Association between BCL11B gene polymorphisms and age-related hearing loss in the elderly: A case-control study in Qingdao, China.

Age-related hearing loss is a complex disease caused by a combination of genetic and environmental factors, and a study have conducted animal experiments to explore the association between BCL11B heterozygosity and age-related hearing loss. The present study used established genetic models to examine the association between BCL11B gene polymorphisms and age-related hearing loss. A total of 410 older adults from two communities in Qingdao, China, participated in this study. The case group comprised individuals aged ≥ 60 years with age-related hearing loss, and the control group comprised individuals without age-related hearing loss from the same communities. The groups were matched 1:1 for age and sex. The individual characteristics of the participants were analyzed descriptively using the Mann-Whitney U test and the chi-square test. To explore the association between BCL11B gene polymorphisms and age-related hearing loss, conditional logistic regression was performed to construct genetic models for two single-nucleotide-polymorphisms (SNPs) of BCL11B, and haplotype analysis was conducted to construct their haplotype domains. Two SNP sites of the BCL11B gene, four genetic models of rs1152781 (additive, dominant, recessive, and codominant), and five genetic models of rs1152783 (additive, dominant, recessive, codominant, and over dominant) were significantly associated with age-related hearing loss in the models both unadjusted and adjusted for all covariates (P < 0.05). Additionally, a linkage disequilibrium between rs1152781 and rs1152783 was revealed through haplotype analysis. Our study revealed that BCL11B gene polymorphisms were significantly associated with age-related hearing loss.

Identification of Key Genes and Imbalanced SNAREs Assembly in the Comorbidity of Polycystic Ovary Syndrome and Depression.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have increased odds of concurrent depression, indicating that the relationship between PCOS and depression is more likely to be comorbid. However, the underlying mechanism remains unclear. Here, we aimed to use bioinformatic analysis to screen for the genetic elements shared between PCOS and depression. METHODS: Differentially expressed genes (DEGs) were screened out through GEO2R using the PCOS and depression datasets in NCBI. Protein-protein interaction (PPI) network analysis and enrichment analysis were performed to identify the potential hub genes. After verification using other PCOS and depression datasets, the associations between key gene polymorphism and comorbidity were further studied using data from the UK biobank (UKB) database. RESULTS: In this study, three key genes, namely, SNAP23, VTI1A, and PRKAR1A, and their related SNARE interactions in the vesicular transport pathway were identified in the comorbidity of PCOS and depression. The rs112568544 at SNAP23, rs11077579 and rs4458066 at PRKAR1A, and rs10885349 at VTI1A might be the genetic basis of this comorbidity. CONCLUSIONS: Our study suggests that the SNAP23, PRKAR1A, and VTI1A genes can directly or indirectly participate in the imbalanced assembly of SNAREs in the pathogenesis of the comorbidity of PCOS and depression. These findings may provide new strategies in diagnosis and therapy for this comorbidity.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation.

The fibroblast growth factor receptor (FGFR) signaling pathway plays important roles in cellular processes such as proliferation, differentiation, and migration. In this study, we highlighted the potential of FGFR inhibitors bearing the (S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene scaffold containing a crucial 3-pyridyl group for the treatment of FGFR mutant cancers. The representative compound (S)-23, which was identified through comprehensive evaluation, exhibited potent antiproliferative activity with GI50 in the range of 6.4-10.4 nM against FGFR1 fusion protein-carrying, FGFR2-amplified, and FGFR2 mutant cancer cell lines and good antiproliferative activity against FGFR3 translocation and mutant FGFR4 cancer cell lines, as well as potency assessment against FGFR1-4 kinases. Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.

Exploring the cross-cancer effect of circulating proteins and discovering potential intervention targets for 13 site-specific cancers.

