Targeting Mitochondria-Inflammation Circuit by ß-Hydroxybutyrate Mitigates HFpEF.

RATIONALE: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF. OBJECTIVE: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model. METHODS AND RESULTS: By combining the age, long-term high-fat diet, and desoxycorticosterone pivalate challenge in a mouse model, we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of IL (interleukin)-1ß/IL-18 and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing ß-hydroxybutyrate level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokine-triggered mitochondrial dysfunction and fibrosis. Moreover, ß-hydroxybutyrate downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of CS (citrate synthase) and inhibition of fatty acid uptake. CONCLUSIONS: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, which can be ameliorated by promoting ß-hydroxybutyrate abundance.

Myocardial-Targeting Tannic Cerium Nanocatalyst Attenuates Ischemia/Reperfusion Injury.

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Medications or surgery have been considered as effective protocols to treat IHD for decades. Yet the reperfusion of the blood flow frequently leads to the generation of excessive reactive oxygen species (ROS), causing prominent and irreversible damage to the cardiomyocytes. In the present work, tannic acid-assembled tetravalent cerium (TA-Ce) nanocatalysts with appealing cardiomyocyte-targeting and antioxidation capability have been synthesized and applied for the effective and biocompatible ischemia/reperfusion injury therapeutics. TA-Ce nanocatalysts could effectively rescue the cardiomyocytes from oxidative stress induced by H2 O2 challenge as well as oxygen-glucose deprivation in vitro. In the murine ischemia/reperfusion model, cardiac accumulation and intracellular ROS scavenging could be achieved against the pathology, substantially reducing the myocardial infarct area and recovering heart functionality. This work illuminates the design of nanocatalytic metal complexes and their therapeutic prospects in ischemic heart diseases with high effectiveness and biocompatibility, paving the way for the clinical translation from bench to bedside.

Mitochondrial protein hyperacetylation underpins heart failure with preserved ejection fraction in mice.

Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction (HFrEF). The prevalence of HFpEF continues to increase, while the pathogenic mechanisms underlying HFpEF remain largely elusive and evidence-based therapies are still lacking. This study was designed to investigate the metabolic signature of HFpEF and test the potential therapeutic intervention in a mouse model. By utilizing a "3-Hit" HFpEF mouse model, we observed a global protein hyperacetylation in the HFpEF hearts as compared to the pressure overload-induced HFrEF and adult/aged non-heart failure (NHF) hearts. Acetylome analysis identified that a large proportion of the hyperacetylated proteins (74%) specific to the HFpEF hearts are in mitochondria, and enriched in tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and fatty acid oxidation. Further study showed that the elevated protein acetylation in the HFpEF hearts was correlated with reduced NAD+/NADH ratio, impaired mitochondrial function, and depleted TCA cycle metabolites. Normalization of NAD+/NADH ratio by supplementation of nicotinamide riboside (NR) for 30 days downregulated the acetylation level, improved mitochondrial function and ameliorated HFpEF phenotypes. Therefore, our study identified a distinct protein acetylation pattern in the HFpEF hearts, and proposed NR as a promising agent in lowering acetylation and mitigating HFpEF phenotypes in mice.

An SNP at the target site of cid-miR-nov-1043 in the TOLLIP 3' UTR decreases mortality rate in grass carp subjected to ENU-induced mutagenesis following grass carp reovirus infection.

