Conditional knockout of ITGB4 in bronchial epithelial cells directs bronchopulmonary dysplasia.

Neonatal respiratory system disease is closely associated with embryonic lung development. Our group found that integrin ß4 (ITGB4) is downregulated in the airway epithelium of asthma patients. Asthma is the most common chronic respiratory illness in childhood. Therefore, we suspect whether the deletion of ITGB4 would affect fetal lung development. In this study, we characterized the role of ITGB4 deficiency in bronchopulmonary dysplasia (BPD). ITGB4 was conditionally knocked out in CCSP-rtTA, Tet-O-Cre and ITGB4f/f triple transgenic mice. Lung tissues at different developmental stages were collected for experimental detection and transcriptome sequencing. The effects of ITGB4 deficiency on lung branching morphogenesis were observed by fetal mouse lung explant culture. Deleting ITGB4 from the airway epithelial cells results in enlargement of alveolar airspaces, inhibition of branching, the abnormal structure of epithelium cells and the impairment of cilia growth during lung development. Scanning electron microscopy showed that the airway epithelial cilia of the ß4ccsp.cre group appear to be sparse, shortened and lodging. Lung-development-relevant factors such as SftpC and SOX2 significantly decreased both mRNA and protein levels. KEGG pathway analysis indicated that multiple ontogenesis-regulating-relevant pathways converge to FAK. Accordingly, ITGB4 deletion decreased phospho-FAK, phospho-GSK3ß and SOX2 levels, and the correspondingly contrary consequence was detected after treatment with GSK3ß agonist (wortmannin). Airway branching defect of ß4ccsp.cre mice lung explants was also partly recovered after wortmannin treatment. Airway epithelial-specific deletion of ITGB4 contributes to lung developmental defect, which could be achieved through the FAK/GSK3ß/SOX2 signal pathway.

Stable Lanthanide-Organic Frameworks: Crystal Structure, Photoluminescence, and Chemical Sensing of Vanillylmandelic Acid as a Biomarker of Pheochromocytoma.

Several isostructural lanthanide metal-organic frameworks, viz. [Ln(DCHB)1.5phen]n (Ln-MOFs, where Ln = Eu for 1, Tb for 2, Sm for 3 and Dy for 4), are successfully synthesized through the hydrothermal reactions of 4'-di(4-carboxylphenoxy)hydroxyl-2, 2'-bipyridyl (H2DCHB) and lanthanide nitrates as well as chelator 1,10-phenantroline (phen). These structures are characterized by single-crystal X-ray diffraction, and the representative Ln-MOF 1 is a fivefold interpenetrated framework with the uncoordinated Lewis base N sites form DCHB2- ligands. The photoluminescence research studies reveal that Ln-MOFs 1-4 exhibit characteristic fluorescent emissions from ligand-induced lanthanide Ln(III) ions, while the single-component emission spectra of Ln-MOF 4 are all located in a white region under different excitations. The absence of coordinated water and the interpenetration property of the structures are conducive to the structure rigidity, and the results display that Ln-MOF 1 has high thermal/chemical stabilities in common solvents and a wide pH range as well as the boiling water. Notably, luminescent sensing studies reveal that Ln-MOF 1 with prominent fluorescence properties can perform in highly sensitive and selective sensing of vanillylmandelic acid (VMA) in aqueous systems (KSV = 562.8 L·mol-1; LOD = 4.6 × 10-4 M), which can potentially establish a detection platform for the diagnosis of pheochromocytoma via multiquenching mechanisms. Moreover, the 1@MMMs sensing membranes comprised of Ln-MOF 1 and a poly(vinylidene fluoride) (PVDF) polymer can also be facilely developed for VMA detection in aqueous media, suggesting the enhanced convenience and efficiency of practical sensing applications.

Single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles in breast cancer.