BACKGROUND: The proteome is an important reservoir of potential therapeutic targets for cancer. This study aimed to examine the causal associations between plasma proteins and cancer risk and to identify proteins with cross-cancer effects. METHODS: Genetic instruments for 3991 plasma proteins were extracted from a large-scale proteomic study. Summary-level data of 13 site-specific cancers were derived from publicly available datasets. Proteome-wide Mendelian randomization and colocalization analyses were used to investigate the causal effect of circulating proteins on cancers. Protein-protein interactions and druggability assessment were conducted to prioritize potential therapeutic targets. Finally, systematical Mendelian randomization analysis between healthy lifestyle factors and cancer-related proteins was conducted to identify which proteins could act as interventional targets by lifestyle changes. RESULTS: Genetically determined circulating levels of 58 proteins were statistically significantly associated with 7 site-specific cancers. A total of 39 proteins were prioritized by colocalization, of them, 11 proteins (ADPGK, CD86, CLSTN3, CSF2RA, CXCL10, GZMM, IL6R, NCR3, SIGLEC5, SIGLEC14, and TAPBP) were observed to have cross-cancer effects. Notably, 5 of these identified proteins (CD86, CSF2RA, CXCL10, IL6R, and TAPBP) have been targeted for drug development in cancer therapy; 8 proteins (ADPGK, CD86, CXCL10, GZMM, IL6R, SIGLEC5, SIGLEC14, TAPBP) could be modulated by healthy lifestyles. CONCLUSION: Our study identified 39 circulating protein biomarkers with convincing causal evidence for 7 site-specific cancers, with 11 proteins demonstrating cross-cancer effects, and prioritized the proteins as potential intervention targets by either drugs or lifestyle changes, which provided new insights into the etiology, prevention, and treatment of cancers.

Short- and long-term outcomes of laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making: a high-volume center retrospective study with propensity score matching.

BACKGROUND: Some studies have demonstrated the short-term recovery course for patients who underwent laparoscopic gastrectomy according to preoperative computed tomography angiography (CTA) assessment. However, reports of the long-term oncological outcomes are still limited. METHODS: The data of 988 consecutive patients who underwent laparoscopic or robotic radical gastrectomy between January 2014 and September 2018 were analyzed retrospectively at our center, and propensity score matching was used to eliminate bias. Study cohorts were divided into the CTA group (n = 498) and the non-CTA group (n = 490) depending on whether preoperative CTA was available. The primary and secondary endpoints were the 3-year overall survival (OS) and disease-free survival (DFS) rates and the intraoperative course and short-term outcomes, respectively. RESULTS: 431 patients were included in each group after PSM. Compared with the non-CTA group, the CTA group had more harvested lymph nodes and less operative time, blood loss, intraoperative vascular injury and total cost, especially in the subgroup analysis with BMI ≥ 25 kg/m2 patients. There was no difference in the 3 year OS and DFS between the CTA group and the non-CTA group. When further stratified by BMI < 25 or ≥ 25 kg/m2, the 3-year OS and DFS were significantly higher in the CTA group than in the non-CTA group in terms of BMI ≥ 25 kg/m2. CONCLUSIONS: Laparoscopic or robotic radical gastrectomy based on preoperative perigastric artery CTA surgical decision-making has the possibility of improving short-term outcomes. However, there is no difference in the long-term prognosis, except for a subgroup of patients with BMI ≥ 25 kg/m2.

Buffering effect of the economizer against PCDD/Fs in flue gas from solid waste incineration plants.

The emission of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from solid waste incineration is always a crucial concern for the society. Less attention has been paid to differentiate its formation and migration in the low temperature range of economizer, leading to a fuzzy understanding on the control of PCDD/Fs before flue gas cleaning. This study first reveals the buffering effect against PCDD/Fs in the economizer, which is contrary to the well-known memory effect, and first recognizes the intrinsic mechanism by 36 sets of full-scale experimental data under three typical operating conditions. Results indicated that the buffering effect, which includes interception and releasing, could remove averagely 82.9 % of PCDD/Fs in flue gas and reconcile PCDD/Fs profiles. The interception effect is dominant and in compliance with the condensation law. The low temperature range of economizer is exactly suitable for the condensation of lowly chlorinated congeners, which condense behind highly chlorinated ones. The releasing effect was non-staple but stimulated by the sudden change of operating condition, proving that PCDD/Fs formation rarely exists in the economizer. The buffering effect is mainly controlled by the physical migration of PCDD/Fs among different phases. The condensation of PCDD/Fs leads to their migration from vapor phase to aerosol and solid phases during flue gas cooling in the economizer. There is no need for excessive anxiety about PCDD/Fs formation in the economizer because it rarely exists. Intensifying the condensation process of PCDD/Fs in the economizer can help relieve the pressure of end-of-pipe measures for PCDD/Fs control.

