Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

Hemin with Peroxidase Activity Can Inhibit the Oxidative Damage Induced by Ultraviolet A.

Excessive reactive oxygen species (ROS), a highly reactive substance that contains oxygen, induced by ultraviolet A (UVA) cause oxidative damage to skin. We confirmed that hemin can catalyze the reaction of tyrosine (Tyr) and hydrogen peroxide (H2O2). Catalysis was found to effectively reduce or eliminate oxidative damage to cells induced by H2O2 or UVA. The scavenging effects of hemin for other free-radical ROS were also evaluated through pyrogallol autoxidation, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)-scavenging assays, and phenanthroline-Fe2+ assays. The results show that a mixture of hemin and tyrosine exhibits strong scavenging activities for H2O2, superoxide anion (O2-·), DPPH·, and the hydroxyl radical (·OH). Furthermore, the inhibition of oxidative damage to human skin keratinocyte (HaCaT) cells induced by H2O2 or UVA was evaluated. The results show that catalysis can significantly reduce the ratio of cell apoptosis and death and inhibit the release of lactate dehydrogenase (LDH), as well as accumulation of malondialdehyde (MDA). Furthermore, the resistance to apoptosis was found to be enhanced. These results show that the mixture of hemin and tyrosine has a significantly protective effect against oxidative damage to HaCaT cells caused by UVA, suggesting it as a protective agent for combating UVA damage.

D-Limonene inhibits the occurrence and progression of LUAD through suppressing lipid droplet accumulation induced by PM2.5 exposure in vivo and in vitro.

BACKGROUND: PM2.5 exposure is associated with lung adenocarcinoma (LUAD), but the mechanism is unclear. The lack of understanding impedes our effort on prevention. This study examined a possible mechanism of lung cancer caused by PM2.5 exposure, and aimed to find a potential intervention for people living in PM2.5 polluted regions. METHODS: Electron microscopy and oil-red staining were conducted to examine the lipid droplet accumulation. Masson's trichrome staining, colony forming, scratch assay and transwell experiment were conducted to evaluate the effect of PM2.5 exposure and D-limonene intervention on the occurrence and progression of LUAD. Potential intervention targets were found by RNA-Seq and verified by luciferase reporter assay. MiR-195 KO mice constructed with CRISPR/Cas9 technology were used to investigate the pivotal role of D-limonene-miR-195-SREBP1/FASN axis. Cohort analysis of lung cancer patients, human LUAD tissues staining and human intervention trial were also conducted to validate the results of cell and animal experiments. RESULTS: Our results showed that PM2.5 exposure induced accumulation of lipid droplets in LUAD cells which accompanied by increased malignant cellular behaviors. PM2.5 exposure led to cleaved N-SREBP1 translocation into nucleus, which activated the de novo lipogenesis pathway. Same changes were also observed in normal lung epithelial cells and normal lung tissue, and mice developed pulmonary fibrosis after long-term exposure to PM2.5. Furthermore, in a cohort of 11,712 lung cancer patients, significant lipid metabolism disorders were observed in higher PM2.5 polluted areas. In view of that, D-limonene was found to inhibit the changes in lipid metabolism through upregulating the expression of miR-195, which inhibited the expression of lipogenic genes (SREBF1/FASN/ACACA) specifically. And a small human intervention trial showed that serum miR-195 was upregulated after oral intake of D-limonene. CONCLUSION: Our findings reveal a new mechanism of pulmonary fibrosis and LUAD that is related to PM2.5 exposure-induced lipid droplet accumulation. We also demonstrate that D-limonene-miR-195-SREBP1/FASN axis is a potential preventive intervention for mediating the progression and development of LUAD induced by PM2.5 exposure. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030200. Registered 25 February 2020, http://www.chictr.org.cn/showproj.aspx?proj=48013.

Efficacy and safety of sequential combination therapy for pulmonary arterial hypertension: A meta-analysis of Randomized-Controlled Trials.

