Gene-gene interaction network analysis indicates CNTN2 is a candidate gene for idiopathic generalized epilepsy.

Twin and family studies have established the genetic contribution to idiopathic generalized epilepsy (IGE). The genetic architecture of IGE is generally complex and heterogeneous, and the majority of the genetic burden in IGE remains unsolved. We hypothesize that gene-gene interactions contribute to the complex inheritance of IGE. CNTN2 (OMIM* 615,400) variants have been identified in cases with familial adult myoclonic epilepsy and other epilepsies. To explore the gene-gene interaction network in IGE, we took the CNTN2 gene as an example and investigated its co-occurrent genetic variants in IGE cases. We performed whole-exome sequencing in 114 unrelated IGE cases and 296 healthy controls. Variants were qualified with sequencing quality, minor allele frequency, in silico prediction, genetic phenotype, and recurrent case numbers. The STRING_TOP25 gene interaction network analysis was introduced with the bait gene CNTN2 (denoted as A). The gene-gene interaction pair mode was presumed to be A + c, A + d, A + e, with a leading gene A, or A + B + f, A + B + g, A + B + h, with a double-gene A + B, or other combinations. We compared the number of gene interaction pairs between the case and control groups. We identified three pairs in the case group, CNTN2 + PTPN18, CNTN2 + CNTN1 + ANK2 + ANK3 + SNTG2, and CNTN2 + PTPRZ1, while we did not discover any pairs in the control group. The number of gene interaction pairs in the case group was much more than in the control group (p = 0.021). Taking together the genetic bioinformatics, reported epilepsy cases, and statistical evidence in the study, we supposed CNTN2 as a candidate pathogenic gene for IGE. The gene interaction network analysis might help screen candidate genes for IGE or other complex genetic disorders.

A novel TCGA-validated programmed cell-death-related signature of ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is a gynecological malignancy tumor with high recurrence and mortality rates. Programmed cell death (PCD) is an essential regulator in cancer metabolism, whose functions are still unknown in OC. Therefore, it is vital to determine the prognostic value and therapy response of PCD-related genes in OC. METHODS: By mining The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Genecards databases, we constructed a prognostic PCD-related genes model and performed Kaplan-Meier (K-M) analysis and Receiver Operating Characteristic (ROC) curve for its predictive ability. A nomogram was created via Cox regression. We validated our model in train and test sets. Quantitative real-time PCR (qRT-PCR) was applied to identify the expression of our model genes. Finally, we analyzed functional analysis, immune infiltration, genomic mutation, tumor mutational burden (TMB) and drug sensitivity of patients in low- and high-risk group based on median scores. RESULTS: A ten-PCD-related gene signature including protein phosphatase 1 regulatory subunit 15 A (PPP1R15A), 8-oxoguanine-DNA glycosylase (OGG1), HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 (HERC1), Caspase-2.(CASP2), Caspase activity and apoptosis inhibitor 1(CAAP1), RB transcriptional corepressor 1(RB1), Z-DNA binding protein 1 (ZBP1), CD3-epsilon (CD3E), Clathrin heavy chain like 1(CLTCL1), and CCAAT/enhancer-binding protein beta (CEBPB) was constructed. Risk score performed well with good area under curve (AUC) (AUC3 - year =0.728, AUC5 - year = 0.730). The nomogram based on risk score has good performance in predicting the prognosis of OC patients (AUC1 - year =0.781, AUC3 - year =0.759, AUC5 - year = 0.670). Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that the erythroblastic leukemia viral oncogene homolog (ERBB) signaling pathway and focal adhesion were enriched in the high-risk group. Meanwhile, patients with high-risk scores had worse OS. In addition, patients with low-risk scores had higher immune-infiltrating cells and enhanced expression of checkpoints, programmed cell death 1 ligand 1 (PD-L1), indoleamine 2,3-dioxygenase 1 (IDO-1) and lymphocyte activation gene-3 (LAG3), and were more sensitive to A.443,654, GDC.0449, paclitaxel, gefitinib and cisplatin. Finally, qRT-PCR confirmed RB1, CAAP1, ZBP1, CEBPB and CLTCL1 over-expressed, while PPP1R15A, OGG1, CASP2, CD3E and HERC1 under-expressed in OC cell lines. CONCLUSION: Our model could precisely predict the prognosis, immune status and drug sensitivity of OC patients.

