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BackgroundThe timing of surgery for aortic stenosis (AS) is imperfect, and the management of moderate AS and asymptomatic severe AS is still challenging. Myocardial fibrosis (MF) is the main pathological basis of cardiac decompensation in patients with AS and can be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to evaluate the prognostic value of MF measured by CMR in patients with AS, which can provide a reference for the timing of aortic valve replacement (AVR).MethodsWe searched Medline, Embase, and Web of Science to include all studies that investigated the prognostic value of CMR in patients with AS. The search deadline is March 31, 2021. The pooled relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (CI) of the biomarkers including late gadolinium enhancement (LGE), Native T1 or extracellular volume (ECV) were calculated to evaluate the prognostic value.Results13 studies and 2,430 patients with AS were included in this study, the mean or medium follow-up duration for each study was ranged from 6 to 67.2 months. Meta-analysis showed the presence of LGE was associated with an increased risk for all-cause mortality (pooled RR: 2.14, 95% CI: 1.67-2.74, P < 0.001), cardiac mortality (pooled RR: 3.50, 95% CI: 2.32-5.30, P < 0.001), and major adverse cardiovascular events (MACEs) (pooled RR: 1.649, 95% CI: 1.23-2.22, P = 0.001). Native T1 was significantly associated with MACEs (pooled RR: 2.23, 95% CI: 1.00-4.95; P = 0.049), and higher ECV was associated with a higher risk of cardiovascular events (pooled HR: 1.69, 95% CI: 1.11-2.58; P = 0.014).ConclusionThe use of CMR to detect MF has a good prognostic value in patients with AS. LGE, Native T1 and ECV measured by CMR can contribute to risk stratification of AS, thereby helping to optimize the timing of AVR.

According to the forest resources inventory data for different periods and the latest estimation parameters of forest carbon reserves in China, the carbon reserves and carbon density of forest biomass in the Tibet Autonomous Region from 1999 to 2019 were estimated using the IPCC international carbon reserves estimation model. The results showed that, during the past 20 years, the forest area, forest stock, and biomass carbon storage in Tibet have been steadily increasing, with an average annual increase of 1.85×104 hm2, 0.033×107 m3, and 0.22×107 t, respectively. Influenced by geographical conditions and the natural environment, the forest area and biomass carbon storage gradually increased from the northwest to the southeast, particularly in Linzhi and Changdu, where there are many primitive forests, which serve as important carbon sinks in Tibet. In terms of the composition of tree species, coniferous forests are dominant in Tibet, particularly those containing Abies fabri, Picea asperata, and Pinus densata, which comprise approximately 45% of the total forest area in Tibet. The ecological location of Tibet has resulted in the area being dominated by shelter forest, comprising 68.76% of the total area, 64.72% of the total forest stock, and 66.34% of the total biomass carbon reserves. The biomass carbon storage was observed to first increase and then decrease with increasing forest age, which is primarily caused by tree growth characteristics. In over-mature forests, trees' photosynthesis decreases along with their accumulation of organic matter, and the trees can die. In addition, this study also observed that the proportion of mature and over-mature forest in Tibet is excessively large, which is not conducive to the sustainable development of forestry in the region. This problem should be addressed in future management and utilization activities.

Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls, and to test the performance of plasma ADTRP as a biomarker for CAD. We measured plasma ADTRP, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high sensitivity-C reactive protein (hs-CRP) levels in 362 CAD patients, 150 angiographically negative CAD controls, and 83 healthy adults with no known clinical or medical conditions using commercial ELISA. Statistical analyses were performed using receiver operator characteristic (ROC) curves, quantile regression and logistic regression, with adjustments for age, gender, ethnicity and BMI. CAD patients had significantly lower plasma ADTRP levels 1,545 (1,087-2,408) pg/ml as compared to CAD controls 2,259 (1,533-3,778) pg/ml and healthy adults 3,904 (2,732-5,463) pg/ml. Plasma ADTRP outperformed the other three inflammatory biomarkers (TNF-α, IL-6 and hs-CRP) for CAD (Area under ROC curve: 0.67, Odds ratio (OR): 0.907). Our study has shown for the first time that ADTRP is present in circulation, and that plasma ADTRP may be a novel independent biomarker for CAD.

