A Multimodal Meta-Analysis of Structural and Functional Alterations in the Brain of Knee Osteoarthritis Systematic Review.

BACKGROUND: Abnormalities of structural and functional brain regions might influence the persistence of knee pain, the progression, and the response to treatments in knee osteoarthritis (KOA). These complex alterations present a challenge to the understanding of its mechanism. OBJECTIVES: To meta-analyze the concurrence across structural and functional magnetic resonance imaging studies. STUDY DESIGN: Systematic review and meta-analysis. SETTING: This meta-analysis examined all voxel-based morphometric (VBM) and amplitude of low-frequency fluctuation (ALFF) studies involving the whole-brain alterations of KOA. METHODS: VBM and ALFF studies published up to May 7, 2023, were searched in the Web of Science, PubMed, EMBASE, Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database, Chongqing VIP, Wanfang Database. Two independent researchers carried out study screening, quality assessment, clinical data extraction, and neuroimaging data extraction. The whole-brain voxel-based gray matter (GM) and brain activity data of KOA were collected from eligible studies and meta-analyzed using the anisotropic effect size-signed differential mapping (AES-SDM). RESULTS: Fourteen studies were included in this study. In VBM meta-analyses, a total of 481 patients were enrolled in this study (252 KOA and 229 healthy patients). In the ALFF meta-analysis, a total of 518 patients were enrolled in this study (265 KOA and 253 healthy patients). According to the meta-analysis, KOA had increased GM volume in the right inferior frontal gyrus and decreased GM volume in the bilateral superior frontal gyrus, as well as increased brain activity in the left inferior frontal gyrus and inferior temporal gyrus, and decreased brain activity in the left middle occipital gyrus, right supramarginal gyrus, right superior frontal gyrus, and right superior parietal gyrus compared with healthy patients. LIMITATIONS: Most of the ALFF studies included in this meta-analysis were conducted in China. Our findings are exclusively addressed by the VBM and ALFF studies. The meta-regression between the duration of KOA, pain intensity and abnormal gray matter, and functional activity of brain regions in patients with KOA were unable to be analyzed. CONCLUSION: The results of this meta-analysis indicate that patients with KOA present significant abnormalities in GM volume and functional activity. These findings contribute to a better understanding of the structural and functional abnormalities seen in patients with KOA.

Occurrence and prevention of incisional hernia following laparoscopic colorectal surgery.

Among minimally invasive surgical procedures, colorectal surgery is associated with a notably higher incidence of incisional hernia (IH), ranging from 1.7% to 24.3%. This complication poses a significant burden on the healthcare system annually, necessitating urgent attention from surgeons. In a study published in the World Journal of Gastrointestinal Surgery, Fan et al compared the incidence of IH among 1614 patients who underwent laparoscopic colorectal surgery with different extraction site locations and evaluated the risk factors associated with its occurrence. This editorial analyzes the current risk factors for IH after laparoscopic colorectal surgery, emphasizing the impact of obesity, surgical site infection, and the choice of incision location on its development. Furthermore, we summarize the currently available preventive measures for IH. Given the low surgical repair rate and high recurrence rate associated with IH, prevention deserves greater research and attention compared to treatment.

Outcomes of advanced care management in home-based long-term care: A retrospective population-based observational study.

BACKGROUND: In home-based long-term care, care management aims to facilitate the independence of community-dwelling older adults and mitigate the escalation of their care needs. We examined the association between the types of care management (advanced vs. conventional) and the progression of care needs among recipients with moderate care needs and compared care services offered in care plans between care management types. METHODS: A retrospective, population-based observational study was conducted in Tsukuba City in Japan. The individual-level secondary data from the suburban municipal government was collected between May 2015 and March 2019. The primary outcome was the progression of care-need levels certificated in Japanese long-term care insurance. The exposure variable was advanced care management. First, we conducted propensity-score matching to adjust for differences in recipient characteristics. Second, we performed Kaplan-Meier survival analyses and log-rank tests, with the outcome measure being the progression of care-need levels. Third, Pearson's chi-square tests were performed to compare care services for recipients of advanced vs. conventional care management. RESULTS: Of the 1010 long-term care recipients, we selected 856 propensity score-matched recipients receiving advanced or conventional care management. The proportions of four-year cumulative progression-free survival in the groups receiving advanced and conventional care management were 82.2 % and 78.5 %, respectively (p = .69). The proportions of the groups with advanced and conventional care management were 17.1 % and 23.8 % using home-help services (p < .05), and 4.0 % and 8.2 % using community-based day care services (p < .05), respectively. CONCLUSIONS: Advanced care management in home-based long-term care was not associated with a slowing of the progression of care needs among older adults with moderate care needs compared with conventional care management. There was a notable discrepancy in the use of care services, with the advanced care management group having lower rates of use of home-help services and community-based day care services compared with the conventional care management group.