Glycometabolism and lipid metabolism related genes predict the prognosis of endometrial carcinoma and their effects on tumor cells.

BACKGROUND: Glycometabolism and lipid metabolism are critical in cancer metabolic reprogramming. The primary aim of this study was to develop a prognostic model incorporating glycometabolism and lipid metabolism-related genes (GLRGs) for accurate prognosis assessment in patients with endometrial carcinoma (EC). METHODS: Data on gene expression and clinical details were obtained from publicly accessible databases. GLRGs were obtained from the Genecards database. Through nonnegative matrix factorization (NMF) clustering, molecular groupings with various GLRG expression patterns were identified. LASSO Cox regression analysis was employed to create a prognostic model. Use rich algorithms such as GSEA, GSVA, xCELL ssGSEA, EPIC,CIBERSORT, MCPcounter, ESTIMATE, TIMER, TIDE, and Oncoppredict to analyze functional pathway characteristics of the forecast signal, immune status, anti-tumor therapy, etc. The expression was assessed using Western blot and quantitative real-time PCR techniques. A total of 113 algorithm combinations were combined to screen out the most significant GLRGs in the signature for in vitro experimental verification, such as colony formation, EdU cell proliferation, wound healing, apoptosis, and Transwell assays. RESULTS: A total of 714 GLRGs were found, and 227 of them were identified as prognostic-related genes. And ten GLRGs (AUP1, ESR1, ERLIN2, ASS1, OGDH, BCKDHB, SLC16A1, HK2, LPCAT1 and PGR-AS1) were identified to construct the prognostic model of patients with EC. Based on GLRGs, the risk model's prognosis and independent prognostic value were established. The signature of GLRGs exhibited a robust correlation with the infiltration of immune cells and the sensitivity to drugs. In cytological experiments, we selected HK2 as candidate gene to verify its value in the occurrence and development of EC. Western blot and qRT-PCR revealed that HK2 was substantially expressed in EC cells. According to in vitro experiments, HK2 knockdown can increase EC cell apoptosis while suppressing EC cell migration, invasion, and proliferation. CONCLUSION: The GLRGs signature constructed in this study demonstrated significant prognostic value for patients with endometrial carcinoma, thereby providing valuable guidance for treatment decisions.

Reductive Oxy-Nazarov Cyclization toward Expedient Construction of a Cyclopenta[1,2-b]pyrrolo[1,2-a]azepine Ring System: Formal Total Syntheses of Stemonamine and Cephalotaxine.

Formal total syntheses of stemonamine and cephalotaxine bearing the core cyclopenta[1,2-b]pyrrolo[1,2-a]azepine ring skeleton were achieved. The general synthetic strategy in the synthesis features the reductive oxy-Nazarov cyclization as key step, leading to the versatile construction of N-substituted spiro quaternary stereogenic centers from readily available starting materials.

Fast detection of hypobromous acid in cells and the water environment using a lysosome-targeted fluorescent probe.

A new fluorescent probe SWJT-23 with lysosomal targeting ability for detection of hypobromous acid (HBrO) was synthesised based on the naphthalimide skeleton. This probe exhibited a fast response (within 3s), a low detection limit (1.24 nM), excellent selectivity and a high fluorescence quantum yield (Φ = 0.490). Moreover, SWJT-23 not only realized the sensitive detection of HBrO in cells and water samples, but also was fabricated as a paper-based sensor. In consequence, SWJT-23 is expected to be an efficient and powerful tool for monitoring HBrO in organisms and the environment in realistic scenarios.

Cyanide-Isolated Cobalt Catalyst for Ultraefficient Advanced Oxidation Treatment.