N-ethyl-N-nitrosourea (ENU) selection is a useful technique to generate new mutations that may cause some functional changes in the gene. Through our previous genomic bulked segregant analysis (BSA), one single nucleotide polymorphism (SNP) at the 3' UTR of Toll interacting protein gene (TOLLIP982T>C) was identified in grass carp (Ctenopharyngodon idella) subjected to ENU-induced mutagenesis. We found that the overexpression of cid-miR-nov-1043 mimics significantly suppressed the luciferase activity of the TOLLIP 3' UTR, but TOLLIP982T>C mutation at the target site can decrease the binding affinity between the miRNA cid-miR-nov-1043 and TOLLIP 3' UTR, reducing the inhibition of TOLLIP mRNA transcription in grass carp subjected to ENU-induced mutagenesis. More importantly, we demonstrated that TOLLIP mRNA transcription levels in the gills, liver, kidney and the isolate white cells of the mutant grass carp were significantly (p < 0.01) higher than those in the corresponding tissues from the wild-type grass carp following infection with Grass Carp Reovirus (GCRV) for seven days, while the downstream gene of TOLLIP transforming growth factor ß-activated kinase 1 (TAK1) and TAK1-binding protein 1 (TAB1), were higher expressed in wild-type grass carp. As a negative regulator in the pro-inflammatory pathway of NF-κB, TOLLIP inhibits the excessive inflammation in ENU grass carp after GCRV infection. Consistent with the TOLLIP expression, histopathological results demonstrated more severe inflammation in wild-type grass carp, compared to the TOLLIP982T>C mutant grass carp on the seventh day. Severe inflammation will lead to thoroughly infiltration of chloride and inflammatory cells in the gill filaments. This seriously hindered the exchange of oxygen, which ultimately disrupted blood circulation. Meanwhile, the survival rate of the mutant grass carp was significantly (p < 0.01) higher than that of the wild-type grass carp, indicating that the TOLLIP982T>C mutants showed strong anti-viral abilities. Our results revealed that an SNP in the TOLLIP 3' UTR may contribute to the suppression of serve inflammation subjected to ENU-induced mutagenesis following GCRV infection, which may be helpful for future resistant breeding development of grass carp.

Nanozymes-recent development and biomedical applications.

Nanozyme is a series of nanomaterials with enzyme-mimetic activities that can proceed with the catalytic reactions of natural enzymes. In the field of biomedicine, nanozymes are capturing tremendous attention due to their high stability and low cost. Enzyme-mimetic activities of nanozymes can be regulated by multiple factors, such as the chemical state of metal ion, pH, hydrogen peroxide (H2O2), and glutathione (GSH) level, presenting great promise for biomedical applications. Over the past decade, multi-functional nanozymes have been developed for various biomedical applications. To promote the understandings of nanozymes and the development of novel and multifunctional nanozymes, we herein provide a comprehensive review of the nanozymes and their applications in the biomedical field. Nanozymes with versatile enzyme-like properties are briefly overviewed, and their mechanism and application are discussed to provide understandings for future research. Finally, underlying challenges and prospects of nanozymes in the biomedical frontier are discussed in this review.

Erector spinae plane block for postoperative analgesia in spine surgery: a systematic review and meta-analysis.

PURPOSE: Although in recent years some randomized controlled trails (RCTs) have explored the analgesic effect of erector spinae plane block (ESPB) in spine surgery, their results are controversial. Our study aimed to examine the analgesic effect of preoperative ESPB in spine surgery by a meta-analysis of RCTs. METHODS: The articles of RCTs that compared preoperative ESPB with no block in terms of the analgesic effect in adult patients following spine surgery were eligible for inclusion. The primary outcome was the pain scores reported by Visual Analog Scale or Numerical Rating Scale of pain at different time intervals in 48 h after surgery. The secondary outcomes included postoperative opioid consumption, rescue analgesia requirement, opioid-related side effects and complications associated with ESPB. RESULTS: Twelve studies involving 828 patients were eligible for our study. Compared with no block, ESPB had a significant effect on reducing postoperative pain scores at rest and at movement at different time intervals except at movement at 48 h. ESPB significantly decreased opioid consumption in 24 h after surgery (SMD - 1.834; 95%CI - 2.752, - 0.915; p < 0.001; I2 = 89.0%), and reduced the incidence of rescue analgesia (RR 0.333; 95%CI 0.261, 0.425; p < 0.001; I2 = 0%) and postoperative nausea and vomiting (RR 0.380; 95%CI 0.272, 0.530; p < 0.001; I2 = 9.0%). Complications associated with ESPB were not reported in the included studies. CONCLUSION: Our meta-analysis demonstrates that ESPB is effective in decreasing postoperative pain intensity and postoperative opioid consumption in spine surgery. Therefore, for the management of postoperative pain following spine surgery, preoperative ESPB is a good choice.

Adductor canal block is similar to femoral nerve block for the quality of rehabilitation after arthroscopic partial meniscectomy.