Kick-starting the zygotic genome: licensors, specifiers, and beyond.

Zygotic genome activation (ZGA), the first transcription event following fertilization, kickstarts the embryonic program that takes over the control of early development from the maternal products. How ZGA occurs, especially in mammals, is poorly understood due to the limited amount of research materials. With the rapid development of single-cell and low-input technologies, remarkable progress made in the past decade has unveiled dramatic transitions of the epigenomes, transcriptomes, proteomes, and metabolomes associated with ZGA. Moreover, functional investigations are yielding insights into the key regulators of ZGA, among which two major classes of players are emerging: licensors and specifiers. Licensors would control the permission of transcription and its timing during ZGA. Accumulating evidence suggests that such licensors of ZGA include regulators of the transcription apparatus and nuclear gatekeepers. Specifiers would instruct the activation of specific genes during ZGA. These specifiers include key transcription factors present at this stage, often facilitated by epigenetic regulators. Based on data primarily from mammals but also results from other species, we discuss in this review how recent research sheds light on the molecular regulation of ZGA and its executors, including the licensors and specifiers.

Epigenomic landscapes during prefrontal cortex development and aging in rhesus.

The prefrontal cortex (PFC) is essential for higher-level cognitive functions. How epigenetic dynamics participates in PFC development and aging is largely unknown. Here, we profiled epigenomic landscapes of rhesus monkey PFCs from prenatal to aging stages. The dynamics of chromatin states, including higher-order chromatin structure, chromatin interaction and histone modifications are coordinated to regulate stage-specific gene transcription, participating in distinct processes of neurodevelopment. Dramatic changes of epigenetic signals occur around the birth stage. Notably, genes involved in neuronal cell differentiation and layer specification are pre-configured by bivalent promoters. We identified a cis-regulatory module and the transcription factors (TFs) associated with basal radial glia development, which was associated with large brain size in primates. These TFs include GLI3, CREB5 and SOX9. Interestingly, the genes associated with the basal radial glia (bRG)-associated cis-element module, such as SRY and SOX9, are enriched in sex differentiation. Schizophrenia-associated single nucleotide polymorphisms are more enriched in super enhancers (SEs) than typical enhancers, suggesting that SEs play an important role in neural network wiring. A cis-regulatory element of DBN1 is identified, which is critical for neuronal cell proliferation and synaptic neuron differentiation. Notably, the loss of distal chromatin interaction and H3K27me3 signal are hallmarks of PFC aging, which are associated with abnormal expression of aging-related genes and transposon activation, respectively. Collectively, our findings shed light on epigenetic mechanisms underlying primate brain development and aging.

An ultrasensitive electrochemical method for rapid detection of mercury based on nanoporous gold capped with a novel Zr-MOF-SH/reduced graphene oxide aerogel composites.

In this work, an ultrasensitive electrochemical sensor based on Zr-MOF-SH/rGA/NPG was developed for the first time for the rapid determination of mercury ions. First, nanoporous gold (NPG) film was covered on the glassy carbon electrode (GCE) to offer a desirable substrate. Then, Zr-MOF-SH/rGA composites were dropped on the NPG film to form a modified electrode. Mercapto functionalized MOFs (Zr-MOF-SH) showed strong adsorption capability toward mercury ions, and the unique structure of reduced graphene oxide aerogel (rGA) provided various sites for coupling with Zr-MOF-SH as well as improved the electrochemical activity. As a consequence of the synergistic effect of Zr-MOF-SH, rGA, and NPG, the optimized Zr-MOF-SH/rGA/NPG/GCE sensor showed excellent detection performance toward mercury ions with a linear range from 0 to 200 nM and a low limit of detection of 1.4 nM. Meanwhile, the fabricated electrochemical sensor exhibited outstanding stability, reproducibility, and anti-interference ability. To verify the practical applicability, the Zr-MOF-SH/rGA/NPG/GCE was applied for the determination of mercury ions in real rice samples with desirable recovery rates ranging from 98.8% to 108.3%.