Catalyst design with a "Co-N-C" structure at the atomic level has shown great interest for peroxymonosulfate (PMS) activation toward advanced oxidation water treatment. Here, we present an innovative way of producing cobalt hexacyanocobaltate (Co-HCC) with an abundance of atomically isolated CoII-NC sites at the outer surface. This material allows ultraefficient PMS activation to generate plenty of sulfate and hydroxyl radicals, with a turnover frequency much higher than those of most cobalt-based catalysts reported so far and even the homogeneous catalysis by Co2+ ions. We gained fundamental insights on its unprecedently high catalytic performance based on experimental results and computational study. Then, we controlled the growth of Co-HCC on a ceramic membrane to form a confined oxidation environment that utilizes the extended surface area and maximal exposure of short-lived radicals for a fast removal of organic pollutants that enter the pores. As a result, this catalytic membrane achieves complete disruption of micropollutants under a water flux up to 10,000 LMH (merely 0.2 s retention time) and further >90% mineralization of organic pollutants in complex industrial wastewater matrices (<100 s retention time), together with the merits of operational simplicity and great longevity (2 weeks continuous run). Our study elicits a new milestone in "Co-N-C" catalyst structure design for PMS activation and highlights the great interest of producing catalytic membranes for a confined treatment of organic pollutants from partial oxidation to complete mineralization as a new benchmark.

Potential Markers to Differentiate Uterine Leiomyosarcomas from Leiomyomas.

Uterine leiomyomas (ULM) are the most common benign tumors of the female genitalia, while uterine leiomyosarcomas (ULMS) are rare. The sarcoma is diffuse growth, prone to hematogenous metastasis, and has a poor prognosis. Due to their similar clinical symptoms and morphological features, it is sometimes difficult to distinguish them, and the final diagnosis depends on histological diagnosis. Misdiagnosis of ULM as ULMS will lead to more invasive and extensive surgery when it is not needed, while misdiagnosis of ULMS as ULM may lead to delayed treatment and poor prognosis. This review searched and studied the published articles on ULM and ULMS, and summarized the potential markers for the differential diagnosis of ULMS. These markers will facilitate differential diagnosis and personalized treatment, providing timely diagnosis and potentially better prognosis for patients.

Comprehensive analyses of mitophagy-related genes and mitophagy-related lncRNAs for patients with ovarian cancer.

BACKGROUND: Both mitophagy and long non-coding RNAs (lncRNAs) play crucial roles in ovarian cancer (OC). We sought to explore the characteristics of mitophagy-related gene (MRG) and mitophagy-related lncRNAs (MRL) to facilitate treatment and prognosis of OC. METHODS: The processed data were extracted from public databases (TCGA, GTEx, GEO and GeneCards). The highly synergistic lncRNA modules and MRLs were identified using weighted gene co-expression network analysis. Using LASSO Cox regression analysis, the MRL-model was first established based on TCGA and then validated with four external GEO datasets. The independent prognostic value of the MRL-model was evaluated by Multivariate Cox regression analysis. Characteristics of functional pathways, somatic mutations, immunity features, and anti-tumor therapy related to the MRL-model were evaluated using abundant algorithms, such as GSEA, ssGSEA, GSVA, maftools, CIBERSORT, xCELL, MCPcounter, ESTIMATE, TIDE, pRRophetic and so on. RESULTS: We found 52 differentially expressed MRGs and 22 prognostic MRGs in OC. Enrichment analysis revealed that MRGs were involved in mitophagy. Nine prognostic MRLs were identified and eight optimal MRLs combinations were screened to establish the MRL-model. The MRL-model stratified patients into high- and low-risk groups and remained a prognostic factor (P < 0.05) with independent value (P < 0.05) in TCGA and GEO. We observed that OC patients in the high-risk group also had the unfavorable survival in consideration of clinicopathological parameters. The Nomogram was plotted to make the prediction results more intuitive and readable. The two risk groups were enriched in discrepant functional pathways (such as Wnt signaling pathway) and immunity features. Besides, patients in the low-risk group may be more sensitive to immunotherapy (P = 0.01). Several chemotherapeutic drugs (Paclitaxel, Veliparib, Rucaparib, Axitinib, Linsitinib, Saracatinib, Motesanib, Ponatinib, Imatinib and so on) were found with variant sensitivity between the two risk groups. The established ceRNA network indicated the underlying mechanisms of MRLs. CONCLUSIONS: Our study revealed the roles of MRLs and MRL-model in expression, prognosis, chemotherapy, immunotherapy, and molecular mechanism of OC. Our findings were able to stratify OC patients with high risk, unfavorable prognosis and variant treatment sensitivity, thus improving clinical outcomes for OC patients.

