Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Objective:To study the influence of different feeding patterns on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with high viral loads who received antiviral medication during pregnancy to the day of delivery.Methods:This prospective cohort study was conducted in Beijing You'an Hospital. From January 1, 2019, to March 31, 2020, and 574 pregnant women with positive hepatitis B surface antigen (HBsAg) and HBV DNA>2×10 5 IU/ml were enrolled. All participants received tenofovir, telbivudine, lamivudine, or propofol tenofovir from 24-28 weeks of gestation and discontinued on the day of delivery, and their neonates were postnatally given routine passive-active immunoprophylaxis. Based on the feeding patterns, the subjects were divided into three groups: breastfeeding ( n=257), bottle-feeding ( n=241) and mixed feeding groups ( n=76). The follow-up data were obtained from liver functions and HBV DNA level of the mothers at 6-8 weeks postpartum and HBV serological markers of infants at 7-12 months. One-way ANOVA, Student-Newman-Keuls, Chi-square test or Fisher exact test, and repeated measures ANOVA were used to analyze the data. Results:The average maternal HBV DNA levels before antiviral treatment did not differ significantly between the three groups [(7.90±0.67), (7.82±0.70), (7.83±0.70) log 10 IU/ml, F=0.912, P>0.05]. HBV DNA level before delivery in the mixed feeding group was slightly lower than that in the breastfeeding and bottle-feeding group [(3.87 ±1.08) vs (4.21±1.17) and (4.30±1.28) log 10 IU/ml, q= 3.052 and 3.831, both P<0.05], while the comparison between the latter two groups showed no significant differences ( P>0.05). After delivery, HBV DNA level in the bottle-feeding group was slightly lower than that in the breastfeeding group [(7.42±0.93) vs (7.69±0.90) log 10 IU/ml, q=4.583, P<0.05]. Among 580 infants (including six pairs of twins), only one bottle-fed infant (0.4%, 1/243) was infected with HBV through MTCT, and none in the breastfeeding or mixed feeding group ( P=0.553). Conclusions:For pregnant women with high viral loads of HBV who have received antiviral medication during pregnancy, although HBV DNA level will rebound after discontinuation upon delivery, breastfeeding is recommended considering it does not increase the risk of MTCT.

Objective:To investigate the effect of genetic polymorphisms of TPMT*2 rs1800462, TPMT*3B rs1800460, TPMT*3C rs1142345, and NUDT15 rs116855232 on the tolerance of 6-mercaptopurine (6-MP) therapy in adult acute lymphoblastic leukemia (ALL) .Methods:A total of 216 adult patients who were diagnosed with ALL and treated with cyclophosphamide, cytarabine, and 6-MP [complementary and alternative medicine (CAM) regimen] from September 2015 to December 2019 were included. Polymorphisms were detected by TaqMan SNP Genotyping Assay. Combined with clinical data, the influence of genetic polymorphism on the tolerance of 6-MP in the treatment of ALL was analyzed.Results:Among the 216 patients, 185 (85.65%) patients had B-ALL and 31 (14.35%) patients had T-ALL. 216 (100%) patients had CC genotype for both TPMT*2 rs1800462 and TPMT*3B rs1800460. The number of TT and TC genotypes for TPMT*3C rs1142345 was 209 (96.76%) and 7 (3.24%) , respectively. The allele frequency was 1.62% for TPMT*3C rs1142345. The number of CC, CT, and TT genotypes for NUDT15 rs116855232 was 166 (76.85%) , 48 (22.22%) , and 2 (0.93%) , respectively. The allele frequency was 12.04% for NUDT15 rs116855232. The TPMT*3C rs1142345 mutant group (TC+CC genotype) had less transfusion volume of packed red blood cell than the wild group (CC genotype) ( P=0.036) , and the mutant group (TC+CC genotype) had a higher risk to develop hepatotoxicity (increased aspartate aminotransferase) than the wild group (CC genotype) ( OR=9.559, 95% CI 1.135-80.475, P=0.038) . The durations of white blood cells (WBC) <1×10 9/L and absolute neutrophil count (ANC) <0.5×10 9/L in the NUDT15 rs116855232 mutation group (CT+TT genotype) were longer than that in the wild group (CC genotype) ( P=0.005, P=0.007) , and the transfusion volume of apheresis-derived platelets in the mutant group (CT+TT type) was greater than that in the wild group (CC genotype) ( P=0.014) . Conclusion:Genetic polymorphism of TMPT and NUDT15 has an effect on the tolerance of 6-MP in the treatment of adult ALL. Detecting genotypes of patients with ALL before treatment helps to optimize the dosage of 6-MP, which may help shorten the bone marrow suppression duration and reduce blood transfusion volume.

Objective:To analyze the psychological anxiety and social support of HBV-carrying pregnant women and healthy pregnant women, and provide a reference for improving nursing interventions for hepatitis B virus (HBV) -carrying pregnant women.Methods:In this cross-sectional study, totally 314 pregnant women with HBV who attended outpatient services, established health files and had clear test results in a Beijing infectious disease specialist hospital from March to April 2019, and in two other ClassⅢ Grade A hospitals in the same period 420 healthy pregnant women were selected by convenient sampling. The Sociodemographic questionnaire, Self-Anxiety Scale (SAS) and Social Support Rating Scale (SSRS) were used to investigate the pregnant women.Results:There were statistically significant differences between HBV-carrying pregnant women and healthy pregnant women in education level, household registration status, family monthly income per capita, type of medical insurance, duration of pregnancy, status of pregnancy and subjective support scores ( P<0.05) . Multiple linear regression analysis controlling related factors found that whether the pregnant women carried the HBV had no effect on their psychological anxiety ( P>0.05) , and support utilization score, age, pregnancy days and education level affected the psychological anxiety of pregnant women ( P<0.05) .There was no statistically significant difference in SAS scores between the two groups of pregnant women ( t=-0.965, P>0.05) . Conclusions:The status of HBV carrying will not affect pregnant women's psychological anxiety, and factors such as social support utilization, education level, pregnancy days and age will have effect on pregnant women's psychological anxiety. It is recommended to take corresponding intervention measures to improve the utilization of social support, thereby alleviating the psychological anxiety of pregnant women.