Previous surveys of neonatal medicine in China have not collected comprehensive information on workforce, investment, health care practice, and disease expenditure. The goal of the present study was to develop a national database of neonatal care units and compare present outcomes data in conjunction with health care practices and costs. We summarized the above components by extracting data from the databases of the national key clinical subspecialty proposals issued by national health authority in China, as well as publicly accessible databases. Sixty-one newborn clinical units from provincial or ministerial hospitals at the highest level within local areas in mainland China, were included for the study. Data were gathered for three consecutive years (2008-2010) in 28 of 31 provincial districts in mainland China. Of the 61 newborn units in 2010, there were 4,948 beds (median = 62 [IQR 43-110]), 1,369 physicians (median = 22 [IQR 15-29]), 3,443 nurses (median = 52 [IQR 33-81]), and 170,159 inpatient discharges (median = 2,612 [IQR 1,436-3,804]). During 2008-2010, the median yearly investment for a single newborn unit was US$344,700 (IQR 166,100-585,800), median length of hospital stay for overall inpatient newborns 9.5 (IQR 8.2-10.8) days, median inpatient antimicrobial drug use rate 68.7% (IQR 49.8-87.0), and median nosocomial infection rate 3.2% (IQR1.7-5.4). For the common newborn diseases of pneumonia, sepsis, respiratory distress syndrome, and very low birth weight (

Indigenous populations globally are disproportionately affected by chronic hepatitis B virus (HBV) infection however contemporary sero-prevalence data are often absent. In the Indigenous population of the Northern Territory (NT) of Australia the unique C4 sub-genotype of HBV universally circulates. There are no studies of the sero-prevalence, nor the impact of the vaccination program (which has a serotype mismatch compared to C4), at a population-wide level.We examined all available HBV serology results obtained from the three main laboratories serving NT residents between 1991 and 2011. Data were linked with a NT government database to determine Indigenous status and the most recent test results for each individual were extracted as a cross-sectional database including 88,112 unique individuals. The primary aim was to obtain a contemporary estimate of HBsAg positivity for the NT by Indigenous status.Based on all tests from 2007-2011 (35,633 individuals), hepatitis B surface antigen (HBsAg) positivity was 3·40% (95%CI 3·19-3·61), being higher in Indigenous (6·08%[5·65%-6·53%]) than non-Indigenous (1·56%[1·38%-1·76%]) Australians, p

The human salivary (AMY1) gene, encoding salivary α-amylase, has variable copy number variants (CNVs) in the human genome. We aimed to determine if real-time quantitative polymerase chain reaction (qPCR) and the more recently available Droplet Digital PCR (ddPCR) can provide a precise quantification of the AMY1 gene copy number in blood, buccal cells and saliva samples derived from the same individual.Seven participants were recruited and DNA was extracted from the blood, buccal cells and saliva samples provided by each participant. Taqman assay real-time qPCR and ddPCR were conducted to quantify AMY1 gene copy numbers. Statistical analysis was carried out to determine the difference in AMY1 gene copy number between the different biological specimens and different assay methods.We found significant within-individual difference (p

The technology of virus-based genetic modification in tissue engineering has provided the opportunity to produce more flexible and versatile biomaterials for transplantation. Localizing the transgene expression with increased efficiency is critical for tissue engineering as well as a challenge for virus-based gene delivery. In this study, we tagged the VP2 protein of type 2 adeno-associated virus (AAV) with a 3×FLAG plasmid at the N-terminus and packaged a FLAG-tagged recombinant AAV2 chimeric mutant. The mutant AAVs were immobilized onto the tissue engineering scaffolds with crosslinked anti-FLAG antibodies by N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP). Cultured cells were seeded to scaffolds to form 3D transplants, and then tested for viral transduction both in vitro and in vivo. The results showed that our FLAG-tagged AAV2 exerted similar transduction efficiency compared with the wild type AAV2 when infected cultured cells. Following immobilization onto the scaffolds of PLGA or gelatin sponge with anti-FLAG antibodies, the viral mediated transgene expression was significantly improved and more localized. Our data demonstrated that the mutation of AAV capsid targeted for antibody-based immobilization could be a practical approach for more efficient and precise transgene delivery. It was also suggested that the immobilization of AAV might have attractive potentials in applications of tissue engineering involving the targeted gene manipulation in 3D tissue cultures.

BACKGROUND: To explore the association between serum human epidermal growth factor receptor 2 (HER 2) extracellular domain (ECD) levels and tissue HER 2 status in metastatic gastric cancer. PATIENTS AND METHODS: HER 2 status was retrospectively analyzed in 219 advanced gastric or gastroesophageal junction (GEJ) patients. Serum HER 2 ECD was measured by chemiluminescent assay and tissue HER 2 was assessed by fluorescent in situ hybridisation (FISH) and immunohistochemistry (IHC) assay. RESULTS: Significant associations were found between serum HER 2 ECD levels and tissue HER 2 status. Twenty-four patients had HER 2 ECD levels >16.35 ng/mL, which has a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER 2 status. When the cut-off value was increased to 22 ng/mL, then all 12 patients with serum HER 2 ECD levels>22 ng/mL were tissue HER 2 positive, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER 2 ECD levels were strongly associated with the intestinal histological type (Lauren's classification), liver metastasis, multiple metastasis (>2) and increased LDH levels, but not with overall survival. CONCLUSIONS: The high specificity of the serum HER 2 ECD assay in predicting tissue HER 2 status suggests its potential as a surrogate marker of the HER 2 status in gastric cancer.