Whole-transcriptome defines novel glucose metabolic subtypes in colorectal cancer.

Colorectal cancer (CRC) is the most prevalent malignancy of the digestive system. Glucose metabolism plays a crucial role in CRC development. However, the heterogeneity of glucose metabolic patterns in CRC is not well characterized. Here, we classified CRC into specific glucose metabolic subtypes and identified the key regulators. 2228 carbohydrate metabolism-related genes were screened out from the GeneCards database, 202 of them were identified as prognosis genes in the TCGA database. Based on the expression patterns of the 202 genes, three metabolic subtypes were obtained by the non-negative matrix factorization clustering method. The C1 subtype had the worst survival outcome and was characterized with higher immune cell infiltration and more activation in extracellular matrix pathways than the other two subtypes. The C2 subtype was the most prevalent in CRC and was characterized by low immune cell infiltration. The C3 subtype had the smallest number of individuals and had a better prognosis, with higher levels of NRF2 and TP53 pathway expression. Secreted frizzled-related protein 2 (SFRP2) and thrombospondin-2 (THBS2) were confirmed as biomarkers for the C1 subtype. Their expression levels were elevated in high glucose condition, while their knockdown inhibited migration and invasion of HCT 116 cells. The analysis of therapeutic potential found that the C1 subtype was more sensitive to immune and PI3K-Akt pathway inhibitors than the other subtypes. To sum up, this study revealed a novel glucose-related CRC subtype, characterized by SFRP2 and THBS2, with poor prognosis but possible therapeutic benefits from immune and targeted therapies.

RF-induced heating for active implantable medical devices in dual parallel leads configurations at 1.5 T MRI.

PURPOSE: The Radiofrequency (RF)-induced heating for an active implantable medical device (AIMD) with dual parallel leads is evaluated in this paper. The coupling effects between dual parallel leads are studied via simulations and experiments methods. The global transfer function technique is used to assess the RF-induced heating for dual-lead AIMDs inside four human body models. METHODS: RF-induced heating for spinal cord stimulator systems with 60 and 90 cm length leads are studied at three parallel dual-lead configurations (closely spaced, 8 mm spaced, and 40 mm spaced) and a single-lead configuration. The global transfer function method is used to develop the AIMD models of different configurations and is used for lead-tip heating assessments inside human body models. RESULTS: In simulation studies, the peak 1g specific absorption rate/temperatrue rises of dual parallel leads systems is lower than those from the single-lead system. In experimental American Society for Testing and Materials phantom studies, the temperature rises for the single-lead AIMD system can be 2.4 times higher than that from dual-lead AIMD systems. For the spinal cord stimulator systems used in the study, the statistical analysis shows the RF-induced heating of dual-lead configurations are also lower than those from the single-lead configuration inside all four human body models. CONCLUSION: For the AIMD system in this study, it shows that the coupling effects between the dual parallel leads of AIMD systems can reduce RF-induced heating. The global transfer function for different spatial distance dual-lead configurations can potentially provide a method for the RF-induced heating evaluation for dual-lead AIMD systems.

Chromatic aberration correction based on cross-channel information alignment in microscopy.

A microscope usually consists of dozens of complex lenses and requires careful assembly, alignment, and testing before use. Chromatic aberration correction is a significant step in the design of microscopes. Reducing chromatic aberration by improving optical design will inevitably increase the overall weight and size of the microscope, leading to more cost in manufacturing and maintenance. Nevertheless, the improvement in hardware can only achieve limited correction. In this paper, we propose an algorithm based on cross-channel information alignment to shift some of the correction tasks from optical design to post-processing. Additionally, a quantitative framework is established to evaluate the performance of the chromatic aberration algorithm. Our algorithm outperforms the other state-of-the-art methods in both visual appearance and objective assessments. The results indicate that the proposed algorithm can effectively obtain higher-quality images without changing the hardware or engaging the optical parameters.

Concise Total Synthesis of (-)-Quinocarcin Enabled by Catalytic Enantioselective Reductive 1,3-Dipolar Cycloaddition of Secondary Amides.

A concise asymmetric total synthesis of (-)-quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3-dipolar cycloaddition reaction of N-heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio-, exo- and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a RhIII -catalyzed C-H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline-pyrrolidine tetracyclic core unit of quinocarcin.

