[Efficacy evaluation of novel oral anticoagulants in patients with cirrhosis accompanied with portal vein thrombosis: a meta-analysis].

Objective: To analyze the safety and efficacy of using novel oral anticoagulants (rivaroxaban and others) in patients with cirrhosis accompanied with portal vein thrombosis (PVT). Methods: Clinical research literature published from the establishment of the database to June 20, 2021, was retrieved from PubMed, Web of Science, CNKI, Wanfang, and Weipu databases by combining subject terms and free words. RevMan software was used for the random group meta-analysis model. Results: In terms of PVT recanalization, the novel oral anticoagulants (such as low molecular weight heparin and others) had a higher recanalization rate than traditional anticoagulants (OR = 13.75, 95%CI 3.58-52.9, P = 0.000 1). In terms of bleeding, the novel oral anticoagulants did not increase the risk of bleeding compared with traditional anticoagulants (OR = 2.42, 95%CI 0.62-9.41, P = 0.20). Conclusion: The novel oral anticoagulant drugs are superior to traditional anticoagulants in terms of the occurrence of PVT recanalization; however, there is no statistically significant difference in terms of the occurrence of bleeding between the two groups.

[Three-dimensional volume rendering for dynamic characteristics of secundum atrial septal defect during various phases of the cardiac cycle and the impact on occluder selection].

Objective: To investigate the dynamic change of the secundum atrial septal defect (ASD) throughout the cardiac cycle, and assess its impact on occluder selection. Methods: This study retrospectively analyzed 35 patients with ASD who received electrocardiogram-gated coronary CT angiography (CCTA) throughout the cardiac cycle as well as interventional closure therapy in Fuwai Hospital from December 2016 to December 2019. The raw data were reconstructed into 20 phasic images of RR intervals (RRI) ranging from 0 to 95% in an increment of 5% and transmitted to a workstation for postprocessing. For each phase image, CT virtual endoscopy reconstruction technique (CTVE) was used to provide views of ASD. Axial sequence assisted CT volumetric measurement (CTAS) was used to calculate the maximum dimensions in axial planes (Da) and in superior-inferior direction (Db). Using a formula for converting circumference to diameter, the equivalent circle dimensions were calculated (De, De=minor axis+2 (major axis-minor axis)/3). Taking the data of 75% RRI phase, the patients were divided into Da75%RRI≥Db75%RRI group and Da75%RRIDa. Db is basically constant while Da changes significantly during cardiac cycle (10%-90% RRI). Nonetheless, both values peak and maintain the maximum status at end-systolic phase (35%-45% RRI). For patients with huge ASD, occluder selection should be based on the De at 35% RRI phase, which is helpful for the successful intervention.

[Berberine protects myocardial injury and cardiac dysfunction in a septic rat model].

Objectives: To investigated whether berberine could ameliorate septic cardiomyopathy in a rat model of sepsis and it's mechanisms. Methods: SD rats were divided into 3 groups: sepsis group (LPS group), rats were intraperitoneal injected of LPS (10 mg/kg); Berberine intervention group (Ber group), Ber (50 mg/kg, one time per day) was gavage fed 3 days before intraperitoneally injection of lipopolysaccharides (LPS); control group (Con group), rats were gavage fed with double distilled water (2 ml/100 g, one time per day) 3 days before intraperitoneal injection of normal saline (1 ml/100 g). LPS group and the Ber group was further divided into 3 subgroups (n=6), and the follow-up experiments were conducted at 6 h, 24 h and 48 h after LPS injection (of which 48 h subgroup rats were gavage fed with Ber/saline at 24 h). Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and the maximum rate of change of left ventricular pressure (±dp/dtmax) were monitored, the level of cardiac troponin T (cTnT), tumor necrosis factor (TNF)-α and interleukin (IL)-1ß was detected by ELISA method, HE staining of myocardial tissues was done to observe myocardial injury; Western blotting method was used to detect the expression of toll-like receptor 4(TLR4) protein in rat myocardial tissue, the level of myocardial cell nucleus protein p65 was detected to reflects the degree of NF-κB activation. The correlation of factors was analyzed with Pearson correlation analysis. Results: Pre-treatment with berberine stabilized cardiac hemodynamics and improved the systolic function and diastolic function in the heart of LPS-induced rats, as evidenced by the partial recovery of the reduced±dp/dtmax and LVSP, as well as the decreased LVEDP. Compared with the LPS group, the Ber group showed improved myocardial injury, as demonstrated by decreased cTnT at each time point. HE staining results showed that berberine decreased inflammatory cell infiltration and LPS-induced cell swelling. These effects were observed early at 6 hours, severe at 24 hours, and become more serious at 48 hours after LPS injection. Further, TLR4 and NF-κB p65 subunits, which were the two key factors of the TLR4/NF-κB signaling, were upregulated in the LPS group and attenuated in the Ber group. Consistently, the expression levels of the downstream cytokines TNF-α and IL-1ß were lower in the Ber group than those in the LPS group (all P<0.05). Myocardial injury markers were positively correlated with the markers of TLR4/NF-κB signals and the downstream host inflammatory factors (all P<0.05). Conclusions: Berberine can improve myocardial injury and cardiac function in sepsis rats, the mechanism is considered to be related to that it can inhibit the activation of TLR4/NF-κB signaling pathway induced by LPS and further reducing the production of TNF-α and IL-1ß.