BACKGROUND: Previous meta-analyses of pulmonary arterial hypertension (PAH) combination therapy pooled sequential and initial combination together, which might threaten their authenticity and clinical significance for the difference between two strategies. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) that compared sequential combination therapy (SCT) with background therapy (BT) in PAH patients. Raw data were extracted to calculate risk ratio (RR) or weighted mean difference (WMD) for predefined efficacy and safety outcomes. Mantel-Haenszel fixed or random effects model was used based on heterogeneity. RESULTS: 17 RCTs involving 4343 patients (97.2% of patients with WHO-FC II-III) were included. SCT decreased clinical worsening (RR 0.66, 95% CI 0.58 to 0.76), nonfatal clinical worsening (RR 0.61, 95% CI 0.52 to 0.71), functional class (decrease of 28% in the portion of patients with WHO-FC worsening and increase of 33% in the portion of patients with WHO-FC improvement), and increased 6-min walk distance (WMD 17.68 m, 95% CI 10.16 to 25.20), but didn't reduce mortality, lung transplantation, admission to hospital, and treatment escalation compared with BT. Although any adverse event and serious adverse event were similar between SCT and BT, SCT increased all-cause treatment discontinuation (RR 1.49, 95% CI 1.30 to 1.71) and drug-related treatment discontinuation (RR 2.30, 95% CI 1.86 to 2.84) with higher incidence of headache, flushing, nausea, diarrhoea and jaw pain. CONCLUSIONS: For WHO-FC II-III PAH patients who have established BT, our study reinforced the recommendation of SCT to improve clinical worsening, functional status, and exercise capacity, although with higher incidence of side-effects and withdrawal.

Dapagliflozin, sildenafil and their combination in monocrotaline-induced pulmonary arterial hypertension.

BACKGROUND: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), can reduce cardiovascular events and mortality in patients with heart failure. A number of mechanisms have been proposed to explain the beneficial effects of SGLT2 inhibitors. The purpose of this study was to determine whether dapagliflozin can improve pulmonary vascular remodelling and the efficacy of dapagliflozin as an add-on therapy to sildenafil in rats with pulmonary arterial hypertension (PAH). METHODS: A monocrotaline (MCT)-induced PAH rat model was used in our study. MCT-injected rats were randomly divided into four groups and treated for 3 weeks with daily per os treatment with vehicle, dapagliflozin (1 mg/kg/day), sildenafil (25 mg/kg/day), or a combination of dapagliflozin (1 mg/kg/day) and sildenafil (25 mg/kg/day). Haemodynamic measurements, histological analysis, enzyme-linked immunosorbent assay and western blotting analysis were employed to detect the changes in PAH rats after treatments. RESULTS: Dapagliflozin significantly attenuated MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) in PAH rats. Dapagliflozin effectively decreased the thickening of pulmonary artery media and decreased the muscularization of pulmonary arterioles in PAH rats. Moreover, dapagliflozin attenuated nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation in lung tissues and the levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in plasma. However, dapagliflozin as an add-on therapy to sildenafil in rats with PAH did not show a more pronounced beneficial effect on right ventricular systolic pressure and pulmonary vascular remodelling in MCT rats than sildenafil alone. CONCLUSIONS: Dapagliflozin reduces right ventricular systolic pressure and pulmonary vascular remodelling in a rat model of PAH. However, combination therapy with dapagliflozin and sildenafil was not more effective than monotherapy with sildenafil in PAH rats.

Expression of ApoA5 and its function in the right ventricular failing and remodeling secondary to pulmonary hypertension.

Right heart failure and right ventricular (RV) remodeling were the main reason for mortality of pulmonary hypertension (PH) patients. Apolipoprotein AV (ApoA5) is a key regulator of plasma triglyceride and have multifunction in several target organs. We detected decreased ApoA5 in serum of patients with PH and both in serum and RV of monocrotaline-induced PH model. Exogenously, overexpression ApoA5 by adenovirus showed protective effects on RV failure and RV fibrosis secondary to PH. In addition, in vitro experiments showed ApoA5 attenuated the activation of fibroblast induced by transforming growth factor ß1 and synthesis and secretion of extracellular matrix by inhibiting focal adhesion kinase-c-Jun N-terminal kinase-Smad3 pathway. Finally, we suggest that ApoA5 may potentially be a pivotal target for RV failure and fibrosis secondary of PH.

Elevated plasma Pim-1 and its clinical significance in patients with pulmonary arterial hypertension.