Body-loop related MRI radiofrequency-induced heating hazards: Observations, characterizations, and recommendations.

PURPOSE: To assess RF-induced heating hazards in 1.5T MR systems caused by body-loop postures. METHODS: Twelve advanced high-resolution anatomically correct human body models with different body-loop postures are created based on poseable human adult male models. Numerical simulations are performed to assess the radiofrequency (RF)-induced heating of these 12 models at 11 landmarks. A customized phantom is developed to validate the numerical simulations and quantitatively analyze factors affecting the RF-induced heating, eg, the contact area, the loop size, and the loading position. The RF-induced heating inside three differently posed phantoms is measured. RESULTS: The RF-induced heating from the body-loop postures can be up to 11 times higher than that from the original posture. The RF-induced heating increases with increasing body-loop size and decreasing contact area. The magnetic flux increases when the body-loop center and the RF coil isocenter are close to each other, leading to increased RF-induced heating. An air gap created in the body loop or generating a polarized magnetic field parallel to the body loop can reduce the heating by a factor of three at least. Experimental measurements are provided, validating the correctness of the numerical results. CONCLUSION: Safe patient posture during MR examinations is recommended with the use of insulation materials to prevent loop formation and consequently avoiding high RF-induced heating. If body loops cannot be avoided, the body loop should be placed outside the RF transmitting coil. In addition, linear polarization with magnetic fields parallel to the body loop can be used to circumvent high RF-induced heating.

A technique for the reduction of RF-induced heating of active implantable medical devices during MRI.

PURPOSE: The paper presents a novel method to reduce the RF-induced heating of active implantable medical devices during MRI. METHODS: With the addition of an energy decoying and dissipating structure, RF energy can be redirected toward the dissipating rings through the decoying conductor. Three lead groups (45 cm-50 cm) and 4 (50 cm-100 cm) were studied in 1.5 Tesla MR systems by simulation and measurement, respectively. In vivo modeling was performed using human models to estimate the RF-induced heating of an active implantable medical device for spinal cord treatment. RESULT: In the simulation study, it was shown that the peak 1g-averaged specific absorption rate near the lead-tips can be reduced by 70% to 80% compared to those from the control leads. In the experimental measurements during a 2-min exposure test in a 1.5 Telsa MR system, the temperature rises dropped from the original 18.3℃, 25.8℃, 8.1℃, and 16.1℃ (control leads 1-4) to 5.4℃, 6.9℃, 1.6℃, and 3.3℃ (leads 1-4 with the energy decoying and dissipation structure). The in vivo calculation results show that the maximum induced temperature rise among all cases can be substantially reduced (up to 80%) when the energy decoying and dissipating structures were used. CONCLUSION: Our studies confirm the effectiveness of the novel technique for a variety of scanning scenarios. The results also indicate that the decoying conductor length, number of rings, and ring area must be carefully chosen and validated.

Magnetic resonance conditionality of abandoned leads from active implantable medical devices at 1.5 T.

PURPOSE: During MR scans, abandoned leads from active implantable medical devices (AIMDs) can experience excessive heating at the lead tip, depending on the type of termination applied to the proximal contacts (proximal end treatment). The influence of different proximal end treatments (ie, [1] freely exposed in the tissue, [2] terminated with metal in contact with the tissue, or [3] capped with plastic, and thereby fully insulated, on the RF-induced lead-tip heating) are studied. A technique to ensure that MR Conditional AIMD leads remain MR Conditional even when abandoned is recommended. METHODS: Abandoned leads from three MR Conditional AIMDs ([1] a sacral neuromodulation system, [2] a cardiac rhythm management pacemaker system, and [3] a deep brain stimulator system) were investigated in this study. The computational lead models (ie, the transfer functions) for different proximal end treatments were measured and used to assess the in vivo lead-tip heating for four virtual human models (FATS, Duke, Ella, and Billie) and compared with the lead-tip heating of the complete MR Conditional AIMD system. RESULT: The average and maximum lead-tip heating for abandoned leads proximally capped with metal is always lower than that from the complete AIMD system. Abandoned leads proximally insulated could lead to an average in vivo temperature rise up to 3.5 times higher than that from the complete AIMD system. CONCLUSION: For the three investigated AIMDs under 1.5T MR scanning, our results indicate that RF-induced lead-tip heating of abandoned leads strongly depends on the proximal lead termination. A metallic cap applied to the proximal termination of the tested leads could significantly reduce the RF-induced lead-tip heating.

