BackgroundThe mortality of cervical cancer in Longnan is as high as 39/10 million, ranking first in China.MethodsBetween 2012 to 2016, 329 samples with cervicitis, cervical intraepithelial neoplasia grade 1 to 3 (CINI to III), and invasive squamous cell carcinoma (SCC) were collected. HPV genotypes were examined with a validated kit for 23 different HPV subtypes.ResultsCompared to cervicitis, the HPV positivity is significantly higher in CINI, CIN II/III, and SCC (38.60%, 74.60%, 87.50% and 89.05%, P < 0.001) and the positivity is also higher in SCC compared to CINI (P < 0.01). The most frequently detected genotypes were HPV16 in cervicitis, HPV16, 58 and 52 in CINI and CIN II/III, and HPV16, 58 and 18 in SCC groups. HPV16 positivity in cervicitis, CINI, CIN II/III, and SCC patients were 45.46%, 46.81%, 60.32% and 78.69%, respectively. Compared to cervicitis and CINI, the odds ratios (OR) for SCC in HPV16 positive patients were 2.96 (95% confidence interval [CI]: 1.09–8.00, P < 0.05) and 4.20 (95% confidence interval [CI]: 2.05–8.61, P < 0.001), respectively. In addition, the multiple infections in cervicitis, CINI, CINII/III and SCC group are 9.09%, 27.66%, 26.98% and 25.41% and HPV16 + 58 was the most common combinations.ConclusionThese findings highlight the key role of HPV16, 58, 52 and 18 in the development of CIN and SCC in Longnan women and a fully aware of regional differences in HPV genotype distribution are tasks for cervical cancer control and prevention.
Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal cell apoptosis. The antisense RNA of brain-derived neurotrophic factor (BDNF-AS) is a natural antisense transcript that is transcribed opposite the gene that encodes BDNF. The aim of this study was to determine whether knockdown of BDNF-AS can suppress hypoxia/reoxygenation (H/R)-induced neuronal cell apoptosis and whether this is mediated by the BDNF-TrkB-PI3K/Akt pathway. We detected the expression of BDNF and BDNF-AS in brain tissue from 20 patients with cerebral infarction and five patients with other diseases (but no cerebral ischemia). We found that BDNF expression was significantly downregulated in patients with cerebral infarction, whereas the expression of BDNF-AS was significantly upregulated. In both human cortical neurons (HCN2) and human astrocytes, H/R significantly induced the expression of BDNF-AS, but significantly decreased BDNF expression. H/R also significantly induced apoptosis and reduced the mitochondrial membrane potential in these cells. Following downregulation of BDNF-AS by siRNA in human cortical neurons and human astrocyte cells, BDNF expression was significantly upregulated and the H/R-induced upregulation of BDNF-AS was significantly attenuated. BDNF-AS siRNA inhibited H/R-induced cell apoptosis and ameliorated the H/R-induced suppression of mitochondrial membrane potential. H/R inhibited the expression of BDNF, p-AKT/AKT, and TrKB, and this inhibition was recovered by BDNF-AS siRNA. In summary, this study indicates that BDNF-AS siRNA induces activation of the BDNF-TrkB-PI3K/Akt pathway following H/R-induced neurotoxicity. These findings will be useful toward the application of BDNF-AS siRNA for the treatment of neurodegenerative diseases.
Parkinson's disease (PD) is a common degenerative disease that lacks efficient treatment. Myelin-associated neurite outgrowth inhibitor A (Nogo-A) is relevant with inhibition of nerve regeneration and may play vital role in pathogenesis of PD. The study aimed to establish the shRNA expression plasmids of Nogo-A gene and explore the regulatory effects of Nogo-A silencing on the expression of inflammation factor tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as tyrosine hydroxylase (TH) in lipopolysaccharide- (LPS-) stimulated rat PC12 cells. The results showed that both mRNA and protein levels of Nogo-A in pGenesil-nogoA-shRNA group were downregulated. The viabilities of PC12 cells decreased with increase of LPS concentrations. LPS significantly increased the supernatant TNF-alpha and IL-6 concentrations and reduced TH protein expression in PC12 cells, while silencing Nogo-A could block these effects. These results suggested that LPS can activate PC12 cells to secrete inflammatory cytokines and lower the TH expression, which can be regulated by Nogo-A gene silencing. Nogo-A silencing might provide new ideas for PD treatment in the future.
BackgroundTumour radiosensitivity would be particularly useful in optimizing the radiation dose during radiotherapy. The aim of the current study was to evaluate the potential value of phosphorylated H2AX (γH2AX) and ATM (pATM) in assessing 12C6+ radiosensitivity of tumour cells.MethodsHuman cervical carcinoma HeLa cells, hepatoma HepG2 cells, and mucoepidermoid carcinoma MEC-1 cells were irradiated with different doses of 12C6+. The survival fraction was assayed with clonogenic survival method and the foci of γH2AX and pATM was visualized using immunocytochemical methods. Flow cytometry was used to assay γH2AX, pATM and the cell cycle.ResultsThe survival fraction decreased immediately in dose-dependent manner, but in turn, significantly increased during 24 h after 12C6+ irradiation. Both γH2AX and pATM foci accumulated linearly with doses and with a maximum induction at 0.5 h for γH2AX and 0.5 or 4 h for pATM, respectively, and a fraction foci kept for 24 h. The expression of γH2AX and pATM was in relation to cell cycle. The G0/G1 phase cells had the highest expression of γH2AX after 0.5 h irradiation and then decreased to a lower level at 24 h after irradiation. An obvious increase of pATM in G2/M phase was shown after 24 h of 2 and 4 Gy irradiation. The significant G2/M phase arrest was shown. There was a close relationship between the clonogenic survival and γH2AX and pATM expression both in timing and dose in response to 12C6+.ConclusionsThe rate of γH2AX and pATM formation and loss may be an important factor in the response of cells to 12C6+. pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of 12C6+ in human tumor cells.