BACKGROUND: In order to explore the surgical safety and the reliability of axillary staging of single-port endoscopic-sentinel lymph node biopsy, we combined it with indocyanine green that was excited by near-infrared fluorescence endoscopy and carbon nanoparticles as a tracer and compared this method to conventional open sentinel lymph node biopsy. METHODS: This is a retrospective and observational study, there were 20 patients in each group and the total sample size was 60: Group 1, single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles; Group 2, single-port endoscopic-sentinel lymph node biopsy with carbon nanoparticles only; Group 3, conventional sentinel lymph node biopsy with indocyanine green and carbon nanoparticles. Sentinel lymph node detection and upper extremity function were determined to measure the safety and efficacy of the novel single-port endoscopic-sentinel lymph node biopsy (SPE-SLNB) technique to the standard conventional sentinel lymph node biopsy technique. RESULTS: The detection rate of sentinel lymph nodes was 100% in Group 1, 100% in Group 2, and 95% in Group 3. There were no significant differences in upper arm function and pain scores between the three groups. CONCLUSION: The novel technique of combining indocyanine green and carbon nanoparticles with single-port endoscopic-sentinel lymph node biopsy achieved a similar detection rate and mean number of sentinel lymph nodes as conventional sentinel lymph node biopsy. Traditional open surgery requires two different incisions for breast surgery and SLNB. While the most important advantage of SPE-SLNB is that two procedures can be effectively performed through a single-port in the axilla Therefore, for patients who meet the indications, single-port endoscopic-sentinel lymph node biopsy is as safe and reliable as conventional sentinel lymph node biopsy but has the aesthetic advantage of only one incision.

Single-port nipple-sparing subcutaneous mastectomy with immediate prosthetic breast reconstruction for breast cancer.

INTRODUCTION: This study compares the perioperative results, aesthetic outcome and oncologic safety of single-port insufflation endoscopic nipple-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (SIE-NSM-IRPI) with those of conventional open-nipple and areola-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (C-NSM-IRPI). METHODS: In this retrospective cohort study, 64 early-stage breast cancer patients were divided into SIE-NSM-IRPI (n = 38) and C-NSM-IRPI (n = 26) groups. Perioperative results (operation time, intraoperative blood loss, incision length, drainage duration, and recent complications) were then compared between the two groups. Differences in satisfaction with the breasts, psychosocial well-being, physical well-being (chest) and sexual well-being were analyzed according to the BREAST-Q scale, and survival outcomes were also compared. RESULTS: The median follow-up time was 51.5 months. The incision length of SIE-NSM-IRPI was shorter than that of C-NSM-IRPI (P < 0.001). SIE-NSM-IRPI achieved the same detection rate and median number of sentinel lymph nodes as C-NSM-IRPI (3.00vs. 4.00, P = 0.780). The incidence of prosthesis removal due to infection or prosthesis exposure in the SIE-NSM-IRPI group was lower than that in the C-NSM-IRPI group (P = 0.015). Satisfaction with breasts (82.00vs.59.00, P < 0.001), psychosocial well-being (93.00vs.77.00, P = 0.001) and physical well-being (chest) (89.00vs.82.00, P < 0.001) scores were higher in the SIE-NSM-IRPI group. There were no significant differences between the two groups in disease-free survival (hazard ratio = 0.829, 95% confidence interval = 0.182-3.779) and overall survival (hazard ratio = 1.919, 95% confidence interval = 0.169-21.842). CONCLUSION: In this selected cohort of patients with early breast cancer, SIE-NSM-IRPI was comparable to C-NSM-IRPI, considering oncologic safety and detection of sentinel lymph nodes. It had a lower incidence of prosthesis removal, shorter incision length, and was associated with better patient satisfaction with the breasts. More random clinical trials of this novel approach in a larger cohort of Chinese patients with an extended follow-up period are needed in the future.

Comparing outcomes of single-port insufflation endoscopic breast-conserving surgery and conventional open approach for breast cancer.