Cross-cancer pleiotropic analysis identifies three novel genetic risk loci for colorectal cancer.

BACKGROUND: To understand the shared genetic basis between colorectal cancer (CRC) and other cancers and identify potential pleiotropic loci for compensating the missing genetic heritability of CRC. METHODS: We conducted a systematic genome-wide pleiotropy scan to appraise associations between cancer-related genetic variants and CRC risk among European populations. Single nucleotide polymorphism (SNP)-set analysis was performed using data from the UK Biobank and the Study of Colorectal Cancer in Scotland (10 039 CRC cases and 30 277 controls) to evaluate the overlapped genetic regions for susceptibility of CRC and other cancers. The variant-level pleiotropic associations between CRC and other cancers were examined by CRC genome-wide association study meta-analysis and the pleiotropic analysis under composite null hypothesis (PLACO) pleiotropy test. Gene-based, co-expression and pathway enrichment analyses were performed to explore potential shared biological pathways. The interaction between novel genetic variants and common environmental factors was further examined for their effects on CRC. RESULTS: Genome-wide pleiotropic analysis identified three novel SNPs (rs2230469, rs9277378 and rs143190905) and three mapped genes (PIP4K2A, HLA-DPB1 and RTEL1) to be associated with CRC. These genetic variants were significant expressions quantitative trait loci in colon tissue, influencing the expression of their mapped genes. Significant interactions of PIP4K2A and HLA-DPB1 with environmental factors, including smoking and alcohol drinking, were observed. All mapped genes and their co-expressed genes were significantly enriched in pathways involved in carcinogenesis. CONCLUSION: Our findings provide an important insight into the shared genetic basis between CRC and other cancers. We revealed several novel CRC susceptibility loci to help understand the genetic architecture of CRC.

Bioinformatic Analysis of PTTG Family and Prognosis and Immune Cell Infiltration in Gastric Cancer.

Gastric cancer is the sixth highest incidence rate in the world. Although treatment has made progress, the prospect of gastric cancer patients is bleak. Difficulties and future prospects of immunotherapy in cancer treatment. Adaptive cell therapy, cancer vaccines, gene therapy, and monoclonal antibody therapy have all been used in gastric cancer with some initial success. PTTGs (pituitary tumor-transforming genes) have been proven to be closely related to the prognosis of many malignant tumors. However, the prognosis and immune cell infiltration of gastric adenocarcinoma (STAD) remain unclear. We retrieved multiple databases to understand the possible activity of PTTGs and their expression in gastric cancer, as well as their relationship with clinical data, overall survival rate, first progression, and survival rate after progression. PTTGs are overexpressed in STAD tumor tissues. Many clinical variables are closely related to PTTGs. In addition, PTTG was associated with overall survival independent of disease. In addition, the expression of PTTG1/2 was positively correlated with the molecular status of the immune checkpoint and negatively correlated with the infiltration of various immune cells. Data research shows that PTTG and STAD are closely related. This paved the way for future research, revealed the complex pathophysiology of gastric cancer, and introduced an effective new treatment.

Bioinformatics analysis: relationship between adrenocortical carcinoma and KIFs.