A comprehensive pan-cancer analysis of necroptosis molecules in four gynecologic cancers.

BACKGROUND: In recent years, it has been proved that necroptosis plays an important role in the occurrence, development, invasion, metastasis and drug resistance of malignant tumors. Hence, further evaluation and targeting of necroptosis may be of clinical benefit for gynecologic cancers (GCs). METHODS: To compare consistency and difference, we explored the expression pattern and prognostic value of necroptosis-related genes (NRGs) in pan-GC analysis through Linear regression and Empirical Bayesian, Univariate Cox analysis, and public databases from TCGA and Genotype-Tissue Expression (GTEx), including CESC, OV, UCEC, and UCS. We explored the copy number variation (CNV), methylation level and enrichment pathways of NRGs in the four GCs. Based on LASSO Cox regression analysis or principal component analysis, we established the prognostic NRG-signature or necroptosis-score for the four GCs. In addition, we predicted and compared functional pathways, tumor mutational burden (TMB), somatic mutation features, immunity status, immunotherapy, chemotherapeutic drug sensitivity of the NRG-signature based on NRGs. We also examined the expression level of several NRGs in OV samples that we collected using Quantitative Real-time PCR. RESULTS: We confirmed the presence of NRGs in expression, prognosis, CNV, and methylation for four GCs, thus comparing the consistency and difference among the four GCs. The prognosis and independent prognostic value of the risk signatures based on NRGs were determined. Through the results of subclass mapping, we found that GC patients with lower risk score may be more sensitive to PDL1 response and more sensitive to immune checkpoint blockade therapy. Drug susceptibility analysis showed that, 51, 45, 64, and 29 drugs with differences between risk groups were yielded in CESC, OV, UCEC, and UCS respectively. For OV, the expression differences of several NRGs in the tissues we collected were similar to that in TCGA. CONCLUSION: Our comprehensive analysis of NRGs and NRG-signature demonstrated their similarity and difference, as well as their potential roles in prognosis and could guide therapeutic strategies, thus improving the outcome of GC patients.

Rapid sensing and imaging of methylglyoxal in living cells enabled by a near-infrared fluorescent probe.

A novel near-infrared fluorescent probe (SWJT-2) has been designed and synthesized for the detection of methylglyoxal (MGO). It showed a low detection limit (0.32 µM), high selectivity and the fastest detection (15 min) over various reactive carbonyl compounds in aqueous solution. SWJT-2 had been successfully applied to bioimaging in HeLa cells to detect exogenous and endogenous MGO.

Clopidogrel versus ticagrelor in East Asian patients aged 75 years or older with acute coronary syndrome: observations from the GF-APT registry.

The benefits of potent antithrombotic therapy usually come at the expense of a higher risk of bleeding. The efficacy and safety of ticagrelor in elderly East Asian populations remains debated due to the concerns about the imbalance of ischemic and bleeding risks. This study aimed to compare the impact of clopidogrel with ticagrelor on clinical outcomes in East Asian patients aged ≥75 years with acute coronary syndrome (ACS) using data from an institutional registry. We assessed the treatment effect of ticagrelor versus clopidogrel based on propensity scores and multivariate Cox proportional hazards models. A total of 2775 ACS patients were included, of which 235 (8.5%) were treated with ticagrelor. The primary efficacy outcome occurred in 11.9% of patients treated with ticagrelor versus 8.8% treated with clopidogrel. There was no significant association between treatment with ticagrelor and a lower risk of the primary efficacy outcome (p = .156). However, the incidences of all-cause death (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.02 to 2.79) and major bleeding (adjusted HR 2.20, 95% CI 1.06 to 4.56) were significantly higher in patients treated with ticagrelor than clopidogrel. In elderly patients with ACS from East Asia, the efficacy of clopidogrel was comparable to ticagrelor, while ticagrelor is associated with an increased risk of mortality and major bleeding.