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients’ overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph⁺ B-ALL and Ph^- B-ALL patients. Ph^- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph⁺ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

Objective: To investigate the feasibility of multiplex real-time RT-PCR with fluorescent probes in early screening of Ph-like acute lymphoblastic leukemia (ALL) and analyze the clinical feature and prognos. Method: A total of 118 adult B-ALL patients diagnosed between October 2010 and March 2016 were enrolled in this study. Multiplex RT-PCR was used to detect the Ph-like ALL related fusion gene and CRLF2 expression in 58 BCR-ABL and MLL rearrangement negative patients. The clinical features, treatment response and prognosis were analyzed in Ph-like fusion gene positive and/or CRLF2 over-expression patients. Result: Among 58 patients, 9 patients (9/58, 15.5%) showed Ph-like ALL related fusion genes positive and 10 patients (10/58, 17.2%) showed CRLF2 over-expression. There were statistical differences in age, WBC count, immunophenotypes, cytogenetics and risk stratification among Ph-like fusion gene positive or CRLF2 over-expression patients, Ph⁺ patients, MLL⁺ patients and B-other patients. The 2-year overall survival rates were 65%, 47%, 64% and 74% respectively among these four groups (P=0.043) . The 2-year relapse free survival rates were 51%, 39%, 62% and 70% respectively among these four groups (P=0.010) . Conclusion Routine screening of Ph-like ALL by multiplex RTPCR is feasible.

Objective To observe the effects of wild jujube seed decoction (WJSD) on learning memory and the levels of malondialdehyde (MDA) and the activities of supemxide dismutase (SOD) and nitric oxide synthase (NOS) in the brain of the pathogeny model rats with sleep deprivation (SD). Methods Levels of learning memory and MDA, and activities of SOD and NOS in rats' brain were assayed after SD induced by made-self multiple platform method ( MMPM), senescence induced by D-galactose, and Yin and blood-deficiency induced by eyclophosphamide and hydrocortisonum. Results After 48 h SD, the levels of learning memory was lower in the model group( ( 108.9 ± 12.5 ) s, ( 89 ± 11.5 ) s, ( 0 ) ) than those in the environmental control group ( ( 47.3 ±4.6)s,(9±1.4)s,(6.5 ±1.2))(( t=4.36,3.18,2.07, P＜0.01＝＝. While MDA, and activities of SOD and NO in rats'brain higher in the model group( (3.8 ±0.6) ,(3.0 ±0.5)nmol · mgprot-1 ,(229.7 ±25.8) ,(236.3± 25.2 ) U · mgprot - 1, ( 5.7 ± 0. 8 ), ( 5.4 ± 0.9 ) U · mgprot - 1 ) than those in the environmental control group ( (2. 1 ±0.4) ,(1.6 ±0.4)nmol · mgprot-1 ,(155.5 ±10.6) ,( 147.2 ±26.1 )U · mgprot-1 ,(2.8 ±0.7),(2.9 ± 0.5 ) U · mgprot -1 ) ( t = 2.89,3.01,6.78,5.94,3.10,3.46, P ＜ 0.05 ＝. However, the observation of the groups treated with WJSD, the levels of learning memory showed a tendency in returning to normal level (P ＜ 0.05 ＝ ,and MDA, and activities of SOD and NO of the high dose of WJSD showed a tendency in returning to normal leve1 (P ＜ 0.05 ＝ ,and the low dose of WJSD showed a tendency in returning to normal level too(P ＜ 0.05 ＝. Conclusion WJSD can improve the disability of learning and memory of the pathogeny rats model, and its one of mechanism maybe involve the reduction of neural cell damage with free radical and NO.

Objective To observe the effects of wild jujube seed decoction(WJSD) on ultrastructure and astrocytes expression in the brain cortex of old model rats with blood-deficiency and Yin and sleep deprivation(SD)after SD. Methods Ultrastructural changes in cortical parts of the experiment rat were observed by transmission electron microscopy , immunohistochemical staining was used to detect star-shaped glial cells marker-glial fibrillary acidic protein(GFAP) expression after SD induced by made-self multiple platform method (MMPM), senescence induced by D-galactose, and Yin and blood-deficiency induced by cyclophosphamide and hydrocortisonum. Results Compared to environmental control group((9.8 ± 2.5), (0.11 ± 0.02) ) , syndrome model group (( 20.4 ±4.4), (0.20 ±0.011) ) rats had obvious ultrastructural changes and stronger expression of GFAP in cortical parts (t = 7.63,3.18, P ＜ 0. 01), while those of W J SD of high and low dose group ((14.4 ± 3.9), (15.5 ± 6.4),(0.14 ±0.02)(0.14±0.02)) rats showed weaker(t=6.32,5.24,2.31,2.45, P＜0.05). Conclusion WJSD of large and small lose group could improve the rats neurons pathological changes,WJSD downward adjusting the expression of GFAP may be one of the mechanisms of treatment on insomnia with blood-deficiency and Yin in the old.