Adrenal cortical cancer has a relatively low incidence, but a dismal 5-year survival rate. Surgical intervention is the gold standard of care today. In spite of this progress, patients continue to have a dismal outlook. The results of this study demonstrate that kinin superfamily (KIF) has strong ties to many different types of cancers. However, their prognostic and immune cell infiltration of adrenocortical carcinoma (ACC) remain unclear. Multiple databases were searched for information on the transcription level of KIFs, its correlation with clinical data of ACC patients, patients' overall survival (OS), first progression survival (FPS), and progression free interval (PFI). Its role and association with immune cells were also investigated. We observed an increase in the expression of KIF4A, KIF11, KIF20A, and KIF22. There was a strong correlation between them and the advancedness of ACC tumors. Parallel to this, KIFs are connected to the concepts of operating systems, distributed file systems, and partitioned file systems. Similarly, we found five key genes, PRC1, PLK1, KIF23, KIFC1, and KIF5A, through data analysis, all of which participate in multiple cellular pathways. Both KIF4A and KIF11 expression levels were marginally positively correlated with immune infiltration. Because KIF4A, KIF11, KIF20A, and KIF22 are involved in multiple ACC processes and can influence the onset and progression of ACC, they provide a mechanistically grounded framework for diagnosing and managing the disease.

The targets of aspirin in bladder cancer: bioinformatics analysis.

BACKGROUND: The anti-carcinogenic properties of aspirin have been observed in some solid tumors. However, the molecular mechanism of therapeutic effects of aspirin on bladder cancer is still indistinct. We introduced a bioinformatics analysis approach, to explore the targets of aspirin in bladder cancer (BC). METHODS: To find out the potential targets of aspirin in BC, we analyzed direct protein targets (DPTs) of aspirin in Drug Bank 5.0. The protein-protein interaction (PPI) network and signaling pathway of aspirin DPTs were then analyzed subsequently. A detailed analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway has shown that aspirin is linked to BC. We identified overexpressed genes in BC comparing with normal samples by Oncomine and genes that interlinked with aspirin target genes in BC by STRING. RESULTS: Firstly, we explored 16 direct protein targets (DPT) of aspirin. We analyzed the protein-protein interaction (PPI) network and signaling pathways of aspirin DPT. We found that aspirin is closely associated with a variety of cancers, including BC. Then, we classified mutations in 3 aspirin DPTs (CCND1, MYC and TP53) in BC using the cBio Portal database. In addition, we extracted the top 50 overexpressed genes in bladder cancer by Oncomine and predicted the genes associated with the 3 aspirin DPTs (CCND1, MYC and TP53) in BC by STRING. Finally, 5 exact genes were identified as potential therapeutic targets of aspirin in bladder cancer. CONCLUSION: The analysis of relevant databases will improve our mechanistic understanding of the role of aspirin in bladder cancer. This will guide the direction of our next drug-disease interaction studies.

Comparison of clinical profiles and associated factors for acute myocardial infarction among young and very young patients with coronary artery disease.

BACKGROUND: This study aimed to compare the profiles of young and very young patients with coronary artery disease (CAD) and explore the factors associated with acute myocardial infarction (AMI) based on age. METHODS: Young CAD patients aged between 18 and 44 years diagnosed by angiography were enrolled retrospectively. They were divided into two groups according to age: young CAD was defined as patients aged between 36 and 44 years, and very young CAD was defined as patients aged between 18 and 35 years. Demographic and clinical characteristics of the patients were collected. RESULTS: In total, 9286 patients were included in the final database. Most were assigned to the young CAD group (86.5%), and 1250 (13.5%) had very young CAD. Most demographic and clinical characteristics of the young and very young patients with CAD differed significantly. The proportion of patients with CAD in the total population increased with age, whereas the incidence of AMI showed a decreasing trend. A previous percutaneous coronary intervention (PCI) was negatively associated with AMI. Dyslipidemia, current smoking, and hyperhomocysteinemia were positively associated with AMI in the overall and young population with CAD. CONCLUSIONS: The clinical profiles and factors associated with AMI in CAD patients of different ages were significantly different. Lifestyle-related factors were significantly associated with AMI in young patients with CAD.

Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

The Association between Smoking Cessation and Depressive Symptoms: Diet Quality Plays a Mediating Role.