Research on characterizing and optimizing heat-transfer capacity (UA), an important design parameter determining separation efficiency and energy consumption in heat-integrated air separation columns (HIASC), is presented. The mathematical mechanism model of HIASC is built first, then characteristics of UA are explored. It is discovered that on one hand increasing of UA will lead to higher compressor load and thus brings higher energy consumption; however on the other hand increasing of UA will benefit mass transfer and conversely reduces energy consumption. For this reason, the optimal design on UA makes available the maximum energy efficiency together with considerable savings of the equipment investment, which provides guidelines for further designing of HIASC. Furthermore, an optimal partially coupled structure of HIASC is developed to exploit energy saving potential by lowering minimum temperature difference. The obtained optimization results show that the optimal design of UA for a fully coupled HIASC has achieved a 41.5% reduction in energy consumption compared to conventional air separation columns (CASCs) and up to 46.9% energy reduction is achieved by applying the optimal partially coupled design.
ObjectiveTo evaluate the safety and efficacy of removing blood stasis (RBS) herbal medicine for the treatment of acute intracerebral haemorrhage (AICH) within a 6-hour time window.Study designA randomised, multicentre, double-blind, placebo-controlled study performed in 14 hospitals in China.Participants and interventionsPatients with AICH were randomly assigned to receive a placebo, the ICH-1 (Intracerebral Haemorrhage) formula (eight herbs, including the RBS herbs hirudo and tabanus) or the ICH-2 formula (six herbs without the RBS herbs hirudo and tabanus) within 6 hours of ICH onset.OutcomesThe primary safety outcome was the incidence of haematoma enlargement at 24 hours and at 10 days after treatment. The secondary outcome was the incidence of poor prognosis (mortality or modified Rankin Scale score ≥5) assessed at 90 days after symptom onset.ResultsA total of 324 subjects were randomised between October 2013 and May 2016: 105 patients received placebo; 108 patients received the ICH-1 formula; and 111 patients received the ICH-2 formula. The incidence of haematoma enlargement at 24 hours was 7.8% in the placebo group, 12.3% in the ICH-1 group and 7.5% in the ICH-2 group; the incidence of haematoma enlargement on day 10 was 1.1% in the placebo group, 1.1% in the ICH-1 group, and 3.1% in the ICH-2 group, with no significant differences among the groups (P>0.05). The mortality rates were 3.8% in the placebo group, 2.8% in the ICH-1 group, and 0.9% in the ICH-2 group; the incidences of poor prognosis were 7.1% in the placebo group, 6.0% in the ICH-1 group and 4.8% in the ICH-2 group at 3 months, with no significant differences among the groups (p>0.05). However, the overall frequency of treatment-emergent adverse events in the ICH-1 group (12.1%) was higher among the three groups (5.8% and 2.8%, respectively, p<0.05). All three cases of serious adverse events were in the ICH-1 group.ConclusionsUltra-early administration of ICH-1 formula for AICH patients did not exert significant beneficial effects on clinical outcomes but increased the risk of bleeding, which probably resulted from the inclusion of RBS herbal medicines in ICH-1.Trialregistration numberNCT01918722.
ObjectiveIn this study, we aimed to explore the alterations in gut microbiota composition and cytokine responses related to disease progression, severity, and outcomes in patients with hypertensive intracerebral hemorrhage (ICH).MethodsFecal microbiota communities of 64 patients with ICH, 46 coronary heart disease controls, and 23 healthy controls were measured by sequencing the V3-V4 region of the 16S ribosomal RNA (16S rRNA) gene. Serum concentrations of a broad spectrum of cytokines were examined by liquid chips and ELISA. Relationships between clinical phenotypes, microbiotas, and cytokine responses were analyzed in the group with ICH and stroke-associated pneumonia (SAP), the major complication of ICH.ResultsIn comparison with the control groups, the gut microbiota of the patients with ICH had increased microbial richness and diversity, an expanded spectrum of facultative anaerobes and opportunistic pathogens, and depletion of anaerobes. Enterococcus enrichment and Prevotella depletion were more significant in the ICH group and were associated with the severity and functional outcome of ICH. Furthermore, Enterococcus enrichment and Prevotella depletion were also noted in the SAP group in contrast to the non-SAP group. Enterococci were also promising factors in the prognosis of ICH. The onset of ICH induced massive, rapid activation of the peripheral immune system. There were 12 cytokines (Eotaxin, GM-CSF, IL-8, IL-9, IL-10, IL-12p70, IL-15, IL-23, IL-1RA, IP-10, RANTES, and TNF-α) changed significantly with prolongation of ICH, and the Th2 responses correlated with the 90-day outcomes. Cytokines TNF-α, IP-10, IL-1RA, IL-8, IL-18, and MIP-1β in SAP group significantly differed from non-SAP group. Among these cytokines, only IP-10 levels decreased in the SAP group. Enterococcus was positively associated with IL-1RA and negatively associated with IP-10, while Prevotella was inversely associated in both the ICH and SAP groups.ConclusionThis study revealed that gut dysbiosis with enriched Enterococcus and depleted Prevotella increased the risk of ICH and subsequently SAP. The altered gut microbiota composition and serum cytokine profiles are potential biomarkers that reflect the inciting physiologic insult/stress involved with ICH.
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