Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms.

Despite the identification of driver mutations leading to the initiation of myeloproliferative neoplasms (MPNs), the molecular pathogenesis of MPNs remains incompletely understood. Here, we demonstrate that growth arrest and DNA damage inducible gamma (GADD45g) is expressed at significantly lower levels in patients with MPNs, and JAK2V617F mutation and histone deacetylation contribute to its reduced expression. Downregulation of GADD45g plays a tumor-promoting role in human MPN cells. Gadd45g insufficiency in the murine hematopoietic system alone leads to significantly enhanced growth and self-renewal capacity of myeloid-biased hematopoietic stem cells, and the development of phenotypes resembling MPNs. Mechanistically, the pathogenic role of GADD45g insufficiency is mediated through a cascade of activations of RAC2, PAK1 and PI3K-AKT signaling pathways. These data characterize GADD45g deficiency as a novel pathogenic factor in MPNs.

[Advances of structure and mechanisms of bromodomain-containing protein 4 and its related research in tumors].

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.

Monocyte count is associated with the severity of human adenovirus pneumonia in hospitalized children aged less than 6 years.

BACKGROUND: Human Adenovirus (HAdV) pneumonia is common in young children and infants. Overall, 7-8% of all viral respiratory illnesses among children for less than 5 years are induced by HAdVs. Unfortunately little is known about the role of monocyte count in the disease severity. METHODS: Data were gathered from 595 children (age < 6 years) who were diagnosed with HAdV infection at the 1st People's Hospital (Changde City, China) between January 2019 and December 2019. There were 181 cases of severe adenovirus pneumonia. RESULTS: The correlation between the patients' monocyte count and the severity of HAdV pneumonia was estimated by performing a multiple linear regression analysis. The results showed a negative association (OR: 0.53, 95% CI 0.31 to 0.89, P < 0.05). We further built Generalized Additive Models (GAMs) and demonstrated that the monocyte count had a non-linear association with severe HAdV pneumonia. The inflection point of monocyte count detected in the two-stage linear regression model was 1.5. On the left side of this point, the monocyte count was negatively interrelated (OR: 0.26, 95% CI 0.13 to 0.52, P < 0.001), while on the opposite side, there was a positive association (OR: 7.48, 95% CI 1.30 to 43.08, P < 0.05). CONCLUSIONS: Based on the results of this investigation, we established a link between monocyte count and the severity of HAdV pneumonia. Monocyte count is negatively associated with severe HAdV pneumonia. The inflection point of monocyte count detected in the two-stage linear regression model was 1.5 × 109/L.

[Value of CD, MPO, Ki-67 and C-MYC Positive Rate in the Pathological Tissues and C-MYC Gene of Patients with T-LBL/ALL for Predicting Prognosis].

OBJECTIVE: To explore the value of of CD, MPO, Ki-67, C-MYC positive rates in the pathological tissues and C-MYC gene of patients with T-LBL/ALL for predicting Prognosis. METHODS: Ninty cases of T-LBL/ALL patients in our hospital were selected and included in the T-LBL/ALL group, and 30 cases of lymphnode reactive hyperplasia were selected as control group. Immunohistochemical staining was used to detect the changes of CD, MPO, Ki-67 and C-MYC positive rate in 2 groups, and the changes of C-MYC gene were detected by fluorescence in situ hybridization. RESULTS: In 90 patients with T-LBL/ALL, there were CD1a+ 34 cases (37.8%), CD3+ 67 cases (74.4%), epsilon CD3+ 47 cases (52.2%), CD7+ 85 cases (94.4%), CD10+ 33 cases (36.7%), CD34+ 22 cases (24.4%), CD43+ 48 cases (53.3%), CD45RO+ 46 cases (51.1%), CD99+ 88 cases (97.8%), TDT+ 85 cases (94.4%); and CD23, CD20, and MPO all were negative; Ki-67>80% 47 cases (52.2% cases), Ki-67≤80%, 43 cases (47.8%). In 90 T-LBL/ALL patients, the positive rate of C-MYC (66.7%) was significantly higher than the control group (positive rate 0.0%) (P< 0.05); the Ki-67 index, mediastinal widening of T-LBL/ALL patients and the positive rate of C-MYC positively were correlated (P< 0.05). The overall survival rate (44.0%) of C-MYC negative patients was significantly higher than that of C-MYC positive patients (0.0%). The overall survival rate of C-MYC negative patients was significantly higher than that of C-MYC positive patients (P< 0.05).Ann Arbor staging, LDH, bone marrow involvement, mediastinal widening, Ki-67 positive index, and C-MYC protein expression of patients with T-LBL/ALL did not correlated with increased C-MYC gene breakage and copy number (P> 0.05). CONCLUSION: The overall survival rate of C-MYC positive patients decreases, which positively correlates with Ki-67 positive index and mediastinal width, suggesting that the prognosis of the patients with C-MYC protein expression is poorer.

[Clinical characteristics in adults and children with vasovagal syncope].

OBJECTIVE: To analyze the clinical characteristics in adults and children with vasovagal syncope (VVS). METHODS: Clinical data including head-up tilt table (HUTT) results were analyzed and compared in 136 children (mean age 12.3 +/- 2.7 years, 50 boys, 86 girls) and 119 adults (mean age 36.4 +/- 14.0 years, 29 men, 90 women) with VVS. RESULTS: (1) There were more female VVS patients in adults group than that in children group (male and female ratio: children group 1:1.7 and adults group 1:3.1, P = 0.033) in this cohort. (2) The incidence of chest distress in adults group was significantly higher than that in children group [45.4 (54/119) vs. 27.2% (37/136), P = 0.003] while the incidence of headache [10.9% (13/119) vs. 20.6% (28/136), P = 0.036] and abdominal pain in children group was significantly higher than that in adults group [7.6% (9/119) vs. 19.1% (26/136), P = 0.008]. (3) Incidences of muggy environment [22.8% (26/114) vs. 12.5% (17/136), P = 0.032] and urination VVS [9.7% (11/114) vs. 1.5% (2/136), P = 0.004] were significantly higher in adults group than those in children group. (4) The mean time of mixed response vasogal episode in adults group was significantly longer than that in children group in sublingual nitroglycerin head-up tilt table test (SNHUT) stage (5.04 +/- 2.27 min vs. 3.50 +/- 1.24 min, P = 0.036). CONCLUSIONS: The incidences of chest distress, muggy environment and urination VVS were more often and the mean time of vasogal episode of mixed response in SNHUT stage was longer in adults VVS while the incidence of abdominal pain and headache was higher in children VVS patients compared to adults VVS patients.