BACKGROUND: In the surgical treatment of breast cancer, the goal of surgeons is to continually create and improve minimally invasive surgical techniques to increase patients' quality of life. Currently, routine breast-conserving surgery is often performed using two obvious incisions. Here, we compare the clinical efficacy and aesthetic outcomes of a novel technique using one incision, called 'single-port insufflation endoscopic breast-conserving surgery' (SIE-BCS), vs. conventional breast-conserving surgery (C-BCS) in patients with early-stage breast cancer. METHODS: A total of 180 patients with stage I or stage II breast cancer participated in this study, of whom 63 underwent SIE-BCS and 117 underwent C-BCS. Logistic regression analysis was conducted to assess the risk of local recurrence and metastasis. Aesthetic outcomes were evaluated using the BREAST-Q scale. RESULTS: The mean operation time was significantly longer for SIE-BCS (194.9 ± 71.5 min) than for C-BCS (140.3 ± 56.9 min), but the mean incision length was significantly shorter for SIE-BCS than for C-BCS (3.4 ± 1.2 cm vs. 8.6 ± 2.3 cm). While both surgeries yielded similar BREAST-Q ratings for satisfaction with breasts and sexual well-being, SIE-BCS was associated with significantly better ratings for physical well-being (chest area) and psychological well-being. Additionally, SIE-BCS was associated with decreased rates of adverse effects of radiation. The preliminary analysis showed that SIE-BCS did not increase the risk of local recurrence or metastasis. CONCLUSION: The novel single-port insufflation endoscopic assisted BCS technique is feasible, safe, and improves patients' postoperative comfort and psychological well-being, as compared to the conventional technique.

Tissue Sheet Engineered Using Human Umbilical Cord-Derived Mesenchymal Stem Cells Improves Diabetic Wound Healing.

Diabetic foot ulceration is a common chronic diabetic complication. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been widely used in regenerative medicine owing to their multipotency and easy availability. We developed poly(lactic-co-glycolic acid) (PLGA)-based scaffold to create hUC-MSC tissue sheets. In vitro immunostaining showed that hUC-MSC tissue sheets formed thick and solid tissue sheets with an abundance of extracellular matrix (ECM). Diabetic wounds in mice treated with or without either the hUC-MSC tissue sheet, hUC-MSC injection, or fiber only revealed that hUC-MSC tissue sheet transplantation promoted diabetic wound healing with improved re-epithelialization, collagen deposition, blood vessel formation and maturation, and alleviated inflammation compared to that observed in other groups. Taken collectively, our findings suggest that hUC-MSCs cultured on PLGA scaffolds improve diabetic wound healing, collagen deposition, and angiogenesis, and provide a novel and effective method for cell transplantation, and a promising alternative for diabetic skin wound treatment.

[Research progress of lung aging in chronic respiratory diseases].

Cell aging is an extremely complex process, which is characterized by mitochondrial structural dysfunction, telomere shortening, inflammatory microenvironment, protein homeostasis imbalance, epigenetic changes, abnormal DNA damage and repair, etc. Aging is usually accompanied by structural and functional damage of tissues and organs which further induces the occurrence and development of aging-related diseases. Aging includes physiological aging caused by increased age and pathological aging induced by a variety of factors. Noteworthy, as a target organ directly contacting with the outside air, lung is more prone to various stimuli, causing pathological premature aging which is lung aging. Studies have found that there is a certain proportion of senescent cells in the lungs of most chronic respiratory diseases. However, the underlying mechanism by which these senescent cells induce lung senescence and their role in chronic respiratory diseases is still obscure. This paper focuses on the causes and classification of lung aging, the internal mechanism of lung aging involved in chronic respiratory diseases, and the application of anti-aging treatments in chronic respiratory diseases. We hope to provide new research ideas and theoretical basis for the clinical prevention and treatment in chronic respiratory diseases.

Airway epithelial integrin ß4-deficiency exacerbates lipopolysaccharide-induced acute lung injury.