The present study seeks to investigate the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-κB) activation and excitotoxicity in rats striatal neurons. Stereotaxic administration of the N-methyl-d-aspartate (NMDA) receptor agonist Quinolinic acid (QA) into the unilateral striatum was used to produce the in vivo excitotoxic model. Co-administration of QA and the cathepsin L inhibitor Z-FF-FMK or 1-Naphthalenesulfonyl-IW-CHO (NaphthaCHO) was used to assess the contribution of cathepsin L to QA-induced striatal neuron death. Western blot analysis and cathepsin L activity assay were used to assess the changes in the levels of cathepsin L after QA treatment. Western blot analysis was used to assess the changes in the protein levels of inhibitor of NF-κB alpha isoform (IκB-α) and phospho-IκB alpha (p-IκBα) after QA treatment. Immunohistochemical analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced NF-κB. Western blot analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced IκB-α phosphorylation and degradation, changes in the levels of IKKα, p-IKKα, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced loss of striatal neurons were strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced degradation of IκB-α, NF-κB nuclear translocation, up-regulation of NF-κB responsive gene TP53, and activation of caspase-3 was strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced increases in beclin 1, LC3II/LC3I, and down-regulation of p62 were reduced by Z-FF-FMK or NaphthaCHO. These results suggest that cathepsin L is involved in glutamate receptor-induced NF-κB activation. Cathepsin L inhibitors have neuroprotective effects by inhibiting glutamate receptor-induced IκB-α degradation and NF-κB activation.

BACKGROUND: The etiology of birth defects has been widely studied but is not yet fully clarified, previously published data had suggested that maternal age or parity maybe involved, but without consistent conclusions. METHODS: A population-based, case-control study was nested in a cohort of perinatal infants born from 2010 to 2012 in Baoan District, Shenzhen. Four categories of isolated birth defects were defined as cases: congenital heart defects (CHD, n = 693), polydactyly (n = 352), cleft lip with or without palate (CL/P, n = 159) and equinovarus (n = 119). Controls were non-malformed infants (n = 11,307) randomly selected from the same area and period. Odds ratios (ORs) and the 95% confidence intervals (CIs) were computed by multivariable unconditional logistic regression analysis. RESULTS: Young maternal age (

Equine lentivirus receptor 1 (ELR1) has been identified as the sole receptor for equine infectious anemia virus (EIAV) and is a member of the tumor necrosis factor receptor (TNFR) superfamily. In addition to the previously described membrane-associated form of ELR1, two other major alternative splicing variant mRNAs were identified in equine monocyte-derived macrophages (eMDMs). One major spliced species (ELR1-IN) contained an insertion of 153 nt, which resulted in a premature stop codon situated 561 nt upstream of the predicted membrane spanning domain. The other major species (ELR1-DE) has a deletion of 109 nt that causes a shift of the open reading frame and generates a stop codon 312 nt downstream. Because ELR1-DE presumably encodes a peptide of a mere 23 residues, only ELR1-IN was further analyzed. The expression of a soluble form of ELR1 (sELR1) by ELR1-IN was confirmed by Western blot and immunofluorescence analyses. Similar to ELR1, the transcription level of ELR1-IN varied among individual horses and at different time points in the same individuals. The ratio of ELR1-IN mRNA species to ELR1 mRNA was approximately 1∶2.5. Pre-incubation of the recombinant sELR1 with EIAV significantly inhibited EIAV infection in equine macrophages, the primary in vivo target cell of the virus. Fetal equine dermal (FED) cells are susceptible to EIAV in vitro, and the replication of EIAV in FED cells transiently transfected with ELR1-IN was markedly reduced when compared with replication in cells transfected with the empty vector. Finally, the expression levels of both forms of the EIAV receptor were significantly regulated by infection with this virus. Taken together, our data indicate that sELR1 acts as a secreted cellular factor that inhibits EIAV infection in host cells.

Associations between interleukin 6 (IL-6) polymorphisms and Alzheimer's disease (AD) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations for the relationship between IL-6-174 G/C and -572 C/G polymorphisms and risk for AD. Electronic searches for all publications in databases PubMed and EMBASE were conducted on the associations between IL-6 polymorphisms and risk for AD until January 2012. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. Twenty-seven studies were included with a total of 19,135 individuals, involving 6,632 AD patients and 12,503 controls. For IL-6-174 G/C polymorphism, the combined results showed significant differences in recessive model (CC vs. CG+GG: OR = 0.65, 95%CI = 0.52-0.82). As regards IL-6-572 C/G polymorphism, significant associations were shown in dominant model (CG+GG vs. CC: OR= 0.73, 95% CI = 0.62-0.86) and in additive model (GG vs. CC, OR= 0.66, 95% CI = 0.46-0.96). In conclusion, genotype CC of IL-6-174 G/C and genotype GG plus GC of IL-6-572 C/G could decrease the risk of AD.