Soil application of graphitic carbon nitride nanosheets alleviate cadmium toxicity by altering subcellular distribution, chemical forms of cadmium and improving nitrogen availability in soybean (Glycine max L.).

Cadmium (Cd)-contamination impairs biological nitrogen fixation in legumes (BNF), threatening global food security. Innovative strategies to enhance BNF and improve plant resistance to Cd are therefore crucial. This study investigates the effects of graphitic carbon nitride nanosheets (g-C3N4 NSs) on soybean (Glycine max L.) in Cd contaminated soil, focusing on Cd distribution, chemical forms and nitrogen (N) fixation. Soybean plants were treated with 100 mg kg-1 g-C3N4 NSs, with or without 10 mg kg-1 Cd for 4 weeks. Soil addition of g-C3N4 NSs alleviated Cd toxicity and promote soybean growth via scavenging Cd-mediated oxidative stress and improving photosynthesis. Compared to Cd treatment, g-C3N4 NSs increased shoot and root dry weights under Cd toxicity by 49.5% and 63.4%, respectively. g-C3N4 NSs lowered Cd content by 35.7%-54.1%, redistributed Cd subcellularly by increasing its proportion in the cell wall and decreasing it in soluble fractions and organelles, and converted Cd from high-toxicity to low-toxicity forms. Additionally, g-C3N4 NSs improved the soil N cycle, stimulated nodulation, and increased the N-fixing capacity of nodules, thus increasing N content in shoots and roots by 12.4% and 43.2%, respectively. Mechanistic analysis revealed that g-C3N4 NSs mitigated Cd-induced loss of endogenous nitric oxide in nodules, restoring nodule development. This study highlights the potential of g-C3N4 NSs for remediating Cd-contaminated soil, reducing Cd accumulation, and enhancing plant growth and N fixation, offering new insights into the use of carbon nanomaterials for soil improvement and legume productivity under metal(loid)s stress.

CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation.

AIMS: As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance and malignant progression of gastric cancer (GC). METHODS: In vitro and in vivo models were conducted to investigate the manifestation and impact of CBX4 on cellular senescence and chemoresistance. High-throughput sequencing, chromatin immunoprecipitation, and co-immunoprecipitation techniques were utilized to identify the upstream regulators and downstream effectors associated with CBX4, revealing its intricate regulatory network. RESULTS: CBX4 diminishes the sensitivity of GC cells to cellular senescence, facilitating chemoresistance and GC development by deactivating the senescence-related Hippo pathway. Mechanistically, low-dose cisplatin transcriptionally downregulates CBX4 through CEBPB. In addition, CBX4 preserves the stability and cytoplasm-nuclear transport of YAP1, the key player of Hippo pathway, by inducing SUMO1 modification at K97 and K280, which competitively inhibits YAP1-S127 phosphorylation. CONCLUSIONS: Our study highlights the anti-senescence role of CBX4 and suggests that CBX4 inhibition in combination with low-dose cisplatin has the potential to overcome chemoresistance and effectively restrict GC progression.

[Application framework and model of Jingjin therapy in rehabilitation medicine].

The Jingjin therapy and rehabilitation medicine share commonalities and complement each other. The application of Jingjin therapy from a rehabilitation perspective can broaden the development path of traditional Chinese medicine (TCM) rehabilitation. This paper, based on relevant literature and research findings, elaborates on the connection between Jingjin syndrome differentiation acupuncture and rehabilitation assessment and treatment. It discusses the application framework of Jingjin's preventive treatment theory in disease prevention and rehabilitation, and forecasts the research model of Jingjin rehabilitation medicine from an integrative perspective of Chinese and western medicine. This study aims to improve the rehabilitation application thinking of Jingjin therapy and enrich the application methods and treatment approaches of TCM rehabilitation medicine.

Photocatalytic CO2 Reduction to Ethanol by ZnCo2O4/ZnO Janus Hollow Nanofibers.