Airway epithelial cells, the first barrier of the respiratory tract, play an indispensable role in innate immunity. Integrin ß4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases and is downregulated in asthmatic patients. Research has shown that endothelial ITGB4 has proinflammatory properties in acute lung injury (ALI). However, the role of epithelial ITGB4 in a murine ALI model is still unknown. This study investigated the role of ITGB4 in lipopolysaccharide (LPS)-induced ALI. We found that ITGB4 in the airway epithelium had remarkably increased after the introduction of LPS in vivo and in vitro. Then, we constructed airway epithelial cell-specific ITGB4 knockout (ITGB4-/- ) mice to study its role in ALI. At a time point of 12 h after the tracheal injection of LPS, ITGB4-/- mice showed increased macrophages (mainly M1-type macrophages) and neutrophil infiltration into the lungs; inflammation-related proteins including interleukin (IL)-6, tumor necrosis factor, and IL-17A were significantly elevated compared to their levels in ITGB4+/+ mice. Furthermore, we investigated the role of ITGB4 in the anti-inflammatory response. Intriguingly, in the ITGB4-/- + LPS group, we found significantly reduced expression of anti-inflammatory factors, including IL-10 messenger RNA (mRNA) and ARG-1 mRNA. We also observed that monocyte chemotactic protein (MCP-1) increased significantly both in vivo and in vitro. Airway epithelium activates macrophages, most likely driven by MCP-1, which we confirmed in the coculture of epithelia and macrophages. These phenomena indicate that ITGB4 in airway epithelial cells plays an important role in the process of inflammation and activation of macrophages in ALI. Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in LPS-induced ALI.

Covalent-coordination tandem functionalization of a metal-organic framework (UiO-66) as a hybrid probe for luminescence detection of trans,trans-muconic acid as a biomarker of benzene and Fe3.

By means of post-synthetic treatment on the UiO-66 derivative with -SO3H, a novel luminescent hybrid material named Tb3+@UiO-66-SO3H has been prepared simply and efficiently. Given its wonderful luminescence properties like intense green emission, a long lifetime, a robust structure and photostability, it is further developed as a fluorescent probe for the sensing of trans,trans-muconic acid (tt-MA, a biomarker of benzene) and Fe3+, which are closely related to human health. Notably, Tb3+@UiO-66-SO3H shows an outstanding recognition ability for Fe3+ among common cations with a low detection limit (0.11 µM, 0.006 ppm). More importantly, Tb3+@UiO-66-SO3H can realize highly sensitive and selective detection of tt-MA (detection limit, 0.58 µM, 0.083 ppm). Besides, this rapid response probe is facilely prepared, non-toxic and reusable, showing the potential of Tb3+@UiO-66-SO3H in the practical monitoring of tt-MA and Fe3+.

A Stable Cd(II)-Based Metal-Organic Framework: Synthesis, Structure, and Its Eu3+ Functionalization for Ratiometric Sensing on the Biomarker 2-(2-Methoxyethoxy) Acetic Acid.

A novel two-dimensional Cd-based metal-organic framework (MOF), [Cd(pddb)H2O]n (Cd-MOF), has been hydrothermally synthesized using the V-shaped ligand 4,4'-(pyridine-2,6-diyl)-dibenzoic acid (H2pddb) and structurally characterized. The framework exhibits fascinating one-dimensional in-plane channels functionalized with active pyridine-N sites. The as-synthesized Cd-MOF exhibits excellent water and chemical stability. Furthermore, a simple and nondestructive coordinated postsynthetic modification method has been applied to Cd-MOF to obtain a class of MOF hybrids functionalized by lanthanide ions. More interestingly, Eu3+@Cd-MOF can act as a dual-emissive ratiometric fluorescent probe for 2-(2-methoxyethoxy) acetic acid (MEAA), a metabolite of 2-(2-methoxyethoxy) ethanol, which could result in DNA damage and teratogenic and developmental toxicity. During the sensing process, the fluorescence sensor exhibits notable water tolerance, reusability, and a low detection limit (8.5 µg mL-1). In addition, the chemical substances in human urine and serum do not interfere with the fluorescence quenching process, which makes it possible for the fluorescent probe to be applied in the detection of MEAA in human urine and serum systems. The possible sensing mechanism is also studied and discussed in detail.