This study was aimed to determine plasma Pim-1 levels in patients with pulmonary arterial hypertension (PAH) and to estimate the clinical value of Pim-1 as a biomarker of PAH. This was a single-centre retrospective study in 111 patients with congenital heart disease (CHD) and idiopathic PAH (IPAH). Those CHD patients were divided into two groups: PAH associated with CHD (PAH-CHD) and CHD without PAH (nPAH-CHD). Plasma Pim-1 levels were measured by enzyme-linked immunosorbent assay. (a) Plasma Pim-1 levels were significantly increased in patients with PAH-CHD and IPAH compared with the healthy control group (27.81 ± 11.34 ng/mL vs 13.02 ± 5.30 ng/mL; 32.81 ± 12.28 ng/mL vs 13.02 ± 5.30 ng/mL, P < 0.05) and nPAH-CHD (27.81 ± 11.34 ng/mL vs 17.33 ± 7.99 ng/mL; 32.81 ± 12.28 ng/mL vs 17.33 ± 7.99 ng/mL, P < 0.05). Pim-1 levels were substantially increased in patients with severe PAH-CHD compared with mild-to-moderate PAH-CHD (19.12 ± 6.70 ng/mL vs 8.54 ± 3.71 ng/mL, P < 0.05). (b) Pim-1 levels were correlated positively with the mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) (r = 0.582, 0.516; P < 0.001, respectively), while negatively with tricuspid annular plane systolic excursion (TAPSE), tricuspid annular plane systolic velocity (S') and right ventricular fractional area changes (RVFAC) (r = -0.375, -0.354, -0.507; P < 0.05, respectively). (c) PAH-CHD and severe PAH-CHD was identified by plasma Pim-1 with a cutoff value of 16.8 ng/mL (P < 0.001) with a sensitivity of 87.3% and a specificity of 65%, and a cutoff value of 20.53 ng/mL (P < 0.001) with a sensitivity of 87.3% and a specificity of 52%, respectively. Plasma Pim-1 levels were significantly higher in patients with PAH-CHD and IPAH. Plasma Pim-1 may represent an effectively biomarker in patients with PAH.

[End-stage renal disease and pulmonary hypertension].

Pulmonary hypertension (PH) is a common complication in patients with end-stage renal disease (ESRD), especially in patients with hemodialysis (HD). Poor prognosis can eventually lead to right heart failure and even death. PH is an independent risk factor for increased mortality in ESRD patients. We should pay attention to these patients in clinic for early detection, prevention and treatment. The pathogenesis of PH in ESRD patients is still unclear so far, which might be related to the increase of pulmonary vascular resistance, pulmonary blood flow, and pulmonary arterial wedge pressure. In addition, the presence of risk factors can promote the development of PH, such as chronic hypoxia, vascular calcification, and inflammation.

Nav1.7 is phosphorylated by Fyn tyrosine kinase which modulates channel expression and gating in a cell type-dependent manner.

Voltage-gated sodium channel Nav1.7 is a key molecule in nociception, and its dysfunction has been associated with various pain disorders. Here, we investigated the regulation of Nav1.7 biophysical properties by Fyn, an Src family tyrosine kinase. Nav1.7 was coexpressed with either constitutively active (FynCA) or dominant negative (FynDN) variants of Fyn kinase. FynCA elevated protein expression and tyrosine phosphorylation of Nav1.7 channels. Site-directed mutagenesis analysis identified two tyrosine residues (Y1470 and Y1471) located within the Nav1.7 DIII-DIV linker (L3) as phosphorylation sites of Fyn. Whole-cell recordings revealed that FynCA evoked larger changes in Nav1.7 biophysical properties when expressed in ND7/23 cells than in Human Embryonic Kidney (HEK) 293 cells, suggesting a cell type-specific modulation of Nav1.7 by Fyn kinase. In HEK 293 cells, substitution of both tyrosine residues with phenylalanine dramatically reduced current amplitude of mutant channels, which was partially rescued by expressing mutant channels in ND7/23 cells. Phenylalanine substitution showed little effect on FynCA-induced changes in Nav1.7 activation and inactivation, suggesting additional modifications in the channel or modulation by interaction with extrinsic factor(s). Our study demonstrates that Nav1.7 is a substrate for Fyn kinase, and the effect of the channel phosphorylation depends on the cell background. Fyn-mediated modulation of Nav1.7 may regulate DRG neuron excitability and contribute to pain perception. Whether this interaction could serve as a target for developing new pain therapeutics requires future study.

[Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis: A case report and literature review].

Pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) is a rare form of pulmonary vascular disease that causes pulmonary arterial hypertension. The diagnosis of PVOD/PCH can be established by the combination of clinical features, physical examination, radiological findings, lung function, bronchoscopy and other resources. There is no established medical therapy for PVOD/PCH, and the only curative therapy for PVOD/PCH is lung transplantation. A girl with PVOD/PCH was diagnosed in the Second Xiangya Hospital. Combining the characteristics for this case with the relevant literature, we summarized the epidemiology, etiology, diagnosis and treatment for the disease to raise doctors' awareness for this rare disease.

Unique expression patterns of multiple key genes associated with the evolution of mammalian flight.

Bats are the only mammals capable of true flight. Critical adaptations for flight include a pair of dramatically elongated hands with broad wing membranes. To study the molecular mechanisms of bat wing evolution, we perform genomewide mRNA sequencing and in situ hybridization for embryonic bat limbs. We identify seven key genes that display unique expression patterns in embryonic bat wings and feet, compared with mouse fore- and hindlimbs. The expression of all 5'HoxD genes (Hoxd9-13) and Tbx3, six known crucial transcription factors for limb and digit development, is extremely high and prolonged in the elongating wing area. The expression of Fam5c, a tumour suppressor, in bat limbs is bat-specific and significantly high in all short digit regions (the thumb and foot digits). These results suggest multiple genetic changes occurred independently during the evolution of bat wings to elongate the hand digits, promote membrane growth and keep other digits short. Our findings also indicate that the evolution of limb morphology depends on the complex integration of multiple gene regulatory networks and biological processes that control digit formation and identity, chondrogenesis, and interdigital regression or retention.

OB-RL silencing inhibits the thermoregulatory ability of Great Roundleaf Bats (Hipposideros armiger).

Previous studies have shown that the hormone Leptin has an important role in mammalian heterothermy by regulating metabolism and food intake via lipolysis, as well as adaptive evolution of Leptin in heterothermic bats driven by selected pressure. However, the mechanism of Leptin in heterothermic regulation in mammals is unknown. By combining previous results, we speculated that the Leptin signaling pathway mediated by OB-RL (Leptin receptor long form) in the hypothalamus is important. OB-RL is one of the products of db gene and mainly distributed in the hypothalamus. In this study, we used OB-RL as a molecular marker, combining with the RNA interference technology and physiological/molecular analyses with Hipposideros armiger (a hibernating bat species) as an animal model, to explore the mechanism of Leptin in heterothermic regulation. Our data showed that all of four anti-OB-RL shRNA lentivirus significantly inhibited OB-RL expression (>90%), and the interference efficiency of PSC1742 lentivirus reached the highest value. In situ hybridization proved that PSC1742 lentivirus significantly decreased the OB-RL expression in the hypothalamus, especially in the ventromedial hypothalamic nucleus (VHM, 86.6%). Physiological analysis demonstrated that the thermoregulatory ability of bats (e.g., reducing core body temperature and heart rate) was significantly depressed after OB-RL silencing in the hypothalamus, and animals could not enter torpor state. Our study for the first time proved that the knock-down of OB-RL expression in hypothalamus inhibits heterothermic regulation of bats, and also provided the clues for further analyzing the mechanism of Leptin in the heterothermic regulation of mammals.

Harnessing TME depicted by histological images to improve cancer prognosis through a deep learning system.

Spatial transcriptomics (ST) provides insights into the tumor microenvironment (TME), which is closely associated with cancer prognosis, but ST has limited clinical availability. In this study, we provide a powerful deep learning system to augment TME information based on histological images for patients without ST data, thereby empowering precise cancer prognosis. The system provides two connections to bridge existing gaps. The first is the integrated graph and image deep learning (IGI-DL) model, which predicts ST expression based on histological images with a 0.171 increase in mean correlation across three cancer types compared with five existing methods. The second connection is the cancer prognosis prediction model, based on TME depicted by spatial gene expression. Our survival model, using graphs with predicted ST features, achieves superior accuracy with a concordance index of 0.747 and 0.725 for The Cancer Genome Atlas breast cancer and colorectal cancer cohorts, outperforming other survival models. For the external Molecular and Cellular Oncology colorectal cancer cohort, our survival model maintains a stable advantage.

Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis.

Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Current understanding of the contribution of lactate to the cardiovascular system and its therapeutic relevance.