OBJECTIVE: This cross-sectional study aimed to explore the association between smoking cessation and depressive symptoms and investigate the mediating role of dietary quality. METHODS: We used data from the 2007-2014 National Health and Nutrition Examination Survey. Logistic regression models were applied to evaluate the associations between smoking cessation and depressive symptoms. Stratified analysis was performed according to different HEI levels. We examined the mediating role of HEI in the relationship between depressive symptoms and cessation duration using the Karlson-Holm-Breen (KHB) method. RESULTS: A total of 20,004 participants aged 20 years or older were included in the analyses. There were significant correlations between years for smoking cessation and depressive symptoms (OR: 0.985, 95% CI: 0.971~0.999) after adjusting for correlation covariables. A likelihood ratio test showed that there was an interaction between smoking cessation and diet quality (p = 0.047). In the mediation analysis, we estimated that the increase in HEI scores after quitting smoking could explain the 6.91% decline in depressive symptoms. CONCLUSION: In this cross-sectional study, smoking cessation showed a protective effect on depressive symptoms and that diet quality can influence and mediate this association.

Quantitative coronary computed tomography angiography assessment of chronic total occlusion percutaneous coronary intervention.

Background: Morphological and clinical characteristics are widely used to predict the success of percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO). However, the impact of quantitative characteristics derived from coronary computed tomography angiography (CCTA) on guidewire crossing and PCI success is still unclear. This study aimed to explore the association between these quantitative characteristics and the difficulty of PCI for CTO. Methods: A total of 207 CTO lesions from 201 patients (84.6% male; mean age 58.9 years) with pre-procedural CCTA scans who had undergone PCI for CTO were retrospectively enrolled in this case-control study. A semi-automated CCTA plaque-analysis software was adopted to obtain the total plaque volume and volume of each component according to the Hounsfield Unit (HU) value, including dense calcium (>351 HU), fibrous (131-350 HU), fibrofatty (76-130 HU), and necrotic core (-30-75 HU) tissue. Differences in the quantitative characteristics of the CTO lesions were compared between: (I) the group of lesions with successful guidewire crossing (≤30 min) and the group with failed guidewire crossing (≤30 min); (II) the group of lesions with procedural success [defined as achieving residual stenosis of <30% and a grade 3 thrombolysis in myocardial infarction (TIMI) flow] and the group with procedural failure. Logistic regression was used to explore the association of quantitative characteristics with successful guidewire crossing in ≤30 min and procedural success. Results: A total of 131 (63.3%) lesions of 126 patients achieved successful guidewire crossing in ≤30 min and 157 (75.8%) lesions of 152 (75.6%) patients achieved procedural success. Quantitative characteristics such as occlusion length, plaque volume, volume of dense calcium, and fibrous and fibrofatty tissue showed significant differences between the groups of lesions with successful guidewire crossing in ≤30 min and with failed guidewire crossing in ≤30 min, as well as the groups of lesions with procedural success and with procedural failure. According to the results of logistic regression analysis, lower percentages of dense calcium [odds ratio (OR) =0.970, 95% confidence interval (CI): 0.950 to 0.991; P=0.004] and fibrous (OR =0.970, 95% CI: 0.949 to 0.992; P=0.007) tissue and higher percentage of necrotic core tissue (OR =1.018, 95% CI: 1.005 to 1.030; P=0.005) were significantly associated with successful guidewire crossing in ≤30 min. Decreased percentages of dense calcium (OR =0.969; 95% CI: 0.949 to 0.989; P=0.002) and fibrous tissue (OR =0.966, 95% CI: 0.944 to 0.990; P=0.005) and higher percentage of necrotic core tissue (OR =1.022, 95% CI: 1.008 to 1.036; P=0.002) were associated with procedural success. After adjusting for cardiovascular risk factors, the percentages of dense calcium, fibrous, and necrotic core tissue were still associated with successful guidewire crossing in ≤30 min, and the quantitative parameters showed consistent association with procedural success. Conclusions: Quantitative characteristics derived from CCTA for CTO are associated with successful guidewire crossing and procedural success of PCI.

