Emerging trends in the coexistence of primary lung Cancer and hematologic malignancy: a comprehensive analysis of clinicopathological features and genetic abnormalities.

BACKGROUND: The incidence of multiple primary cancers (MPC), especially involving primary lung cancer (PLC) and primary hematologic malignancies (PHM), is rising. This study aims to analyze clinicopathological features, gene abnormalities, and prognostic outcomes in individuals diagnosed with PLC-PHM MPC. METHODS: A retrospective analysis included 89 patients diagnosed with PLC-PHM MPC at the Respiratory or Hematology Departments of Ruijin Hospital from 2003 to 2022 (a total of 842,047 people). Next-generation sequencing (NGS) assessed lung cancer specimens, while Polymerase Chain Reaction (PCR) and NGS were used for hematologic malignancy specimens. Statistical analysis involved survival analysis and Cox regression. RESULTS: PLC-PHM MPC incidence surged from 1.67 per year (2011-2013) to 16.3 per year (2020-2022). The primary demographic for PLC-PHM MPC consists predominantly of elderly (average age 66 years) males (59.6%), with a high prevalence of metachronous MPC (89.9%). The prevailing histological types were lung adenocarcinoma (70.8%) in lung cancer (LC) and mature B-cell lymphomas (50.6%) in hematologic malignancies (HM). Notably, in a molecular testing cohort of 38 LC patients, 84.2% of lung cancer cases exhibited driver mutations, in which EGFR mutations frequence prevalent was 74.2%. In total group of 85 cases achieved a median overall survival (mOS) of 46.2 months, with a 5-year survival rate of 37.9% and advanced LC patients with LC gene mutations achieved a mOS was 52.6 months, with a 5-year OS rate of 30.6%. The median progression-free survival (PFS) following first-line treatment of 11 advanced patients with lung cancer-associated driver gene mutations is 26.6 months. Multivariate Cox regression revealed a favorable OS associated with surgery for LC, favorable PS score, adenocarcinoma pathology of LC, and the presence of genetic abnormalities associated with HM. CONCLUSION: PLC-PHM MPC incidence is rising, characterized by a significant proportion of lung adenocarcinoma and a high prevalence of positive driver genes, especially in EGFR. Despite suffering from two primary tumors, the PLC-PHM MPC patients had superior data of both PFS and OS, suggesting an inherently intricate background of genetic abnormalities between the two kinds of tumors.

Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report.

The present study reports a patient case with a 17α-hydroxylase deficiency accompanied by triple X syndrome. A 17α-hydroxylase deficiency leads to a very low 17α-hydroxylated steroid synthesis as well as a non-feedback increase in the adrenocorticotropic hormone level. Meanwhile, the progesterone level increases the 17α-hydroxyprogesterone level and decreases the dehydroepiandrosterone sulfate level. The patient is characterized by intractable hypokalemia, high urinary potassium, hyperaldosteronemia, hyporeninemia, hypocortisolemia, hypertension, gonadal and secondary sexual dysplasia, a decreased estrogen level, primary amenorrhea, and infertility. The imaging findings indicate a presence of multiple bilateral adrenal gland adenomas, and the sequencing indicates a missense CYP17A1-E7 gene pathogenic variant. The karyotype is a 47, XXX [3]/46, XX [47] low-level chimeric karyotype. The patient's parents are cousins. To our knowledge, this patient is the first case diagnosed with congenital adrenal hyperplasia caused by hydroxylase deficiency and triple X syndrome. The uniqueness of this case is that this patient has two very rare genetic diseases, probably due to the marriage of close relatives.

The receptor hypothesis and the pathogenesis of depression: Genetic bases and biological correlates.

Depression has become one of the most prevalent neuropsychiatric disorders characterized by anhedonia, anxiety, pessimism, or even suicidal thoughts. Receptor theory has been pointed out to explain the pathogenesis of depression, while it is still subject to debate. Additionally, gene abnormality accounts for nearly 40-50% of depression risk, which is a significant factor contributing to the onset of depression. Accordingly, studying on receptors and their gene abnormality are critical parts of the research on internal causes of depression. This review summarizes the pathogenesis of depression from six of the most related receptors and their associated genes, including N-methyl-D-aspartate receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, glucocorticoid receptor, 5-hydroxytryptamine receptor, GABAA receptor α2, and dopamine receptor; and several "non-classic" receptors, such as metabotropic glutamate receptor, opioid receptor, and insulin receptor. These receptors have received considerable critical attention and are highly implicated in the onset of depression. We begin by providing the biological mechanisms of action of these receptors on the pathogenesis of depression. Then we review the historical and social context about these receptors. Finally, we discuss the limitations of the current state of knowledge and outline insights on future research directions, aiming to provide more novel targets and theoretical basis for the early prevention, accurate diagnosis and prompt treatment of depression.

Advance in relationship between receptor gene abnormality and depression / 药学学报

Depression, a chronic syndrome with low mood, pessimism, cognitive and sleep disorders, is characterized by high incidence, high suicide rate, low consultation and treatment rate. 40%-50% of the risk of depression comes from genes, so studying on gene abnormalities serves as an important part of the research in the internal causes of depression, among which the receptor gene abnormalities are crucial factors. The study of potential receptor gene loci is expected to be new target for the treatment of depression in the future, which can provide theoretical basis for the early diagnosis, prevention and treatment of depression.