A prognostic nomogram for long-term major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

BACKGROUND: Accurate prediction of major adverse cardiovascular events (MACEs) is very important for the management of acute coronary syndrome (ACS) patients. We aimed to construct an effective prognostic nomogram for individualized risk estimates of MACEs for patients with ACS after percutaneous coronary intervention (PCI). METHODS: This was a prospective study of patients with ACS after PCI from January 2013 to July 2019 (n = 2465). After removing patients with incomplete clinical information, a total of 1986 patients were randomly divided into evaluation (n = 1324) and validation (n = 662) groups. Predictors included in the nomogram were determined by a multivariate Cox proportional hazards regression model based on the training set. Receiver operating characteristic (ROC) curves and calibration curves were used to assess the discrimination and predictive accuracy of the nomogram, which were then compared with those of the classic models. The clinical utility of the nomogram was assessed by X-tile analysis and Kaplan-Meier curve analysis. RESULTS: Independent prognostic factors, including lactate level, age, left anterior descending branch stenosis, right coronary artery stenosis, brain natriuretic peptide level, and left ventricular ejection fraction, were determined and contained in the nomogram. The nomogram achieved good areas under the ROC curve of 0.712-0.762 in the training set and 0.724-0.818 in the validation set and well-fitted calibration curves. In addition, participants could be divided into two risk groups (low and high) according to this model. CONCLUSIONS: A simple-to-use nomogram incorporating lactate level effectively predicted 6-month, 1-year, and 4-year MACE incidence among patients with ACS after PCI.

[Research progress of respiratory syncytial virus (RSV) infection and respiratory diseases in infancy].

Lower respiratory tract infection (LRTI) induced by respiratory syncytial virus (RSV) is an important cause of hospitalization for infants. Compared with adults, infants are more likely to cause serious respiratory diseases after RSV infection due to the specific immature airway structure and immune system. The balance of immune resistance and immune tolerance of the host is critical to effective virus clearance and disease control. This paper reviews the relationship between RSV infection and respiratory diseases in infancy, the influence factors of the high pathogenicity of RSV infection in early life, as well as the research progress of anti-RSV therapy, and expands the specific molecular events regulating immune resistance and immune tolerance. We expect to present new ideas for the prevention and treatment of RSV-related respiratory diseases in clinical practice.

Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to determine the prognostic value of total tumor-infiltrating lymphocytes (TILs) and subtypes of TILs (CD4+, CD8+, and FOXP3+) in triple-negative breast cancer (TNBC). METHODS: A systematic search of the MEDLINE, EMBASE, and Web of Science databases was conducted to identified eligible articles published before August 2019. Study screening, data extraction, and risk of bias assessment were performed by two independent reviewers. Risk of bias on the study level was assessed using the ROBINS I tool and Quality in Prognosis Studies (QUIPS) tool. We performed a meta-analysis to obtain a pooled estimate of the prognostic role of TILs using Review Manager 5.3. RESULTS: In total, 37 studies were included in the final analysis. Compared to TNBC patients with low TIL levels, TNBC patients with high TIL levels showed a higher rate of pathological complete response (pCR) to treatment (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.43-3.19). With each 10% increase in percentage of TILs, patients with TNBC had an increased pCR (OR 1.09, 95% CI 1.02-1.16). Compared to TNBC patients with low TIL levels, patients with high TIL levels had better overall survival (OS; hazard ratio [HR] 0.58, 95% CI 0.48-0.71) and disease-free survival (DFS; HR 0.66, 95% CI 0.57-0.76). Additionally, with a continuous increase in TIL levels, patients with TNBC had improved OS (HR 0.90, 95% CI 0.87-0.93) and DFS (HR 0.92, 95% CI 0.90-0.95). A high CD4+ TIL level was associated with better OS (HR 0.49, 95% CI 0.32-0.76) and DFS (HR 0.54, 95% CI 0.36-0.80). A high CD8+ TIL level was associated better DFS only (HR 0.55, 95% CI 0.38-0.81), as no statistical association was found with OS (HR 0.70, 95% CI 0.46-1.06). A high FOXP3+ TIL level also was associated with only DFS (HR 0.50, 95% CI 0.33-0.75) and not OS (HR 1.28, 95% CI 0.24-6.88). CONCLUSIONS: TNBC with a high level of TILs showed better short-term and long-term prognoses. High levels of specific phenotypes of TILs (CD4+, CD8+, and FOXP3+) were predictive of a positive long-term prognosis for TNBC.