[Prospective randomized controlled trial on the effectiveness of low-dose and high-dose intravenous tranexamic acid in reducing perioperative blood loss in single-level minimally invasive transforaminal lumbar interbody fusion].

Objective: A prospective randomized controlled trial was conducted to study the effectiveness and safety of intravenous different doses tranexamic acid (TXA) in single-level unilateral minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Methods: The patients treated with single-level unilateral MIS-TLIF between September 2019 and October 2020 were enrolled and randomly classified into low-dose TXA (LD) group (n=39), high-dose TXA (HD) group (n=39), and placebo-controlled (PC) group (n=38). The LD, HD, and PC groups received intravenous TXA 20 mg/kg, TXA 50 mg/kg, the same volume of normal saline at 30 minute before skin incision after general anesthesia, respectively. There was no significant difference on baseline characteristics and preoperative laboratory results among 3 groups (P>0.05), including age, gender, body mass index, surgical segments, hematocrit (HCT), hemoglobin (HGB), prothrombin time (PT), international normalized ratio (INR), D-dimer, fibrin degradation products (FDP), activated partial prothromboplastin time (APTT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), urea. The intraoperative blood loss (IBL), postoperative drainage volume, operation time, total blood loss (TBL), hidden blood loss (HBL), blood transfusion, hematological examination indexes on the first day after operation, and the incidence of complications within 1 month were compared among the 3 groups. Results: There were 3, 2, and 4 patients in the LD, HD, and PC groups who underwent autologous blood transfusion, respectively, and there was no allogeneic blood transfusion patients in the 3 groups. There was no significant difference in IBL, postoperative drainage volume, and operation time between groups (P>0.05). The TBL, HBL, and the decreased value of HGB in LD and HD groups were significantly lower than those in PC group (P<0.05), and TBL and HBL in HD group were significantly lower than those in LD group (P<0.05); the decreased value of HGB between LD group and HD group showed no significant difference (P>0.05). On the first day after operation, D-dimer in LD and HD groups were significantly lower than that in PC group (P<0.05); there was no significant difference between LD and HD groups (P>0.05). There was no significant difference in other hematological indexes between groups (P>0.05). All patients were followed up 1 month, and there was no TXA-related complication such as deep venous thrombosis of lower extremity, pulmonary embolism, and epilepsy in the 3 groups. Conclusion: Intravenous administration of TXA in single-level unilateral MIS-TLIF is effective and safe in reducing postoperative TBL and HBL within 1 day in a dose-dependent manner. Also, TXA can reduce postoperative fibrinolysis markers and do not increase the risk of thrombotic events, including deep venous thrombosis and pulmonary embolism.

Uniform platinum nanoparticles loaded on Universitetet i Oslo-66 (UiO-66): Active and stable catalysts for gas toluene combustion.

Highly dispersed Pt nanoparticles supported UiO-66 catalysts were successfully prepared by the incipient wetness impregnation method. Their thermal catalytic performances were evaluated by toluene degradation. The physicochemical properties of the samples were characterized using a series of characterization methods. The catalytic activity of catalysts remained essentially unchanged in the high weight hourly space velocity, stability and water resistance test, which also indicated good catalytic performance. In the reusability test, the catalytic performance was found to be enhanced after the reaction, because of the catalyst might follow a Pt0-PtO synergistic catalytic mechanism (similar to Mars-van Krevelen mechanism) and there was a phase transition between Pt0 and PtO during the reaction. Firstly, the toluene adsorbed on the catalyst surface was oxidized by the activated lattice oxygen of the PtO. Then, consumption of oxygen atoms led to formation of oxygen vacancies, and finally the molecular oxygen adsorbed by Pt0 was activated and passed to the PtO to supplement the oxygen vacancies, forming a redox cycle. In addition, the possible catalytic oxidation mechanism of toluene was also revealed.

Associations and dose-response relationships between different kinds of urine polycyclic aromatic hydrocarbons metabolites and adult lung functions.