Photocatalytic carbon dioxide (CO2) reduction for high-value hydrocarbon fuel production is a promising strategy to tackle global energy demand and climate change. However, this technology faces formidable challenges, primarily stemming from low yield and poor selectivity of C2 products of the desired hydrocarbon fuels. This study reported ZnO/ZnCo2O4 Janus hollow nanofibers (ZnO/ZCO JHNFs) prepared by electrospinning and atomic layer deposition. Photocatalytic tests revealed an ethanol yield of 4.99 µmol g-1 h-1 for ZnO/ZnCo2O4 JHNFs, surpassing mixed ZnO/ZnCo2O4 nanofibers (ZnO/ZCO NFs) by 4.35 times and pure ZnO by 12.7 times. The selectivity of 58.8% is 2.38 and 4.49 times higher than those of ZnO/ZnCo2O4 NFs and ZnO, respectively. These enhancements are attributed to efficient carrier separation facilitated by the ordered internal electric field of the Z-scheme heterojunction interface, validated by the energy band evaluations from experimentation and density functional theory (DFT) simulations and charge separation characterizations of photocurrent, impedance, and photoluminescence spectra. The Janus structure also effectively exposes the surface of ZnCo2O4 to CO2 molecules, increasing the active site availability, as confirmed by BET nitrogen adsorption/desorption, temperature-programmed desorption tests, and DFT adsorption energy calculations. This study proposes a novel approach for efficient photocatalytic hydrocarbon fuel production, with potential applications in energy and climate crisis mitigation.

Molecular mechanisms and clinical manifestations of hereditary hemorrhagic telangiectasia.

INTRODUCTION: Hereditary Hemorrhagic Telangiectasia (HHT) is charactered by telangiectasia and arteriovenous malformations (AVMs). Recurrent visceral and mucocutaneous bleeding is frequently reported among HHT patients, while data on the prevalence of thrombosis remains limited. This study aims to describe the clinical manifestations and molecular biological characteristics of HHT patients. METHODS: We conducted a retrospective study at Ruijin Hospital, affiliated with Shanghai Jiao Tong University School of Medicine. A total of 24 HHT patients, observed between January 2019 and December 2023, were included. We recorded the biological, clinical, and therapeutic events, with particular attention to bleeding and thrombotic events. Gene mutation analysis and blood constituent measurements were performed. RESULTS: The prevalence of bleeding among all HHT patients was 100 %, while thrombotic events were noted in 41.70 % of cases. Hepatic arteriovenous malformations (HAVMs) were identified in six patients, pulmonary arteriovenous malformations (PAVMs) in five patients, and cerebral arteriovenous malformations (CAVMs) in one patient. For patients with thrombosis, the discontinuation rates were 23.08 % for antiplatelet therapy and 33.33 % for anticoagulant therapy due to the increased risk of bleeding. Genetic mutations related to HHT were present in 16 patients, with ACVRL1 (activin A receptor-like type 1) mutations being the most frequent at 41.67 %, followed by ENG (endoglin) mutations at 20.83 %, and GDF2 (growth differentiation factor 2) mutations at 4.17 %. The incidence of PAVMs was 75.00 % in HHT1 patients with ENG mutations and 20 % in HHT2 patients with ACVRL1 mutations, while HAVMs occurred in 0 % and 40.00 % of these groups, respectively. Patients were divided into non-AVMs and AVMs groups. Compared to normal controls, von Willebrand factor (vWF) activity was significantly increased in all HHT patients (149.10 % vs. 90.65 %, P < 0.001). In the non-AVMs group, the median level of stromal cell-derived factor-1 (SDF-1) was significantly elevated (124.31 pg/mL vs. 2413.57 pg/mL, P < 0.05), while vWF antigen levels were markedly higher in the AVMs group (165.30 % vs. 130.60 %, P = 0.021). Further grouping of HHT patients based on bleeding and thrombosis phenotypes revealed that those with thrombosis had significantly higher median percentages of schistocytes (3.50 % vs. 0 %, P = 0.002), ferritin concentrations (318.50 µg/L vs. 115.50 µg/L, P = 0.001), and lactate dehydrogenase (LDH) levels (437 U/L vs. 105 U/L, P < 0.001). There were no significant differences in the activity of vWF, protein C (PC), protein S (PS), and factor VIII (FVIII) between the two groups. CONCLUSION: This study highlighted the complex relationship between arteriovenous malformations and genetic mutations in HHT patients. A comprehensive assessment of bleeding and thrombosis risks should be conducted for each HHT patient, additionally, further clinical studies are needed to explore the risk factors for thrombosis and anticoagulant-related bleeding in HHT.