Cd-Based Metal-Organic Framework Containing Uncoordinated Carbonyl Groups as Lanthanide Postsynthetic Modification Sites and Chemical Sensing of Diphenyl Phosphate as a Flame-Retardant Biomarker.

With the judicious selection of an appropriate semirigid polycarboxylate, 2,5-bis(3',5'-dicarboxylphenyl)benzoic acid (H5bdba), and an inorganic metal ion, a novel anionic framework, {[NH2(CH3)2]2·[Cd3.5(bdba)(Hbdba)(H2O)1.5]}n (Cd-MOF), has been synthesized solvothermally. Single-crystal measurement results show that the prepared Cd-MOF features a three-dimensional structure containing two types of one-dimensional channels, and as we expected, there exist accessible uncoordinated -COOH groups on Hbdba pointing toward the rhombus channels. Powder X-ray diffraction and thermogravimetric analysis measurements were performed for the thermal and chemical stability analysis of Cd-MOF. In addition, the lanthanide(III)-functionalized hybrids, Ln(III)@Cd-MOF, were initially prepared by coordinated postsynthetic modification to incorporate luminescent Ln(III) ions into the structure. The luminescence properties of the hybrids are studied, and the results show notable and specialized fluorescent sensitization of Cd-MOF to Tb(III) ions. Moreover, the Tb(III)@Cd-MOF hybrid with outstanding fluorescence properties was developed as a highly sensitive and selective luminescent probe for the biomarker diphenyl phosphate (DPP) based on multiquenching effects. Tb(III)@Cd-MOF is the first case to realize the detection of urinary DPP through lanthanide metal-organic framework fluorescence spectrometry and shows practical detection potential.

Single-walled carbon nanotubes enhance the immune protective effect of a bath subunit vaccine for pearl gentian grouper against Iridovirus of Taiwan.

Iridovirus of Taiwan (TGIV) has been threatening the grouper farming since 1997, effective prophylaxis method is urgently needed. Subunit vaccine was proved to be useful to against the virus. Bath is the simplest method of vaccination and easy to be administrated without any stress to fish. In this research, we constructed a prokaryotic expression vector of TGIV's major capsid protein (MCP) to acquire the vaccine. Single-walled carbon nanotubes (SWCNTs) were used as the carrier to enhance the protective effect of bath vaccination for juvenile pearl gentian grouper (bath with concentrations of 5, 10, 20 mg/L for 6 h). Virus challenge was done after 28 days. Survival rates were calculated after 14 days. The level of antibody, activities of related enzymes in serums and expression of immune-related genes in kidneys and spleens were test. The results showed that vaccine with SWCNTs as carrier induced a higher level of antibody than that without. In addition, the activities of related enzymes (acid phosphatase, alkaline phosphatase, superoxide dismutase) and the expression of immune-related genes (Mx1, IgM, TNFαF, Lysozyme, CC chemokine 1, IL1-ß, IL-8) had a significantly increase. What's more, higher survival rates (42.10%, 77.77%, 89.47%) were provided by vaccine with SWCNTs than vaccine without SWCNTs (29.41%, 38.09%, 43.75%). This study suggests that the protective effect of vaccine that against TGIV with the method of bath vaccination could be enhanced by SWCNTs and SWCNTs could be a potential carrier for other subunit vaccines.