PURPOSE: Adductor canal block (ACB) provides postoperative pain relief as effectively as femoral nerve block (FNB) does, and it preserves the strength of the quadriceps femoris. However, its effect on rehabilitation after arthroscopic partial meniscectomy has not been reported. The purpose of this study was to determine the effect of pre-operative ACB and FNB on the quality of rehabilitation after arthroscopic partial meniscectomy. METHODS: A total of 150 patients undergoing arthroscopic partial meniscectomy were randomly allocated to the FNB group (receiving 0.3% ropivacaine 30 ml at the thighroot-femoral nerve), the ACB group (receiving 0.3% ropivacaine 30 ml at mid-thigh adductor canal), or the control group. The primary outcome was the Hospital for Special Surgery (HSS) knee score on the 30th postoperative day. RESULTS: The HSS knee score of the ACB group on the 30th day after the operation was significantly higher than those of the FNB and control groups (88.6 ± 5.3 vs. 85.3 ± 6.9 and 81.2 ± 5.9, respectively; P < 0.05). Both the ACB and FNB groups showed excellent rehabilitation, indicating similar rehabilitation quality for both treatments. CONCLUSION: ACB is similar to FNB concerning the quality of rehabilitation and pain relief after arthroscopic partial meniscectomy, while ACB has little effect on the strength of the quadriceps femoris. LEVEL OF EVIDENCE: I TRIAL REGISTRATAION: This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INC-16008346).

Entrapment of a laryngotracheal topical anesthesia kit during tracheobronchial foreign body removal: a case report.

BACKGROUND: In order to reduce the irritation of the airway during tracheobronchial foreign body (TFB) removal, tracheal surface anesthesia is usually performed using a laryngotracheal topical anesthesia (LTA) kit (LTA20, Highgreen Medical Technology Company, China), but difficulty in withdrawing the LTA kit is rarely reported. We present a case of a difficulty to withdraw the LTA kit due to its entrapment by the movement of a TFB. CASE PRESENTATION: A 1-year-old girl was undergoing TFB removal. After the surgeon completed the tracheal surface anesthesia, the girl suddenly suffered from bucking, leading to the dislodgment of the TFB to the subglottic region, complicating the withdrawal of the LTA applicator. At the same time, the girl's oxygen saturation (SpO2) decreased to 91% and her heart rate dropped from 150 to 100 bpm. Atropine and succinylcholine were administered intravenously immediately, then the surgeon tried to free the TFB by pushing it back into the trachea, after which the LTA applicator was easily withdrawn, and TFB was removed successfully. The girl was discharged from hospital without any complications 2 days later. CONCLUSION: This case report draws our attention to a significant anesthetic clinical consideration during the application of topical anesthesia on the trachea for TFB removal. The possibility of coughing or bucking can lead to migration of the TFB with subsequent airway obstruction, so the depth of anesthesia must be sufficient to prevent harmful reflexes. Also, strong teamwork and good communication are paramount to avoid serious complications.

rs10719 Polymorphism Located within DROSHA 3'-Untranslated Region is Responsible for Development of Primary Hypertension by Disrupting Binding with microRNA-27b.

BACKGROUND MiR-27b is reportedly involved with many diseases (e.g., gastric cancer) by acting on different signaling pathways. In this study, we aimed at understanding the relationship between miR-27b and hypertension and its underlying molecular mechanism. MATERIAL AND METHODS Peripheral blood was collected from patients with hypertension, and statistical analysis was performed to study the association between rs10719 and risk of hypertension. Tissue samples were collected from patients with lung cancer, and the expression of miR-27b and DROSHA was determined using Western blot analysis and real-time PCR. RESULTS We first searched the miRNA database online, and identified DROSHA as a virtual target of miR-27b with the "seed sequence" located within the 3'-UTR of the target gene, and then validated DROSHA to be the direct gene via luciferase reporter assay system. We also established the negative regulatory relationship between miR-27b and DROSHA via studying the relative luciferase activity. We also conducted real-time PCR to study the mRNA and protein expression level of miR-27b among different groups. Furthermore, we conducted real-time PCR and densitometry analysis to study the mRNA and protein expression level of DROSHA among different groups of cells treated with scramble control, miR-27b mimics, DROSHA siRNA, and miR-27b inhibitors to verify the negative regulatory relationship between MiR-27b and DROSHA. CONCLUSIONS The presence of rs10719 disrupted the interaction between miR-27b and DROSHA, which might be the underlying mechanism of the observation that rs10719 is significantly associated with risk of primary hypertension.