Synthesis of N-Aryl-4-trifluoromethylthiazol-2-amines via Insertion/Annulation of Trifluoromethylimidoyl Sulfoxonium Ylides with Sodium Thiocyanate.

An efficient p-TsOH-mediated insertion of sodium thiocyanate into trifluoromethylimidoyl sulfoxonium ylides has been reported, affording annulated N-aryl-4-trifluoromethylthiazol-2-amines in 42-84% yields in a one-pot manner. This protocol encompasses a variety of trifluoromethylimidoyl sulfoxonium ylides with thiocyanate serving as the source of the "S-C═N" moiety of the thiazole ring. The versatile transformations of the resulting pharmacologically important N-aryl-4-trifluoromethylthiazol-2-amines were also demonstrated.

Active Targets and Potential Mechanisms of Erhuang Quzhi Formula in Treating NAFLD: Network Analysis and Experimental Assessment.

The purpose of this research was to investigate the main active components, potential targets of action, and pharmacological mechanisms of Erhuang Quzhi Formula (EHQZF) against NAFLD using network pharmacology, molecular docking, and experimental validation. The main active chemical components of EHQZF and the potential targets for treating NAFLD were extracted and analyzed. The PPI network diagram of "Traditional Chinese Medicine-Active Ingredients-Core Targets" was constructed and the GO, KEGG, and molecular docking analysis were carried out. Identification of components in traditional Chinese medicine compounds was conducted by LC-MS. NAFLD models were established and relevant pathologic indicators and Western blot were analyzed in vivo and ex vivo. Totally 8 herbs attributed to the liver meridian and 20 corresponding targets of NAFLD were obtained from EHQZF. Flavonoids and phenolic acids as the main components of EHQZF treated NAFLD through the MAPK/AKT signaling pathway. Pathway enrichment analysis focused on the MAPK/AKT signaling pathway and apoptosis signaling pathway. Molecular docking showed that Quercetin and Luteolin had stable binding structures with AKT1, STAT3, and other targets. Experiments showed that EHQZF reduced lipid accumulation, regulated changes in adipose tissue, inhibited the MAPK/AKT signaling pathway and exert multiple components, several targets, and multiple pathway interactions to treat NAFLD.

Path analysis of self-care amongst community-dwelling pre-ageing and older adults with chronic diseases: A salutogenic model.

With the trend towards ageing population globally, the salutogenic model can be integrated in interventions for pre-ageing and older adults to better support healthy ageing. However, there is limited research examining the salutogenic model's pathway amongst pre-ageing and older adults. Hence, this study aims to investigate pathways of the salutogenic model amongst pre-ageing and older adults with chronic diseases. Two hundred and eight pre-ageing and older adults were recruited from 11 Senior Activity Centres in Singapore. Data was collected using a self-reported questionnaire and analysed using path analyses. The indirect pathway from Subjective Cognitive Complaints to self-care abilities via sense of coherence and health practices were significant. Participants with higher sense of coherence may have increased capacities to execute more complex forms of self-care. Future interventions integrating the salutogenic model could enhance pre-ageing and older adults' self-care abilities to cope with chronic diseases and contribute to healthy ageing.

Efficacy of first-line chemotherapy based on primary site of tumor versus etoposide-platinum in advanced gastroenteropancreatic neuroendocrine carcinoma.

Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) constitute a rare and aggressive group of malignancies usually with widespread disease. There are limited studies on GEP-NECs, and therefore, we aim to acquire more information on the clinical features, treatment regimens, and prognosis. Methods: Data from advanced GEP-NECs patients who had not previously received systemic treatment for advanced disease at The First Affiliated Hospital of Nanjing Medical University from 2010 to 2022 were retrospectively collected. Relationships between clinical-pathological features, treatment regimens, and prognosis were investigated using Kaplan-Meier curves and cox regression models. Results: A total of fifty-four patients were enrolled in the study. The median age was 65.5 years and 79.6% were male. At diagnosis, 51.9% and 3.7% of patients developed liver and brain metastasis respectively. Sixteen (29.6%) patients received chemotherapy according to primary site of tumor (PST), while thirty-eight (70.4%) were treated with etoposide-platinum (EP) regimen, which based on the first-line treatment of advanced small cell lung cancer (SCLC). No significant differences on progression-free survival (PFS) and response rate were observed between these two groups. Univariate survival analysis showed that liver metastasis, elevated baseline serum carcinoembryonic antigen, elevated baseline serum neuron-specific enolase, elevated baseline serum lactate dehydrogenase, and elevated baseline serum neutrophil-to-lymphocyte ratio (NLR) were associated with shorter PFS. After multivariate analysis, elevated NLR was the only factor that remained significantly associated with shorter PFS (P=0.01). Conclusions: GEP-NECs are aggressive neoplasms, of which elevated NLR is proven to be an independent negative predictor. Treatment regimens based on PST are not inferior to regiments based on SCLC (EP) for GEP-NECs patients. Large-scale, prospective randomized controlled trials are required to establish the standard of care.

Clinical Implications of Acute Stent Mal-Apposition in the Left Main Coronary Artery.

Background: Intravascular ultrasound (IVUS) has been utilized to determine acute stent mal-apposition (ASM) after percutaneous coronary intervention (PCI) in the left main coronary artery (LMCA). However, the clinical consequences of this finding remain uncertain. This research aimed to evaluate the clinical implications of ASM in the LMCA using IVUS. Methods: In this study, 408 patients who underwent successful drug-eluting stent (DES) implantation in the LMCA were evaluated. We analyzed the prevalence and characteristics of ASM and its correlation with clinical outcomes. ASM is characterized by stent struts that are not in immediate proximity to the intimal surface of the vessel wall after initial stent deployment. Results: The observed incidence of LMCA-ASM post-successful PCI was 26.2%, both per patient and per lesion. Lesions with LMCA-ASM had a longer stent diameter, larger stent areas, and larger lumen areas compared to those without LMCA-ASM (4.0 ± 0.5 vs. 3.7 ± 0.4 mm, p < 0.001; 9.8 ± 2.0 vs. 9.0 ± 1.6 mm 2 , p < 0.001; 12.3 ± 1.9 vs. 10.1 ± 2.1 mm 2 , p < 0.001, respectively). The mean external elastic membrane (EEM) area (odds ratio (OR): 1.418 [95% confidence interval (CI): 1.295-1.556]; p < 0.001) emerged as an independent predictor of LMCA-ASM. During the observation period, LMCA-ASM did not display any association with device-oriented clinical endpoints (DoCE), which included cardiac death, target vessel-induced myocardial infarction (MI), stent thrombosis, and target lesion revascularization (TLR). Moreover, the DoCE incidence exhibited no significant disparity between patients with or without ASM (13.1 vs. 6.0%, p = 0.103). Conclusions: While LMCA-ASM was a not uncommon finding post-PCI, it did not correlate with adverse cardiac events in the present study.

Calcified Nodules in Non-Culprit Lesions with Acute Coronary Syndrome Patients.

Background: Calcified nodules (CN) have been linked to unfavorable clinical outcomes. However, there is a lack of systematic studies on non-culprit lesions with CN in patients with acute coronary syndromes (ACS). This study aims to investigate the frequency, distribution, predictors, and outcomes of CN in non-culprit lesions among ACS patients. Methods: We included 376 ACS patients who received successful stent placement in their culprit lesions. Intravascular ultrasound (IVUS) was performed to evaluate non-culprit lesions in left main arteries and all three coronary arteries (CA). CN was defined as accumulations of small nodular calcium deposits exhibiting a convex shape protruding into the lumen. Results: CNs was identified in 16.9% (121 of 712) per artery and 26.9% (101 of 376) per patient. They were predominantly located at the mid portion of the right coronary artery (26.3%) and the bifurcation site (59.9%). Patients with CN were older (63.57 ± 8.43 vs. 57.98 ± 7.15, p < 0.001) and had a higher prevalence of diabetes mellitus (55.4% vs. 42.2%, p = 0.022). However, there were no significant differences in baseline characteristics observed after propensity score matching (PSM). Multivariate analysis revealed that CN were independently associated with major adverse cardiovascular events (MACE) both before and after PSM (hazard ratio (HR): 0.341, 95% confidence interval (95% CI): 0.140-0.829, p = 0.018; HR: 0.275, 95% CI: 0.108-0.703, p = 0.007, respectively). During the observational period of 19.35 ± 10.59 months, the occurrence of MACE was significantly lower in patients with CN before and after PSM (5.9% vs. 16.7%, p = 0.046; 4.0% vs. 18.1%, p = 0.011; respectively). Conclusions: CN in non-culprit lesions with ACS patients was prevalent and caused fewer adverse clinical outcomes.