Comparison of platelet reactivity between prasugrel and ticagrelor in patients with acute coronary syndrome: a meta-analysis.

BACKGROUND: This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute coronary syndrome (ACS). METHODS: Eligible studies were retrieved from PubMed, Embase, and the Cochrane Library. HTPR and LTPR were evaluated on the basis of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) and P2Y12 reaction units (PRUs). HTPR and LTPR were analyzed using risk ratios (RRs) and their 95% confidence intervals (CIs). Weighted mean difference (WMD) and 95% CI were used to calculate the pooled effect size of platelet reactivity (PR). RESULTS: Fourteen eligible studies were obtained, which included 2629 patients treated with ticagrelor (n = 1340) and prasugrel (n = 1289). The pooled results showed that the prasugrel-treated patients had higher platelet reactivity than the ticagrelor-treated patients (PRU: WMD = - 32.26; 95% CI: - 56.48 to - 8.76; P < 0.01; VASP-PRI: WMD = - 9.61; 95% CI: - 14.63 to - 4.60; P = 0.002). No significant difference in HTPR based on PRU was identified between the ticagrelor and prasugrel groups (P = 0.71), whereas a lower HTPR based on VASP-PRI was found in the ticagrelor-treated patients than in the prasugrel-treated patients (RR = 0.30; 95% CI: 0.12-0.75; P = 0.010). In addition, the results showed a lower LTPR was observed in the prasugrel group than in the ticagrelor group (RR = 1.40; 95% CI: 1.08-1.81; P = 0.01). CONCLUSIONS: Prasugrel might enable higher platelet reactivity than ticagrelor. Ticagrelor could lead to a decrease in HTPR and increase in LTPR. However, this result was only obtained in pooled observational studies. Several uncertainties such as the nondeterminancy of the effectiveness of ticagrelor estimated using VASP-PRI or the definition of HTPR (a high or modifiable risk factor) might have affected our results.

Methylated Eu(III) metal-organic framework as a fluorescent probe for constructing molecular logic gates and monitoring of F-, I-, and S2.

A novel fluorescent and electron-deficient hybrid, N-methylated [Eu (pddb)phen(ox)0.5]n (Eu-MOF-Me) has been prepared via post-synthetic modification. Considering its special luminescent properties and cationic framework, Eu-MOF-Me is developed as a visualized fluorescent probe. Notably, water-stable Eu-MOF-Me exhibits advantages like good structural and fluorescent stability in a wide range of pH value (3.39-10.86), excellent identification ability for F-, I-, and S2- (it can easily distinguish F- and I- from other halogen ions and can realize naked eye identification of F-, I-, and S2-), relatively low detection limits (6.61 µM for S2-, 7.57 µM for F-), and reusability. More importantly, it has been utilized for the construction of a Boolean logic gate system. In this system, Eu-MOF-Me serves as the gate, by taking F-, I-, and S2- as the inputs and fluorescence emission bands (UV380, B437, and R612) as the outputs; some primary logic gates (NOR, IMP, YES, NOT) and the combination of them have been realized. Moreover, we achieved a cascaded logic gate (NOR+OR). For further application, a molecular computing keypad-lock security system has been obtained. Graphical abstract A novel fluorescent and electron-deficient hybrid named Eu-MOF-Me has been prepared via post-synthetic methylation. Considering its special luminescent properties and cationic framework, Eu-MOF-Me was developed as a fluorescent probe for the visual monitoring of important anions. In addition, it was used for the construction of Boolean logic library and a keypad-lock system was achieved.

Stable Tb(III)-Based Metal-Organic Framework: Structure, Photoluminescence, and Chemical Sensing of 2-Thiazolidinethione-4-carboxylic Acid as a Biomarker of CS2.

