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A meta-analysis was conducted to evaluate the effect of treatment with angiotensin-converting enzyme inhibitors on the risk of fractures. All the included articleswere retrieved from MEDLINE, EMBASE and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction. Relative risk (RR) with corresponding 95% confidence intervals (95% CI) were used to assess the effect. Six case-control studies with11,387,668 participants met the inclusion criteria and were included in the meta-analysis. A small but significant risk effect on fractures was shown in the overall analysis of angiotensin-converting enzyme inhibitor users compared with nonusers (Pooled RR 1.27; 95% CI 1.01–1.60), although a relatively high heterogeneity was found across studies. In the stratified analysis, therewas no statistically significant association in the subgroups of hip fracture (Pooled RR 1.14; 95% CI 0.73–1.76) and the study quality (Pooled RR 1.13; 95% CI 0.89–1.44), while the over 65-year-old angiotensin-converting enzyme inhibitor users showed a stronger risk effect on fractures (Pooled RR 2.06; 95% CI 1.53–3.17). Moreover, age was found to be contributed a large part of the high heterogeneity across the included studies. This study demonstrated that the use of angiotensin-converting enzyme inhibitors might have a small but significant risk effect on fractures, especially for the over 65-year-old users. These results should be interpreted with caution as the relatively high heterogeneity across studies. Additional multiple observational studies and high quality data from randomized controlled trials are needed to confirm these findings.

Changes of total nitrogen (TN), organic matter, microbial metabolic activity, aerobic denitrifying bacteria and aerobic denitrifying genes (nirS and nirK) in water and surface sediments under mixing aeration were studied in Heihe Jinpen Reservoir. Results showed that compared with the control area, the total nitrogen concentration of water and surface sediments in the enhanced area decreased by 29.7%~49.2% and 17.9%. Metabolic activity of microorganisms increased by more than 14%, the utilization rate of carbon source increased by 30% and the McIntosh diversity index of microorganisms increased by 20%. The number of aerobic denitrifiers and genes of aerobic denitrifiers were also increased by 20%. Illumina high-throughput DNA sequencing results showed that the proportion of aerobic denitrifiers such as Acidovorax increased from 0.01% to 0.15%, showing an increase by 15 times. The production practice showed that mixed aeration can improve the metabolic activity and denitrification characteristics of indigenous aerobic denitrifiers, providing theoretical support and technical guarantee for denitrification and carbon removal of slightly polluted source water.

Purpose Budesonide improves the prognosis of chronic rhinosinusitis (CRS). However, few reports have examined whether its use for nasal irrigation, compared to normal saline, improves the prognosis of patients after endoscopic sinus surgery (ESS). We compared the effects of nasal irrigation with budesonide and normal saline in CRS patients after ESS. Methods Sixty CRS patients who had undergone ESS were randomly divided into an experimental group (30 patients), which used budesonide nasal irrigation, and a control group (30 patients), which used normal saline nasal irrigation. All patients received regular follow-up evaluations and were assessed via questionnaires, including the Lund–Kennedy endoscopic score (LKES), the symptom visual analog scale (VAS), the 22-item Sino-Nasal Outcome Test (SNOT-22), the Short-Form 36-Item Questionnaire (SF-36), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS) and a side effects scale. Results Scores of polyposis, mucosal edema, secretions and total score of LKES; VAS scores of nasal blockage, hyposmia and rhinorrhea; and SNOT-22 results in both groups were significantly improved 3 months after ESS. Scores of polyposis, mucosal edema, secretions and scarring and total score of LKES in experimental group were significantly better than in control group 3 months after ESS. No significant differences were observed in SF-36, SAS or SDS before or 3 months after ESS within or between the two groups. The side effects of the two groups were not significantly different. Conclusions Nasal irrigation improved the prognosis of CRS patients after ESS. Budesonide nasal irrigation had a better effect than normal saline nasal irrigation.

Faced with the problems of hypolimnion dissolved oxygen (DO) depletion and water quality deterioration, a newly designed water quality improvement technology named water-lifting aerators (WLAs) was put into utilization to solve these problems in Jinpen Reservoir. During the hypolimnion oxygenation period, after 20 days operation of 8 WLAs with compressed air volume of 10 m3/h, the thickness of anaerobic layer was compressed from 17 m to 3.2 m. As for artificially induced mixing, after 18 days operation of 8 WLAs with compressed air volume of 50 m3/h (full capacity), the reservoir was mixed, and DO of the bottom water increased to more than 8 mg/L. Removal rates of TN, TP, NH4-N and TOC reached 25.5%, 50%, 29.8% and 19.4% respectively. Results of Biolog method showed that the activity of microbes and carbon source utilization were improved in the water of the controlled area compared with the uncontrolled area during the operation. WLAs have been proved to be an efficient technology in water quality improvement especially in hypolimnion oxygenation and artificially induced mixing.

