-19-like 2 (DPY19L2) are highly related to globozoospermia, but related investigations have been mainly performed in patients from Western countries. Here, we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations, as revealed by whole-exome sequencing. Patient 3 (P3) contained a heterozygous variant (c.2126+5G>A), P6 contained a homozygous nonsense mutation (c.1720C>T, p.Arg574^*), P8 contained compound heterozygous variants (c.1182-1184delATC, p.Leu394_Ser395delinsPhe; c.368A>T, p.His123Arg), and P9 contained a heterozygous variant (c.1182-1184delATCTT, frameshift). We also reported intracytoplasmic sperm injection (ICSI) outcomes in the related patients, finding that ICSI followed by assisted oocyte activation (AOA) with calcium ionophore achieved high rates of live births. In summary, the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.
Acrosome ; Adult ; China ; Codon, Nonsense ; Female ; Humans ; Male ; Membrane Proteins/genetics* ; Point Mutation ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Sequence Deletion ; Sperm Head ; Sperm Injections, Intracytoplasmic ; Teratozoospermia/genetics* ; Exome Sequencing

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

BACKGROUND: Most triple-negative breast cancers (TNBCs) have a high histologic grade, are associated with high endoplasmic stress, and possess a high frequency of TP53 mutations. TP53 missense mutations lead to the production of mutant p53 protein and usually show high levels of p53 protein expression. Tumor-infiltrating lymphocytes (TILs) accumulate as part of the anti-tumor immune response and have a strong prognostic and predictive significance in TNBC. We aimed to elucidate the association between p53 expression and the amount of TILs in TNBC. METHODS: In 678 TNBC patients, we evaluated TIL levels and expression of endoplasmic stress molecules. Immunohistochemical examination of p53 protein expression was categorized into three groups: no, low, and high expression. RESULTS: No, low, and high p53 expression was identified in 44.1% (n = 299), 20.1% (n = 136), and 35.8% (n = 243) of patients, respectively. Patients with high p53 expression showed high histologic grade (p < .001), high TIL levels (p = .009), and high expression of endoplasmic reticulum stress-associated molecules (p-eIF2a, p = .013; XBP1, p = .007), compared to patients with low p53 expression. There was no significant difference in disease-free (p = .406) or overall survival rates (p = .444) among the three p53 expression groups. CONCLUSIONS: High p53 expression is associated with increased expression of endoplasmic reticulum stress molecules and TIL influx.
Breast Neoplasms ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Humans ; Lymphocytes, Tumor-Infiltrating ; Mutation, Missense ; Survival Rate ; Triple Negative Breast Neoplasms