Research during the past decades has yielded numerous insights into the presence and function of lactate in the body. Lactate is primarily produced via glycolysis and plays special roles in the regulation of tissues and organs, particularly in the cardiovascular system. In addition to being a net consumer of lactate, the heart is also the organ in the body with the greatest lactate consumption. Furthermore, lactate maintains cardiovascular homeostasis through energy supply and signal regulation under physiological conditions. Lactate also affects the occurrence, development, and prognosis of various cardiovascular diseases. We will highlight how lactate regulates the cardiovascular system under physiological and pathological conditions based on evidence from recent studies. We aim to provide a better understanding of the relationship between lactate and cardiovascular health and provide new ideas for preventing and treating cardiovascular diseases. Additionally, we will summarize current developments in treatments targeting lactate metabolism, transport, and signaling, including their role in cardiovascular diseases.

Differences in right ventricular function and response to targeted therapy between patients with IPAH and PAH-CHD.

Background and aims: Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disorder characterized by elevated pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP). Right heart failure is a life-threatening complication of PAH and predicts a poor prognosis. PAH associated with congenital heart disease (PAH-CHD) and idiopathic PAH (IPAH) are two prevalent PAH subtypes in China. In this section, we set out to explore baseline right ventricular (RV) function and its response to targeted agents between IPAH and PAH-CHD. Methods and results: Consecutive patients diagnosed with IPAH or PAH-CHD by right heart catheterization (RHC) in the Second Xiangya Hospital from November 2011 to June 2020 were included. All patients received PAH-targeted therapy and the RV function was assessed by echocardiography at baseline and during follow-up. A total of 303 patients (age, 36.23 ± 13.10 years; women, 213 (70.3%); mean PAP [mPAP], 63.54 ± 16.12 mmHg; PVR, 14.74 ± 7.61 WU) with IPAH (n = 121) or PAH-CHD (n = 182) were included in this study. Compared with PAH-CHD, patients with IPAH had worse baseline RV function. As of the latest follow-up, forty-nine patients with IPAH and six patients with PAH-CHD died. Kaplan-Meier analyses showed better survival in PAH-CHD versus IPAH. After PAH-targeted therapy, patients with IPAH had less improvement in 6 MWD, World Health Organization functional class, and RV functional parameters compared with patients with PAH-CHD. Conclusion: Compared with patients with PAH-CHD, patients with IPAH had worse baseline RV function, unfavourable prognosis, and inadequate response to targeted treatment.

Association between blood heavy metals and lung cancer risk: A case-control study in China.

BACKGROUND: Exposure to various metals has been reported to lead to lung cancer. However, few studies focused on the combined effects of metal mixture. OBJECTIVE: To explore the relationship between metal mixture and lung cancer patients. METHODS: Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of 8 heavy metals (V, Cr, Mn, Se, Mo, Cd, Ba and Pb) in serum samples of 86 cases and 105 controls in the Tianjin Lung Cancer Cohort. Logistic regression models were used to estimate the effect of each metal on the risk of lung cancer. The restricted cubic spline function was applied to describe the dose-response relationship between various metal concentrations and lung cancer risk. Bayesian Kernel Machine Regression (BKMR), Weighted Quantile Sum (WQS) and Quantile G-Computation (QGC) were employed to explore the effects of metal mixtures as a whole on lung cancer. RESULTS: An increased risk of lung cancer was associated with higher blood Mo concentration (adjusted OR = 2.94, 95% CI = 1.03-8.74 for tertile 2 vs. tertile 1). Higher Se concentration in blood may have protective effects on the risk of lung cancer (adjusted OR = 0.18, 95% CI = 0.06-0.51 for tertile 3 vs. tertile 1, p-trend <0.001). In addition, Se and Cd may have an antagonism effect on the occurrence of lung cancer (RERI and 95% CI = -0.95 [-31.77, -0.07]; AP and 95% CI = -0.95 [-5.16 -0.74]). Although the metal mixture did not show a significant effect on lung cancer as a whole, this may be due to the offsetting effect between positive and negative effects. CONCLUSIONS: Our research indicates that Se has a promising anti-cancer application, but it is necessary to prevent the role of Cd that antagonize Se in lung cancer.

Super-assembly of integrated gold magnetic assay with loop-mediated isothermal amplification for point-of-care testing.