[Clinical characteristics of patients with Klebsiella pneumoniae pyogenic liver abscess].

Objective: To summarize the clinical features of patients with Klebsiella pneumoniae pyogenic liver abscess(KP-PLA). Methods: Clinical data of 133 patients with pyogenic liver abscess(PLA) and positive results of blood or pus culture were retrospectively analyzed in Huashan Hospital Affiliated to Fudan University from 2009 to 2018. According to the culture results, patients were divided into KP-PLA group (n=92) and non-KP-PLA group (n=41). Results: KP-PLA and non-KP-PLA were similar in gender composition with males accounting for 67.39% and 70.73%, and had age of (56.8±13.8) years and (55.0±13.0) years (χ(2)=0.146, 0.708, P>0.05) respectively. The underlying diseases were more common in KP-PLA group, including diabetes accounting for 45.65% and 24.39%, and hypertension accounting for 32.61% and 14.63% (χ(2)=5.384, 4.642, P<0.05) respectively. Patients with KP-PLA had more invasive infections beyond liver than those with non-KP-PLA, which were 27.17% and 9.76% (χ(2)=5.046, P=0.025). The laboratory results showed that hemoglobin levels in KP-PLA and non-KP-PLA were (109.88±20.97) g/L and (97.75±20.25) g/L (t=3.086, P=0.002). Serum alkaline phosphatase levels were 146.50 (114.50, 237.50) U/L and 220.50 (120.00, 316.75) U/L in KP-PLA and non-KP-PLA (U=2 239.500, P=0.048) patients. Conclusions: KP-PLA mainly develops in middle-aged and elderly men, especially those with diabetes and hypertension. Patients with KP-PLA need to be paid more attention for invasive manifestations beyond liver.

[Analysis of influencing factors of heart rate deceleration capacity in patients with dilated cardiomyopathy].

Objective: To investigate the determinants affecting the heart rate deceleration capacity (DC) in patients with dilated cardiomyopathy (DCM). Methods: One hundred patients with DCM (DCM group) and 202 healthy subjects (control group) were respectively enrolled. Echocardiography and 24 hours electrocardiogram were performed in all subjects. DC value was compared between the two groups. Multiple regression analysis was made to evaluate the related determinants of DC ((age, sex, echocardiographic parameters including the left atrial diameter (LAD) and left ventricular ejection fraction (LVEF)). Results: (1) DC value was significantly lower in DCM group than in control group( (4.40±2.03) ms vs. (7.30±1.81) ms, P<0.01), prevalence of DC value≤4.5 ms was significantly higher in DCM group than in control group (62% vs. 6%, P<0.01). (2) DC value in the DCM group decreased in proportion to increasing LAD dimension, DC value was (5.60±2.04) ms, (4.50±2.07) ms and (3.60±1.62) ms (P<0.05) in DCM patients with LAD≤40 mm, 40 mm50 mm, respectively. (3) DC value in the DCM group was negatively related to the LAD (r=-0.366, P<0.01), positively related to the LVEF (r= 0.241, P<0.01), but not related with age and sex. Multiple factors regression analysis showed that increased LAD was related to the reduced DC values independtly. Conclusion: DC value of the patients in the DCM group is decreased, which indicate the decrease of the vagus nerve tension, and increased LAD is related to the reduced DC value independtly in DCM patients.

The SNP-set based association study identifies ITGA1 as a susceptibility gene of attention-deficit/hyperactivity disorder in Han Chinese.