A novel three-dimensional microporous framework, [Tb(pddb)phen(ox)0.5] n (Tb-MOF), was synthesized hydrothermally with V-shaped 4,4'-(pyridine-2,6-diyl)dibenzoic acid (H2pddb), oxalate (ox), and 1,10-phenanthroline (phen). The framework of Tb-MOF features one-dimensional channels functionalized with pyridine-N Lewis base groups and the absence of coordinated and lattice water molecules in the structure. The Tb-MOF exhibits high thermostability (up to 385 °C) and chemical stability in a wide pH range (4-11) and common organic solvents as well as boiling water. The luminescence investigations of the Tb-MOF in common solvents, water with different pH values, and inorganic ions were performed. Results show that the Tb-MOF has high luminescence stability and the ability to probe Fe3+ ions. Significantly, the Tb-MOF with particularly high water stability can be first developed as a highly selective and sensitive luminescent sensor for the biomarker 2-thiazolidinethione-4-carboxylic acid (TTCA) via fluorescence quenching. The low detection limit (1 ppm), reusability, and high antidisturbance together make the Tb-MOF become a promising sensor for the practical detection of TTCA in urine systems, and for the first time realize the detection of urinary TTCA through fluorescence spectrometry based on an Ln-MOF sensor.

Serum relaxin level predicts recurrence of atrial fibrillation after radiofrequency catheter ablation.

Relaxin, an emerging biomarker in heart failure, is involved in fibrosis and inflammation. The value of relaxin in predicting recurrence of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) is unknown and the subject of this study. We prospectively enrolled 248 consecutive patients with AF (paroxysmal in 127 and persistent in 121) who underwent RFCA at our center after measurement of circulating levels of relaxin by ELISA. Kaplan-Meier analysis with log-rank test and multivariate analysis were used to assess the association between pre-RFCA relaxin levels and post-RFCA AF recurrence at 18 months follow-up. At mean 16.3 ± 3.8 months post-RFCA, 195 (78.6%) patients maintained sinus rhythm, and their pre-RFCA relaxin level was lower than that in patients with AF recurrence (P < 0.001). From lowest to highest pre-RFCA relaxin level tertiles (T1; 82.10-< 234.36; T2; 234.36-< 342.26; and T3; 342.26-740.63 ng/L), AF recurrence rate increased significantly (8.5%, 20.5% and 34.9%, respectively; Kaplan-Meier analysis with log-rank test, χ2 = 18.44, P < 0.001). Using a cutoff of 285.4 ng/L, pre-RFCA relaxin level predicted AF recurrence during follow-up with sensitivity of 77.4% and specificity of 55.9% (area under the receiver operating characteristic curve = 0.71). On multivariate Cox proportional hazard model, relaxin level by tertile (T2, hazard ratio 2.678; 95% confidence interval 1.110-6.460; P = 0.028, and T3, hazard ratio 4.745; 95% confidence interval 2.075-10.854; P < 0.001, respectively compared with the T1) was the independent factor predicting recurrence. Elevated pre-RFCA relaxin level is associated with post-RFCA AF recurrence. A simple measurement of relaxin level therefore might help identify patients at high risk of AF recurrence after RFCA.Clinical Trial Registration chictr.org.cn identifier: ChiCTR-OOC-15006130.

Outcomes of single-port gasless laparoscopic breast-conserving surgery for breast cancer: An observational study.

To compare the clinical efficacy and aesthetic perspectives between single-port gasless laparoscopic breast-conserving surgery (SGL-BCS) and traditional breast-conserving surgery (T-BCS) in early-stage breast cancer. A total of 70 patients who were diagnosed with stage I or stage II breast cancer participated in this study, which 35 patients underwent SGL-BCS, while others underwent T-BCS. There were no death or severe intraoperative complications, and none of the patients exhibited regional recurrence, distant metastases, or any critical complications after 2 years follow-up. SGL-BCS is feasible and safe surgery, and has advantages in terms of a single, shorter, hidden incision, high-satisficed aesthetic outcome and less intraoperative blood loss.