Associations and dose-response relationships between different kinds of urine polycyclic aromatic hydrocarbons (PAHs) metabolites and lung functions in general American adults were unknown. Data from the National Health and Nutrition Examination Survey database of the 2009-2012 cycles were used. The independent variables were urine PAHs adjusted for urine creatinine, including 1-hydroxynaphthalene (1-NAP), 2-hydroxynaphthalene (2-NAP), 3-hydroxyfluorene (3-FLU), 2-hydroxyfluorene (2-FLU), 3-hydroxyphenanthrene (3-PHE), 1-hydroxyphenanthrene (1-PHE), 2-hydroxyphenanthrene (2-PHE), 1-hydroxypyrene (1-PYR), and 9-hydroxyfluorene (9-FLU). The dependent variables were lung function indices including the forced vital capacity (FVC), the 1st second of a forceful exhalation (FEV1), the ratio of FEV1/FVC, the forced expiratory flow rate 25-75% (FEF25%-75%), and the fractional exhaled nitric oxide (FENO). Multivariate linear regression analyses and the restricted cubic splines were used. Except for 1-PHE and 9-FLU, FEF25%-75% decreased in quartile (Q) 4 of all the remaining seven PAHs; FEV1 decreased in Q4 of 2-NAP, 3-PHE, 2-PHE, and 9-FLU, with ß (SE) of -121.89 (45.46), -105.21 (33.57), -143.67 (40.60), and -127.71 (37.14), respectively. FVC decreased only in Q3 of 9-FLU, with ß (SE) of -142.24 (56.54); FEV1/FVC decreased in Q4 of all PAHs except for 2-FLU. Besides, FENO decreased in Q4 of all PAHs in smokers, while in non-smokers, the results were opposite. The dose-response relationships were non-linear. In conclusion, we found that urine PAHs may relate to the changes in lung functions. Besides, smoking status had a significant influence on FENO; FENO decreased in smokers while increased in non-smokers, suggesting that PAHs exposure may relate to airway inflammation.

Trends in low-density lipoprotein cholesterol level among Chinese young adults hospitalized with first acute myocardial infarction.

BACKGROUND: Representative data has shown a linear increase in mean low-density lipoprotein cholesterol (LDL-C) levels among Chinese adults, contributing to the burden of atherosclerotic cardiovascular disease (ASCVD). This study aimed to assess the trends in LDL-C levels and their association with coronary artery stenosis during the first acute myocardial infarction (AMI) in young Chinese adults. METHODS: A retrospective study including 2,781 adults, aged 18-44 years, hospitalized for their first AMI in Beijing Anzhen hospital between 2007 and 2017 was performed. RESULTS: Mean LDL-C level was 2.82±0.97 mmol/L with the prevalence of elevated LDL-C being 21.6% (601/2,781). Of the study, only 4.2% were aware of their elevated LDL-C status. Neither mean LDL-C concentration nor prevalence of elevated LDL-C showed a downward trend between 2007 and 2017 (P>0.05). Patients aged <35 years had the highest LDL-C level and frequency of elevated LDL-C among the three age groups (aged <35, 35-39, and 40-44 years; P<0.01). Patients with LDL-C ≥3.4 mmol/L evinced a more than 50% increased risk of coronary artery stenosis compared with those with LDL-C <1.4 mmol/L [adjusted odds ratio (OR) 3.19; 95% confidence interval (CI): 1.62 to 6.29]. Of the study, 62.0% had at least two conventional risk factors (RFs), and smoking, accompanied by hypertension, obesity, or elevated LDL-C were the most common combinations. CONCLUSIONS: The current study provides an overview of trends in LDL-C level and elevated LDL-C among young adults at the time of first AMI. Patients had a high prevalence of elevated LDL-C but low awareness of this status. Coronary artery stenosis was positively correlated with LDL-C level. Preventive strategies, including public education regarding cholesterol levels and benefits of maintaining LDL-C below 3.4 mmol/L should be considered for young adults as a primary preventive strategy.