[Analysis of the Efficacy and Prognosis Factors of Acute Myeloid Leukemia with a Combination Therapy of Venetoclax].

OBJECTIVE: To explore the efficacy and prognosis factors of acute myeloid leukemia with a combination therapy of venetoclax. METHODS: A retrospective analysis was performed on the clinical data of AML patients treated with a combination therapy of venetoclax from March 2020 to April 2023 in the First Hospital of Lanzhou University. The efficacy, adverse reactions and survival were observed, and the influencing factors were analyzed. RESULTS: A total of 74 AML patients were included in this study, including 43 initially treated AML and 31 relapsed or refractory AML (R/R AML). The median age of 43 initially treated AML patients was 65 years old, the composite complete remission (cCR) rate was 67.4% (29/43), the objective response rate (ORR) was 72.1% (31/43), and the median overall survival (OS) was 17.3 months. The median age of 31 R/R AML patients was 51 years old, with a cCR rate of 38.7% (12/31), an ORR of 58.1% (18/31), and a median OS of 7.1 months. Sex, the blood cell count before VEN, gene mutation and prognosis stratification were related to whether to obtain cCR. Failure to obtain cCR was an independent risk factor for adverse outcomes. CONCLUSION: A combination therapy of venetoclax is safe and efficacious for AML. Its efficacy and survival are affected by molecular biology, cytogenetics and other factors.

[The Correlation of Gene Mutation and Clinical Characteristics in Patients with Myelodysplastic Syndrome and Prognostic Analysis].

OBJECTIVE: To explore the correlation between gene mutations and clinical characteristics, prognosis of myelodysplastic syndromes (MDS). METHODS: Clinical data of 131 patients with MDS were collected from the First Hospital of Lanzhou University from June 2015 to February 2023, which 19 of them developed into secondary acute myeloid leukemia (sAML) during follow-up time. Second generation sequencing technology was used to detect the mutation types of MDS disease-related genes, drawn gene maps, and analyzed their correlation and prognosis based on the clinical data of patients. RESULTS: The median age of 131 MDS patients was 58(17-86) years old. The ratio of male to female was 1.3∶1. A total of 148 gene mutations and 25 types were found in the center. U2AF1 and ASXL1 were often co-mutations with other genes, which were accompanied by 20q- and normal karyotype (NK) respectively. SETBP1 and SRSF2 were more common in patients over 60 years old, while NPM1 and WT1 under 60 years. Older patients had a higher the number of genetic mutations than younger patients. The incidence of SF3B1 and RUNX1 in males was higher than females and DNMT3A in females was higher than males. The number of gene mutations in sAML was higher than MDS (1.8 vs 1.0, P =0.006). The univariate and multivariate analysis showed that IPSS-R prognostic score≥3.5, TP53 were adverse factors for poor prognosis in MDS patients. Patients with monoallelic mutation（ma-TP53）and wild-type（wt-TP53） TP53 had OS better than biallelic mutation（bi-TP53）(P =0.003). The OS of MDS patients was better than sAML(P =0.01) and transplant patients was significantly better than nontransplant patients(P =0.036). CONCLUSION: Gene mutation is closely related to cytogenetic indexes and clinical features (peripheral blood cell count, sex, age). IPSS-R prognostic score and TP53 were risk factors affecting OS in MDS patients.

Capsid protein from red-spotted grouper nervous necrosis virus induces incomplete autophagy by inactivating the HSP90ab1-AKT-MTOR pathway.

As a highly important fish virus, nervous necrosis virus (NNV) has caused severe economic losses to the aquaculture industry worldwide. Autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of several viruses. Although NNV can induce autophagy to facilitate infection in grouper fish spleen cells, how it initiates and mediates autophagy pathways during the initial stage of infection is still unclear. Here, we found that red-spotted grouper NNV (RGNNV) induced autophagosome formation in two fish cell lines at 1.5 and 3 h post infection, indicating that autophagy is activated upon entry of RGNNV. Moreover, autophagic detection showed that RGNNV entry induced incomplete autophagy by impairing the fusion of autophagosomes with lysosomes. Further investigation revealed that binding of the RGNNV capsid protein (CP) to the Lateolabrax japonicus heat shock protein HSP90ab1 (LjHSP90ab1), a cell surface receptor of RGNNV, contributed to RGNNV invasion-induced autophagy. Finally, we found that CP blocked the interaction of L. japonicus protein kinase B (AKT) with LjHSP90ab1 by competitively binding the NM domain of LjHSP90ab1 to inhibit the AKT-mechanistic target of the rapamycin (MTOR) pathway. This study provides novel insight into the relationship between NNV receptors and autophagy, which may help clarify the pathogenesis of NNV.

Production of functional sperm from in vitro-cultured premeiotic spermatogonia in a marine fish.