Volumetric Stent Expansion Index to Assess Tapering Lesions Using Intravascular Ultrasound and Its Clinical Outcomes.

Background: This study aimed to assess the clinical significance of generating a volumetric stent expansion index for tapering lesions through intravascular ultrasound (IVUS). Previous IVUS studies have used minimal stent area (MSA) to predict adverse outcomes. Methods: A total of 251 tapering lesions were treated in this study via IVUS guidance in 232 patients. Eight stent expansion indices were evaluated to determine the association of these indices with device-oriented clinical endpoints (DoCEs) after two-year follow-ups. These were the ILUMIEN III and IV standards, the ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions) standard, the IVUS-XPL (Impact of Intravascular Ultrasound Guidance on the Outcomes of Xience Prime Stents in Long Lesions) standard, the minimal volumetric expansion index (MVEI) using the Huo-Kassab or linear model, the MSA/vessel area at the MSA cross-section, the traditional stent expansion (MSA/mean proximal and distal reference lumen cross-sectional area), and MSA. Results: The MVEI was the only stent expansion index that correlated significantly with the two-year DoCEs (hazard ratio [HR], 1.91; 95% confidence interval [CI]: 1.16-3.96; p = 0.028). In the ROC analysis, the area under the curve for the MVEI was 0.71 (p = 0.002), with an optimal cut-off value of 62.2 for predicting the DoCEs. Conclusions: This is the first study to use IVUS for tapering lesions and demonstrate that the MVEI is an independent predictor of two-year DoCEs.

TCGA Database-Based Screening of Tumor Microenvironment Immunomodulators Related to Bladder Cancer Prognosis.

OBJECTIVE: Bladder cancer (BC), as the most common malignant tumor of the urinary tract, has a complex biological behavior. Currently, there are still some limitations in the diagnosis and treatment of BC. Despite the great progress made in immunotherapy, there is still a lack of key genes for the diagnosis of BC. Therefore, it is particularly important to explore the differentially expressed genes (DEGs) and their effectiveness on prognosis of BC with different tumor microenvironment scores. METHODS: The gene expression dataset of BC was downloaded from the Cancer Genome Atlas (TCGA) database. The correlation between clinicopathological characteristics of patients and scores of immune and stromal components was analyzed. Patients were divided into high and low score groups according to their tumor microenvironment score (Immune score, Stromal score, ESTIMATE score). DEGs between high and low score groups were identified using R software and then subjected to enrichment analyses to assess their potential biological functions and signaling pathways. The protein-protein interaction (PPI) network was constructed using the STRING database to further identify hub genes. The expression levels of hub genes in BC were verified by TCGA database. Subsequently, the hub genes were evaluated for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS), and corresponding forest plots were created. RESULTS: A total of 2346 DEGs were obtained, including 1120 up-regulated genes and 1226 down-regulated genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses found DEGs were mainly enriched in cell migration and immune-related pathways. Meanwhile, The PPI network finally yielded top 10 hub genes with predictive value, which included actin beta (ACTB), interleukin 6 (IL-6), Jun proto-oncogene (JUN), CD4 molecule (CD4), heat shock protein 90 alpha family class A member 1 (HSP90AA1), protein tyrosine phosphatase receptor type C (PTPRC), tumor protein p53 (TP53), SRC proto-oncogene (SRC), fibronectin 1 (FN1), and tumor necrosis factor (TNF). Among them, CD4, PTPRC, and SRC were potential protective factors for BC. CONCLUSION: The top 10 hub genes (ACTB, IL-6, JUN, CD4, HSP90AA1, PTPRC, TP53, SRC, FN1, TNF) obtained based on tumor microenvironment scores all had potential predictive value. Elevated expression of protective factors (CD4, PTPRC, and SRC) indicates better survival outcome of BC subjects. Further exploration of the molecular developmental mechanisms of these hub genes will help to develop novel personalized therapies and improve BC prognosis.