What is the context?Current guidelines recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS).There are no specific guidelines concerning the elderly, and data on optimal antiplatelet therapy in elderly are quite scarce.Further study was necessary to identify the efficacy and safety of ticagrelor and clopidogrel in elderly patients from East Asian populations which are reported to be at a higher risk of bleeding.What is new?The risk of major adverse cardiac events did not differ significantly between clopidogrel versus ticagrelor in patients aged ≥75 years from East Asia, while the use of ticagrelor might be associated with increased risk of mortality and major bleeding events.Analyses after propensity score matching showed consistent results on the safety and efficacy of clopidogrel versus ticagrelor.The benefit of potent P2Y₁₂ inhibitor ticagrelor over clopidogrel is questionable in elderly East Asian patients with ACS.What is the impact? This study provides more information on the use of potent antiplatelet therapy in older patients from Asia. The individual assessment of ischemic and bleeding risk is necessary to guide decision-making on DAPT rather than applying the recommendations of guidelines directly.

An innovative surgical approach: suture fixation of the levonorgestrel-releasing intrauterine system in the treatment of adenomyosis.

BACKGROUND: Placement of a levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective treatment for adenomyosis, especially for patients who have severe dysmenorrhea symptoms but a strong desire to preserve fertility. Nonetheless, for patients with adenomyosis accompanied by an enlarged uterus, expulsion of the ring is a troublesome problem. In this study, we sewed and fixed the LNG-IUS in the uterus, which provides a good solution to this problem. METHODS: In this prospective case series approved by the Ethics Committee of Hangzhou Women's Hospital, 12 patients with adenomyosis were successfully enrolled after providing informed consent, and all patients underwent long-term postoperative follow-up. RESULTS: Twelve patients with adenomyosis underwent suture fixation with an LNG-IUS, and during the long-term postoperative follow-up, every patient experienced complete remission of their symptoms: a significant decrease in menstrual flow, relief of dysmenorrhea, and improvement in quality of life. Only one person reported expulsion a year later. CONCLUSION: In patients with adenomyosis suffering from dysmenorrhea or excessive menstrual blood loss, suture fixation of an LNG-IUS using the hysteroscopic cold knife surgery system is a minimally invasive and effective alternative treatment for adenomyosis and decreases the risk of LNG-IUS expulsion.

Additional value of deep learning computed tomographic angiography-based fractional flow reserve in detecting coronary stenosis and predicting outcomes.

BACKGROUND: Deep learning (DL) has achieved great success in medical imaging and could be utilized for the non-invasive calculation of fractional flow reserve (FFR) from coronary computed tomographic angiography (CCTA) (CT-FFR). PURPOSE: To examine the ability of a DL-based CT-FFR in detecting hemodynamic changes of stenosis. MATERIAL AND METHODS: This study included 73 patients (85 vessels) who were suspected of coronary artery disease (CAD) and received CCTA followed by invasive FFR measurements within 90 days. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristics curve (AUC) were compared between CT-FFR and CCTA. Thirty-nine patients who received drug therapy instead of revascularization were followed for up to 31 months. Major adverse cardiac events (MACE), unstable angina, and rehospitalization were evaluated and compared between the study groups. RESULTS: At the patient level, CT-FFR achieved 90.4%, 93.6%, 88.1%, 85.3%, and 94.9% in accuracy, sensitivity, specificity, PPV, and NPV, respectively. At the vessel level, CT-FFR achieved 91.8%, 93.9%, 90.4%, 86.1%, and 95.9%, respectively. CT-FFR exceeded CCTA in these measurements at both levels. The vessel-level AUC for CT-FFR also outperformed that for CCTA (0.957 vs. 0.599, P < 0.0001). Patients with CT-FFR ≤0.8 had higher rates of rehospitalization (hazard ratio [HR] 4.51, 95% confidence interval [CI] 1.08-18.9) and MACE (HR 7.26, 95% CI 0.88-59.8), as well as a lower rate of unstable angina (HR 0.46, 95% CI 0.07-2.91). CONCLUSION: CT-FFR is superior to conventional CCTA in differentiating functional myocardial ischemia. In addition, it has the potential to differentiate prognoses of patients with CAD.