In vitro production of functional gametes can revolutionize reproduction by reducing generation intervals and accelerating genetic breeding in aquaculture, especially in fish with relatively long generations. Nevertheless, functional sperm production from in vitro-cultured spermatogonia remains a challenge in most aquaculture fish. In this study, we isolated and characterized premeiotic spermatogonia from marine four-eyed sleepers ( Bostrychus sinensis), which are prone to ovotesticular or sterile testicular development, and induced the differentiation of the spermatogonia into flagellated sperm in a three-dimensional (3D) culture system. Artificial insemination indicated that the in vitro-derived sperm were capable of fertilizing mature oocytes to develop into normal larvae. Furthermore, melatonin significantly promoted spermatogonia proliferation and differentiation through the ERK1/2 signaling pathway, and thus increased the efficiency in functional sperm production. The 3D culture system and resulting functional sperm hold great promise for improving the genetic breeding of aquaculture fish.

Identification of differentially-expressed genes in early developmental ovary of Yellow River carp (Cyprinus carpio var) using Suppression Subtractive Hybridization.

Ovary development appears to be under polygenic control, and is influenced by multiple genetic factors that may vary from organism to organism. To gain a better insight into the molecular mechanisms of carp ovary development, Suppression Subtractive Hybridization (SSH) DNA libraries in two species of Yellow River carp were analyzed. Primordial gonads and stage II ovaries were used as testers, and adult ovaries as drivers. One hundred and fifty differentially-expressed candidate genes were examined by Southern blot microarray hybridization. We identified 41 differentially-expressed genes in the PG (Primordial gonad) library and 37 in the stage II ovary library. Gene Ontology Biological Pathway analysis showed the genes were involved in signal transduction, proteolysis process, cell differentiation, TGF-ß signal and other biological responses. Twenty-two candidate genes were selected and further characterized using qRT-PCR. Pvalb, epd, and MYH were found specifically expressed in PG, while bmp2b, desmin and fp1 were specifically expressed in stage II ovary. Our results indicate that these genes could be used as biomarkers of the early development of carp ovary. This finding will provide a basis for further understanding of the complex gonad developmental molecular mechanisms in Yellow River carp.

Revision of series Gravesiana (Adiantum L.) based on morphological characteristics, spores and phylogenetic analyses.

Since the adoption of some ambiguous and quantitative characters in Flora Republicae Popularis Sinicae 3(1), species identifications of the series Gravesiana have been in disarray, requiring clarification. Two hundred and fifty-nine individuals from 47 different populations were collected for the estimation of morphological characters and phylogenetic analyses. Spores of 26 populations were observed through scanning electron microscope. Our results were different from those of previous research: (1) six identifiable species, rather than five species observed previously, were confirmed in the series Gravesiana, they are A. gravesii, A. juxtapositum, A. mariesii, A. dentatum, A. longzhouensis and A. obovatum, of which the latter three are newly recognized species. (2) Thirteen characters were measured and estimated through the program Mesquite v. 2.71. The character whether the pinna stalks were 1/3-1/2 times longer than the pinna was used to distinguish A. gravesii and A. lianxianense previously and was found to be unreliable here, whereas such characters as the height of the plant (H), pinna aligned forms (FP), number of pinna (NP), pinna margin (M), number of veins flabellate at base (NV), sori number and shape per pinna (NSS), pinna texture (T), and powder-covered or not on the abaxial surface of the pinna (P) are estimated to be stable and reliable characters useful for identification. Descriptions of new species and their retrieve keys are also listed. (3) Surface ornamentations and spore sizes are helpful for us to distinguish species in series Gravesiana.

[Study on the relationship between child abuse, parent-child separation in childhood and the aggressive behavior in adolescence among 1417 junior high school students].

OBJECTIVE: To explore the relationship between aggressive behaviors, parent-child separation and experience of childhood abuse among junior high school students. METHODS: A total of 1417 students in ordinary junior high schools from 3 townships in Huoshan, Anhui were involved in this study. Self-made questionnaire was used to estimate aggressive behaviors, parent-child separation in childhood, child abuse and social demographic information of the students under this study. RESULTS: Related scores (2.52 ± 0.78) on physical aggression in boys was higher than in girls (2.29 ± 0.79) while the scores related to anger (2.60 ± 0.82) and hostility (2.58 ± 0.80) in girls, were higher than those in boys (2.41 ± 0.75, 2.47 ± 0.78), all with statistically significant differences (P < 0.05). Scores related to different types of aggressive behaviors and the scores in total, were higher in students from the senior class (P < 0.001). Scores on items as verbal aggression, hostility and in total, were higher in those adolescents which had undergone maternal-child separation during their childhood (P < 0.05). Scores on hostility and in total, were higher in those adolescents which had suffered from father-child separation during their childhood (P < 0.05). Scores related to anger, hostility and in total, were higher in those adolescents which had undergone both parent-child separation when they were much younger (P < 0.05). Students who had suffered from various types of repeated abuse showed higher scores in various types of aggressive behaviors and in total, than those who did not have the same experience. Most of the differences among groups were statistically significant (P < 0.05). CONCLUSION: Students that suffered parent-child separation in their earlier childhood and with repeated experiences of abuse in childhood appeared to be risk factors causing aggressive behaviors to develop during the age of adolescence.