Dr.VIS v2.0: an updated database of human disease-related viral integration sites in the era of high-throughput deep sequencing.

Dr.VIS is a database of human disease-related viral integration sites (VIS). The number of VIS has grown rapidly since Dr.VIS was first released in 2011, and there is growing recognition of the important role that viral integration plays in the development of malignancies. The updated database version, Dr.VIS v2.0 (http://www.bioinfo.org/drvis or bminfor.tongji.edu.cn/drvis_v2), represents 25 diseases, covers 3340 integration sites of eight oncogenic viruses in human chromosomes and provides more accurate information about VIS from high-throughput deep sequencing results obtained mainly after 2012. Data of VISes for three newly identified oncogenic viruses for 14 related diseases have been added to this 2015 update, which has a 5-fold increase of VISes compared to Dr.VIS v1.0. Dr.VIS v2.0 has 2244 precise integration sites, 867 integration regions and 551 junction sequences. A total of 2295 integration sites are located near 1730 involved genes. Of the VISes, 1153 are detected in the exons or introns of genes, with 294 located up to 5 kb and a further 112 located up to 10 kb away. As viral integration may alter chromosome stability and gene expression levels, characterizing VISes will contribute toward the discovery of novel oncogenes, tumor suppressor genes and tumor-associated pathways.

[Role of p38 mitogen activated protein kinase signaling pathway in lung ischemia-reperfusion protection offered by HOE642].

OBJECTIVE: To explore the protective effect of sodium channels antagonists HOE642 on lung ischemia reperfusion and the role of the p38 mitogen activated protein kinase (p38MAPK) signaling pathway in this process.
 Methods: A total of 36 mice were randomly divided into a sham operation group (SHAM group), a lung ischemia reperfusion group (I/R group) and a lung ischemia reperfusion+HOE642 group (HOE group). The water content was detected by electronic scales, and the lung tissue pathological changes were observed under optical microscope. The inflammatory cytokines including IL-6 and TNF-α were examined by ELISA. The intracellular calcium fluorescence intensity was examined and observed under fluorescence microscope, and the protein expression of p38MAPK was detected by Western blot.
 Results: Lung water content in the HOE group was lower than that in the I/R group, but higher than that in the SHAM group (both P<0.05). Lung interstitial edema, hemorrhage, lung tissue inflammatory cells infiltration were significantly alleviated in the HOE group than those in the I/R group, while the injury in the HOE group was aggravated than those in the SHAM group (both P<0.05). The IL-6 and TNF-α in lung tissues in the HOE group were lower than those in the I/R group, but higher than those in the SHAM group (both P<0.05). Intracellular calcium fluorescence intensity in the HOE group was lower than that in the I/R group, but higher than that in the SHAM group (both P<0.05). The protein expression of p38MAPK in lung tissues in the HOE group was lower than that in the I/R group, but higher than that in the SHAM group (both P<0.05).
 Conclusion: HOE642 may exert protective effect on pulmonary I/R injury through regulation of the p38MAPK signaling pathway, resulting in reduction of intracellular calcium ion concentration and calcium overload, and decrease of inflammatory response.

Is new American Thyroid Association risk classification for hereditary medullary thyroid carcinoma applicable to Chinese patients? A single-center study.

OBJECTIVE: The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy. METHODS: A total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. RESULTS: In univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040-1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607-38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism. CONCLUSIONS: In Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.

[Analysis of effect of screening of esophageal cancer in 12 cities and counties of Henan province].