With the increasing global threat of various diseases and infections, it is essential to develop a fast, low-cost, and easy-to-use point-of-care testing (POCT) system for inspections at all levels of medical institutions and self-examination at home. In this work, gold magnetic nanoparticles (GMNPs) are used as the key material, and a rapid visual detection method is designed through integrating loop-mediated isothermal amplification (LAMP) and lateral flow assay (LFA) biosensor for detecting a variety of analytes which includes whole blood, buccal swabs, and DNA. It is worth to note that the proposed method does not need DNA extraction. Furthermore, uracil DNA glycosylase (UDG) is employed to eliminate carrier contamination for preventing false positive results. The whole detection process can be finished within 25 min. The accuracy of detection is measured by assessing the polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T. The detection limit of the newly developed extraction-free detection system for MTHFR C677T is 0.16 ng/µL. A preliminary clinical study of the proposed method is carried out by analyzing 600 clinical samples (including 200 whole blood samples, 100 buccal swabs, and 300 genomic DNA samples). The results indicate that the proposed method is 100% consistent with the sequencing results which provides a new choice for POCT and shows a broad application prospect in all levels of medical clinics and at home. Electronic Supplementary Material: Supplementary material (details for MTHFR C677T primer sequences, the cell count results of samples at different dilution ratios, genotyping results and frequency samples, a Hardy-Weinberg equilibrium test, the sensitivity of the system, detection results of multiple samples, and optimization of the system) is available in the online version of this article at 10.1007/s12274-022-4692-9.

Association of statin use and increase in lipoprotein(a): a real-world database research.

BACKGROUND: There is an increased concern that statins may have an unintended effect of elevated lipoprotein(a) [Lp(a)]. We conducted a large sample real-world study to test the association. METHODS: This retrospective cohort study was conducted using data from an integrated SuValue database, which includes 221 hospitals across China covering more than 200,000 of population with longitudinal follow-up to 10 years. Propensity score matching was applied to identify two comparable cohorts with statin users and non-statin users. Detailed follow-up information such as Lp(a) levels were extracted. The hazard ratio was calculated on Lp(a) changes based on the statin usage cohorts. Detailed subgroup and different characteristic cohorts' analyses were also conducted. RESULTS: After baseline propensity score matching, a total of 42,166 patients were included in a 1:1 matched ratio between statin users and non-statin users. In the case of no difference in low density lipoprotein (LDL-C), Lp(a) was increased significantly with the use of statins (adjusted HR 1.47; 95% confidence interval [CI] 1.43-1.50). Lp(a) increase was observed in various subgroup analyses and different cohorts. The dose intensity of statin was positively associated with the evaluated Lp(a) level. CONCLUSION: The use of statins was associated with an increased risk of Lp(a) elevation compared with non-statin use counterparts. The clinical relevance of these increases needs to be addressed in surrogate marker trials and/or large, cardiovascular outcomes trials.

Redetermination of Ce[B(5)O(8)(OH)(H(2)O)]NO(3)·2H(2)O.

The crystal structure of Ce[B(5)O(8)(OH)(H(2)O)]NO(3)·2H(2)O, cerium(III) aqua-hydroxidoocta-oxidopenta-borate nitrate dihydrate, has been redetermined from single-crystal X-ray diffraction data. In contrast to the previous determination [Li et al. (2003 ▶). Chem. Mater.15, 2253-2260], the present study reveals the location of all H atoms, slightly different fundamental building blocks (FBBs) of the polyborate anions, more reasonable displacement ellipsoids for all non-H atoms, as well as a model without disorder of the nitrate anion. The crystal structure is built from corrugated polyborate layers parallel to (010). These layers, consisting of [B(5)O(8)(OH)(H(2)O)](2-) anions as FBBs, stack along [010] and are linked by Ce(3+) ions, which exhibit a distorted CeO(10) coordination sphere. The layers are additionally stabilized via O-H⋯O hydrogen bonds between water mol-ecules and nitrate anions, located at the inter-layer space. The [BO(3)(H(2)O)]-group shows a [3 + 1] coordination and is considerably distorted from a tetra-hedral configuration. Bond-valence-sum calculation shows that the valence sum of boron is only 2.63 valence units (v.u.) when the contribution of the water mol-ecule (0.49 v.u.) is neglected.