Genome-wide association studies, which detect the association between single-nucleotide polymorphisms (SNPs) and disease susceptibility, have been extensively applied to study attention-deficit/hyperactivity disorder (ADHD), but genome-wide significant associations have not been found yet. Genetic heterogeneity and insufficient genomic coverage may account for the missing heritability. We performed a two-stage association study for ADHD in the Han Chinese population. In the discovery stage, 1033 ADHD patients and 950 healthy controls were genotyped using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Infinium HumanExome BeadChip. The genotyped SNPs were combined to generate a powerful SNP set with better genomic coverage especially for the nonsynonymous variants. In addition to the association of single SNPs, we collected adjacent SNPs as SNP sets, which were determined by either genes or successive sliding windows, to evaluate their synergetic effect. The candidate susceptibility SNPs were further replicated in an independent cohort of 1441 ADHD patients and 1447 healthy controls. No genome-wide significant SNPs or gene-based SNP sets were found to be associated with ADHD. However, two continuous sliding windows located in ITGA1 (P-value=8.33E-7 and P-value=8.43E-7) were genome-wide significant. The quantitative trait analyses also demonstrated their association with ADHD core symptoms and executive functions. The association was further validated by follow-up replications for four selected SNPs: rs1979398 (P-value=2.64E-6), rs16880453 (P-value=3.58E-4), rs1531545 (P-value=7.62E-4) and rs4074793 (P-value=2.03E-4). Our results suggest that genetic variants in ITGA1 may be involved in the etiology of ADHD and the SNP-set based analysis is a promising strategy for the detection of underlying genetic risk factors.

[Expression changes of Notch and nuclear factor-κB signaling pathways in the rat heart with myocardial infarction].

Objective: To observe the expression changes of Notch and nuclear factor-κB (NF-κB) signaling pathways in rat myocardium post myocardial infarction. Methods: Myocardial infarction was established by ligation of the left anterior descending coronary artery(MI group), sham rats (similar surgical procedure without coronary artery ligation) served as control, the rats were sacrificed at first week, 4th and 8th week after operation, the non-infarct myocardial tissue in both groups was obtained to detect the mRNA expression of Notch1, Dll4 and Hes1 by RT-PCR, the protein expression of NICD1 was detected by Western blot, the nuclear protein p65 content was detected to reflect the activation degree of NF-κB signaling in the cardiomyocytes. Results: The myocardial mRNA expression of Notch1 in MI group was significantly higher than in control group (1.68±0.35 vs. 0.47±0.12, P<0.05) at first week, and tended to be higher at the 4th week and 8th week (P>0.05). The mRNA expression of Dll4 and Hes1 was similar between the two groups at the three time points. NICD1 protein level was increased at the first week in MI group as compared with control group (1.31±0.33 vs.0.45±0.11, P<0.05), which tended also to be higher at the 4th week and 8th week post operation (P>0.05). For NF-κB activation study, the nuclear protein p65 content was higher at first week, 4th week and 8th week in MI group as compared with respective control groups (0.286±0.052 vs.0.049±0.016 (P<0.01), 0.247±0.056 vs. 0.043±0.018 (P<0.01), 0.120±0.033 vs. 0.044±0.009 (P<0.05)), the most significant increase was found in the first week. Conclusions: Notch and NF-κB signaling pathways are actively involved in the process of ventricular remodeling after myocardial infarction. Notch1 and NF-κB signaling pathways are both activated at the first week after myocardial infarction, NF-κB signaling pathway activation after myocardial infarction continues up to 8 weeks. These two signal transduction pathways may thus serve as new targets for future intervention studies to prevent heart failure.

Using hydrological simulation to detect human-disturbed epoch in runoff series.

Runoff in major rivers in China has been decreasing in recent decades, mainly due to climate change and human activity. River basin managers have a critical interest in detecting and diagnosing non-stationaries in runoff time series. Here we use a rainfall runoff model-based approach to identify the human-disturbed periods of the record. The method is applied to the Kuye River catchment, located in the Loess Plateau, China. The SimHyd model performs well for simulation of monthly natural discharges, and the method suggests that discernable human influence began in 1980. Anthropogenic effects were detectable several years earlier at the downstream stations than the upstream stations, consistent with pace and timing of soil and water conservation measures implemented across the Kuye River catchment.

MTBDRplus results correlate with treatment outcome in previously treated tuberculosis patients.