OBJECTIVE: To evaluate effect of screening of esophageal cancer at rural areas in Henan province. METHODS: At rural areas with high incidence of upper gastrointestinal carcinoma in Henan province total of 88,263 persons with 40 to 69 years old were set to the target population of the screening by the 12 cities and countries and endoscope and pathology diagnosis were performed during 2009-2013. For patients with precancerous lesions, follow-up visits were conducted and defined as follows: once in three years for patients with mild dysplasia, once per year for moderate hyperplasia patients, the patients with severe intraepithelial neoplasia/carcinoma in situ should be treat, at least once per year for those one who didn't under treatment. The result data of screening were summarized and detection rates of esophagus hyperplasia, carcinoma in situ, early and middle-late cancer were calculated, as well as the early diagnosis rate. The result between first round and follow-up screening was compared. RESULTS: Target population were examined in first round screening. There were 8,434 persons with above mild dysplasia and the detection rate was 9.56%, among them there were 7,224 (8.18%) cases with light-middle hyperplasia, 789 (0.89%) cases with serious dysplasia or cancer in situ, 239 (0.27%) cases with early cancer and 182 (0.21%) cases with middle-late cancer. The sum of serious dysplasia or cancer in situ and early cancer was 1 028 and the early detection rate was 84.96% (1,028/1,210). From 2012 to 2013, the follow-up screening for persons with light-middle hyperplasia which should be followed 4,230 cases, there were 2 853 people to take in screening and compliance was 67.45%. Total of 94 cases were diagnosed with cancer in situ or early cancer. The detection rate and the early detection rate were 3.29% and 100%, respectively. The rates of detection and early detection in phase of follow-up screening were statistically significantly higher than that in first round screening respectively (P<0.001). CONCLUSION: At rural areas of high incidence upper gastrointestinal carcinoma in Henan province, the screening with endoscope had good effect and strengthening the follow-up screening could increase the effect.

[Analysis of results of endoscopic screening of esophageal, gastric cardia and gastric cancers in high risk population].

OBJECTIVE: To summarize the results of endoscopic screening of esophageal, gastric cardiac and gastric cancers in the high-risk population, and analyze the influencing factors such as age, gender and biopsy rate on their detection and early diagnosis rates. METHODS: Nine high incidence cities and counties of esophageal cancer in Henan province were included in this study. People aged 40-69 years were set to the target population. Excluding contraindications for gastroscopy, in accordance with the national technical scheme of early cancer diagnosis and treatment, gastroscopic screening and biopsy pathology for human esophageal, cardiac and gastric cancers were carried out. RESULTS: During the 3-year period, a total of 40 156 subjects were screened. Among them, 18 459 cases of various precancerous lesions (46.0%) were detected. The cancer detection rate was 2.3% (916 cases), including 763 cases of early cancers. The diagnosis rate of early cancers was 83.3%. Precancerous lesions were detected in 9297 cases (23.2%) for esophagus and 9162 cases (22.8%) for gastric cardia as well as stomach, respectively. CONCLUSIONS: The results of this study demonstrate that endoscopic screening is feasible for early detection, diagnosis and treatment of esophageal, gastric cardia and gastric cancers among high risk population in high incidence area. Exploration analysis of relevant affecting factors may help to further improve the screening project for early diagnosis and treatment of those cancers.

Colloidal Phenol-Amine Coating on Implants for Improved Anti-Inflammation and Osteogenesis.

Phenol-amine coatings have attracted significant attention in recent years owing to their adjustable composition and multifaceted biological functionalities. The current preparation of phenol-amine coatings, however, involves a chemical reaction within the solution or interface, resulting in lengthy preparation times and necessitating specific reaction conditions, such as alkaline environments and oxygen presence. The facile, rapid, and eco-friendly preparation of phenol-amine coatings under mild conditions continues to pose a challenge. In this study, we use a macromolecular phenol-amine, Tanfloc, to form a stable colloid under neutral conditions, which was then rapidly adsorbed on the titanium surface by electrostatic action and then spread and fused to form a continuous coating within several minutes. This nonchemical preparation process was rapid, mild, and free of chemical additives. The in vitro and in vivo results showed that the Tanfloc colloid fusion coating inhibited destructive inflammation, promoted osteogenesis, and enhanced osteointegration. These remarkable advantages of the colloidal phenol-amine fusion coating highlight the suitability of its future application in clinical practice.