To report the feasibility, efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for the treatment of portal vein tumor thrombosis (PVTT) and/or inferior vena cava tumor thrombosis (IVCTT) in patients with advanced hepatocellular carcinoma (HCC). Forty-one patients treated with SBRT using volumetric modulated arc therapy (VMAT) for HCC with PVTT/IVCTT between July 2010 and May 2012 were analyzed. Of these, 33 had PVTT and 8 had IVCTT. SBRT was designed to target the tumor thrombosis and deliver a median total dose of 36 Gy (range, 30-48 Gy) in six fractions during two weeks. The median follow-up was 10.0 months. At the time of analysis, 15 (36.6%) achieved complete response, 16 (39.0%) achieved partial response, 7 (17.1%) patients were stable, and three (7.3%) patients showed progressive disease. No treatment-related Grade 4/5 toxicity was seen within three months after SBRT. One patient had Grade 3 elevation of bilirubin. The one-year overall survival rate was 50.3%, with a median survival of 13.0 months. The only independent predictive factor associated with better survival was response to radiotherapy. VMAT-based SBRT is a safe and effective treatment option for PVTT/IVCTT in HCC. Prospective randomized controlled trials are warranted to validate the role of SBRT in these patients.

N6-methyladenosine (m6A) RNA methylation has been shown to have prognostic value in cancer. Nonetheless, its potential role regarding immunity, metabolism, and stemness in soft tissue sarcoma (STS) remains unknown. We comprehensively estimated the m6A modification patterns and corresponding immunity, metabolism, and stemness characteristics based on 568 STS samples and 21 m6A regulators. The m6Ascore was constructed to quantify m6A modification patterns in individuals using machine learning algorithms. Two distinct m6A modification patterns among the STS patients were identified, which exhibited differences in prognosis, immune cell infiltration, metabolic pathways, stemness, somatic mutation, and copy number variation. Thereafter, immunity-, metabolism-, and stemness phenotype-related genes associated with m6A modification were identified. Furthermore, patients with lower m6Ascores had increased antitumor immune responses, survival benefit under immunotherapy, tumor mutation burden, immunogenicity, and response to anti-PD-1/L1 immunotherapy. Immunotherapy sensitivity was validated using the IMvigor210 dataset. STS patients with lower m6Ascore might be more sensitive to docetaxel and gemcitabine. Finally, pan-cancer analysis illustrated the significant correlations of m6Ascore with clinical outcomes, immune cell infiltration, metabolism, and stemness. This study revealed that m6A modification plays an important role in immunity, metabolism, and stemness in STS. Evaluating the m6A modification pattern and development of m6Ascore may help to guide more effective immunotherapy and chemotherapy strategies.

Background Recent observations indicate a decreased cancer risk in patients with Alzheimer’s disease (AD). AD is a severe neurodegenerative disorder characterized by progressive cognitive decline. The 8q24 region has been shown to be involved in AD aetiology. We aimed to identify and explore the potential oncogenes or antioncogenes on chromosome 8q24. Methods We compared expression of genes on Chromosome 8q24 in 32 pairs of samples from The Cancer Genome Atlas (TCGA) database. We conducted bioinformatics analysis of the commonly used gastric cancer databases and performed clinical verification of gastric cancer samples, combined with assessment of biological function both in vitro and in vivo to determine the relationship between upregulated expression of GRINA and gastric cancer progression. We also explored the molecular mechanism of GRINA upregulation and its function in gastric cancer development and progression. Results The expression of GRINA in cancer tissues was significantly higher than that in normal tissues. GRINA indicated poor prognosis in gastric cancer. GRINA promoted the proliferation, migration and invasion capacity of gastric cancer cells. GRINA was transcriptionally mediated by c-Myc and promotes cell cycle transition. GRINA knockdown decreased PI3K/Akt/mTOR signaling and glycolytic metabolism in gastric cancer cells. The apoptosis rate was significantly increased in gastric cancer cell lines after knockdown of GRINA. The expression of pro-apoptotic protein Bax was significantly upregulated, whereas the anti-apoptotic protein Bcl-2 was significantly downregulated in GRINA silenced cells. Conclusions Human gastric cancers have increased levels of GRINA, which promotes growth of gastric cancer and inhibits tumor cells apoptosis.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common and lethal malignant tumors. We aimed to investigate the HNSCC cell differentiation trajectories and the corresponding clinical relevance. Based on HNSCC cell differentiation-related genes (HDRGs) identified by single-cell sequencing analysis, the molecular subtypes and corresponding immunity, metabolism, and stemness characteristics of 866 HNSCC cases were comprehensively analyzed. Machine-learning strategies were used to develop a HNSCC cell differentiation score (HCDscore) in order to quantify the unique heterogeneity of individual samples. We also assessed the prognostic value and biological characteristics of HCDscore using the multi-omics data. HNSCCs were stratified into three distinct molecular subtypes based on HDRGs: active stroma (Cluster-A), active metabolism (Cluster-B), and active immune (Cluster-C) types. The three molecular subtypes had different characteristics in terms of biological phenotype, genome and epigenetics, prognosis, immunotherapy and chemotherapy responses. We then demonstrated the correlations between HCDscore and the immune microenvironment, subtypes, carcinogenic biological processes, genetic variation, and prognosis. The low-HCDscore group was characterized by activation of immunity, enhanced response to anti-PD-1/PD-L1 immunotherapy, and better survival compared to the high-HCDscore group. Finally, by integrating the HCDscore with prognostic clinicopathological characteristics, a nomogram with strong predictive performance and high accuracy was constructed. This study revealed that the cell differentiation trajectories in HNSCC played a nonnegligible role in patient prognosis, biological characteristics, and immune responses. Evaluating cancer cell differentiation will help to develop more effective immunotherapy, metabolic therapy, and chemotherapy strategies.