BACKGROUND: Although MTBDRplus is validated for the detection of multidrug-resistant tuberculosis (MDR-TB), its role in the assessment of treatment outcome is less clear. We evaluated the association of MTBDRplus results with treatment outcome in new and previously treated patients in an endemic setting in China and determined factors associated with poor treatment outcomes. METHODS: We prospectively enrolled 298 smear-positive pulmonary TB patients who received the World Health Organization recommended initial treatment regimen or retreatment regimen. MTBDRplus was compared with conventional drug susceptibility testing and DNA sequencing for the detection of MDR-TB. Treatment responses were monitored using sputum smear, culture and chest radiography. RESULTS: MTBDRplus successfully identified all MDR-TB and had good concordance with sequencing. MDR-TB rates were low among new patients (4/187, 2.1%), but high in previously treated patients (12/28, 42.9%); 65.2% (15/23) of previously treated cases and 17.1% (27/158) of new cases were unsuccessfully treated (P < 0.001). Seven of eight (87.5%) previously treated MDR-TB patients failed the retreatment regimen. In addition to drug resistance, sputum smear positivity at week 8 and cavitation are associated with treatment failure. CONCLUSION: Not only did MTBDRplus correctly identify all MDR-TB cases, MTBDRplus results are also associated with treatment outcomes in previously treated patients. The retreatment regimen should no longer be used; treatment should be guided by molecular testing.

Icariin promotes histone acetylation and attenuates post-stroke cognitive impairment in the central cholinergic circuits of mice.

Post-stroke dementia (PSD) is a common clinical disease and the central cholinergic circuits are important to cognitive function. Icariin (ICA), a flavonoid isolated from Herba Epimedii, was reported to improve cognitive function through modulating the cholinergic system. But there were no studies exploring the role of ICA in PSD animal models. In this study, we used transient middle cerebral artery occlusion mice with cognitive dysfunction in the PSD model. PSD mice were then randomly divided into six groups: Sham-operated+placebo group, Sham-operated+ICA group (60mg/kg), PSD model+placebo group, PSD model+ICA group (30, 60, or 120mg/kg). We observed spatial learning ability and memory by Morris water maze test. The levels of acetylcholine (ACH) and choline acetyltransferase (ChAT), the degree of histone acetylation and the cAMP response element-binding protein (CREB) phosphorylation in the central cholinergic circuits were investigated by Western blot and immunofluorescence. After the administration of various doses of ICA, the escape latency and searching distance of the PSD mice were reduced significantly compared with those without ICA treatment. While the levels of ACH and ChAT declined, the degree of histone acetylation and the CREB phosphorylation was improved in a dose-dependent manner in central cholinergic circuits. In conclusion, ICA can improve post-stroke dementia, and the mechanism is likely to enhance CREB phosphorylation in the central cholinergic circuits, thus improving the damage in cholinergic circuits histone acetylation homeostasis.

Correlation of Y-chromosome multiple segmental deletions and chromosomal anomalies in non-obstructive azoospermic males from northeastern China.

We investigated the frequency and types of Y-chromosome microdeletions and chromosomal anomalies in non-obstructive azoospermic and severely oligozoospermic infertile males in northeastern China. The sample consisted of 519 infertile males (456 azoospermic, 63 severely oligozoospermic). PCR assays for Y-chromosome microdeletions and chromosome analysis were performed on all patients and controls. Array-comparative genomic hybridization was performed for three patients with chromosomal anomalies. Fifty-nine of 519 patients (11.37%) had Y-chromosome microdeletions. Microdeletions were found in 11.18% (51/456) of the non-obstructive azoospermic patients and in 12.7% (8/63) of the severely oligozoospermic patients. Eleven of 51 non-obstructive azoospermic patients with Y-chromosome microdeletions had multiple segmental deletions in the AZFb+c regions; four of these patients had chromosomal anomalies. Our sample from northeastern China had a higher frequency of microdeletions among severely oligozoospermic than among non-obstructive azoospermic males.

[A preliminary study on mechanism of respiratory deficiency of mutagenesis in S. cerevisiae].

The results of ethidium bromide treatment for two different strains of S. cerevisiae were reported here. The recovery of respiratory competence was discovered when cells were treated with EB under non-growing condition. However, this recovery can be inhibited by caffeine. It was not observed when cells were treated with EB under growing condition. Similar results were obtained when cells were treated with EB during their exposure to KCN. The formation of at least one intermediate state [rho-] was proposed. The process of formation of respiratory deficiency could be expressed by rho+ in equilibrium [rho-]----rho-. The different concentrations of sucrose supplemented to the culture of S. cerevisiae resulted in certain influence in the experiment.