The Relationship Between Major Food Sources of Fructose and Cardiovascular Outcomes: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

There is emerging evidence of associations between intake of sugar-sweetened beverages (SSBs), those that include various forms of added sugar, and increased risk of cardiovascular disease (CVD) but whether consumption of other dietary sources of fructose affects CVD is unclear. In this study, we conducted a meta-analysis to examine potential dose-response relationships between such foods and CVD, coronary heart disease (CHD), and stroke morbidity and mortality. We systematically searched the literature indexed in PubMed, Embase, and the Cochrane Library from the inception of each database to February 10, 2022. We included prospective cohort studies analyzing the association between at least 1 dietary source of fructose and CVD, CHD, and stroke. Based on data from 64 included studies, summary HRs and 95% CIs were calculated for the highest intake category compared with the lowest, and dose-response analyses were performed. Of all fructose sources examined, only SSB intakes showed positive associations with CVD, giving summary HRs per 250 mL/d increase of 1.10 (95% CI: 1.02, 1.17) for CVD, 1.11 (95% CI: 1.05, 1.17) for CHD, 1.08 (95% CI: 1.02, 1.13) for stroke morbidity, and 1.06 (95% CI: 1.02, 1.10) for CVD mortality. Conversely, 3 dietary sources showed protective associations: between fruits and CVD morbidity (HR: 0.97; 95% CI: 0.96, 0.98), fruits and CVD mortality (HR: 0.94; 95% CI: 0.92, 0.97), yogurt and CVD mortality (HR: 0.96; 95% CI: 0.93, 0.99), and breakfast cereals and CVD mortality (HR: 0.80; 95% CI: 0.70, 0.90). All these relationships were linear except for fruit, which was J-shaped: CVD morbidity was the lowest at 200 g/d and there was no protective association above 400 g/d. These findings indicate that the adverse associations between SSBs and CVD, CHD, and stroke morbidity and mortality do not extend to other dietary sources of fructose. The food matrix seemed to modify the association between fructose and cardiovascular outcomes.

Disutilities Associated with Intravenous Iron Infusions: Results from a Time Trade-off Survey and Diminishing Marginal Utility Model for Treatment Attributes in China.

Purpose: Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions. Methods: An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model. Results: The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15-30 minutes or 30-60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values <0.01). Conclusion: This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients' quality of life.

Grouting anchor cable active advanced support technology for mining roadways.

Because of the deficiencies in safety and economy of the single hydraulic prop passive advanced support, the grouting anchor cable active advanced support technology is proposed with the Changping Coal Mine 53,081 roadway as the engineering background. By using a combination of theoretical analysis, laboratory tests, numerical simulation, and field tests, the influence of different grouting parameters on the diffusion law of grout is studied. Considering the effect of the stress field on grout migration, a grout seepage-stress coupling model is established. Grouting material ratio tests are carried out and grout parameters are tested. The grouting part of the advanced grouting anchor cable is modeled and solved using the COMSOL Multiphysics numerical software. The results show that the grouting material selected is Portland cement 42.5 and water glass double liquid grout, with a slurry ratio of 15% ACZ-1 type additive and 4% water glass content, and a water-cement ratio of 0.6. The grouting pressure for the 53,081 roadway grouting anchor cable advanced support is 5 MPa, the grouting time is 6 min, and the grouting anchor cable spacing is 2000 mm × 1000 mm. The engineering application shows that the maximum roof subsidence is 180 mm, the maximum separation value at a depth of 9 m is 24 mm, and the maximum separation value at a depth of 3 m is 90 mm. The research results have achieved effective advanced support for the 53,081 roadway, replacing the single hydraulic prop, and provided a theoretical basis for the subsequent design of advanced support parameters for mining roadways.

Occurrence and distribution of microplastics in coastal plain soils under three land-use types.

Microplastic pollution is an issue of major environmental concern worldwide. Land-use type may affect the abundance, polymer types, and distribution characteristics of soil microplastics but their distribution remains unknown on the coastal plain of east China. Here, the abundance of microplastics in farmland (FL), plantation (P), and orchard/secondary forest (OSF) soils was determined on the east China coastal plain, and characteristics of the microplastics (shape, size, colour, and polymer composition) were analysed in soil samples collected from 33 sites. The average abundances of microplastics in FL, P, and OSF soils on the coastal plain of the east China coast were 185, 109, and 150 items kg-1, respectively. Small particles, fibres and transparent particles were the main characteristics of the microplastics observed. The polymer types were mainly PP and PET. The abundance of microplastics in farmland was positively correlated with population density in the study area. Therefore, agricultural activities associated with high population density are the main factors leading to the high abundance of microplastics in farmland soil.