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Rationale: The phenomenon of hypercoagulability has not been previously documented in individuals with Morvan's syndrome, especially in those associated with contactin-associated protein-like receptor 2 (CASPR2)., Patient Concerns: A previously healthy 32-year-old Chinese male was admitted to the hospital with central and peripheral neurologic symptoms. The patient was tested positive for anti-CASPR2 antibodies, and also presented with an activated coagulation state on admission, characterized by a low activated partial thromboplastin time and a high platelet count. With gradual improvement of clinical symptoms, activated partial thromboplastin time, and platelet count returned to normal. Simultaneously, anti-CASPR2 antibody titers significantly decreased and eventually became undetectable., Diagnoses: The patient was diagnosed as Morvan's syndrome with positive anti-CASPAR2 antibodies accompanied with hypercoagulable state., Interventions: Plasmapheresis was administered to improve the symptoms combined with prednisolone acetate therapy., Outcomes: The patient experienced complete resolution of all symptoms during hospitalization and generally recovery after 2 months of discharge., Lessons: Emphasis should be directed towards hypercoagulability in individuals diagnosed with Morvan's syndrome, particularly those presenting with positive anti-CASPR2 antibodies. Anticoagulant therapy may represent a novel therapeutic approach for individuals afflicted with Morvan's syndrome and exhibiting positivity for anti-CASPR2 antibodies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Instantaneous wave-free ratio (iFR) is a new invasive indicator of myocardial ischaemia, and its diagnostic performance is as good as the "gold standard" of myocardial ischaemia diagnosis: fractional flow reserve (FFR). iFR can be approximated by iFR CT , which is calculated based on noninvasive coronary CT angiography (CTA) images and computational fluid dynamics (CFD). However, the existing methods for calculating iFR CT fail to accurately simulate the resting state of the coronary artery, resulting in low computational accuracy. Furthermore, the use of CFD technology limits its computational efficiency, making it difficult to meet clinical application needs. The role of coronary microcirculatory resistance compensation suggests that microcirculatory resistance can be adaptively reduced to compensate for increases in coronary stenotic resistance, thereby maintaining stable myocardial perfusion in the resting state. It is therefore necessary to consider this compensation mechanism to establish a high-fidelity microcirculation resistance model in the resting state in line with human physiology, and so to achieve accurate calculation of iFR CT ., Methods: In this study we successfully collected clinical data, such as FFR, in 205 stenotic vessels from 186 patients with coronary heart disease. A neural network model was established to predict coronary artery stenosis resistance. Based on the compensation mechanism of coronary microcirculation resistance, an iterative solution algorithm for microcirculation resistance in the resting state was developed. Combining the two methods, a simplified single-branch model combining coronary stenosis and microcirculation resistance was established, and the noninvasive and rapid numerical calculation of iFR CT was performed., Results: The results showed that the mean squared error (MSE) between the pressure drop predicted by the neural network value for the coronary artery stenosis model and the ground truth in the test set was 0.053 %, and correlation analysis proved that there was a good correlation between them (r = 0.99, p < 0.001). With reference to clinical diagnosis of myocardial ischaemia (using FFR as the gold standard), the diagnostic accuracy of the iFR CT calculation model for the 205 cases was 88.29 % (r = 0.71, p < 0.001), and the total calculation time was < 8 s., Conclusions: The results of this study demonstrate the utility of a simplified single-branch model in an iFR CT calculation method based on haemodynamics and deep learning, which is important for noninvasive and rapid diagnosis of myocardial ischaemia., Competing Interests: Declaration of competing interest We have not identified any conflict of interest to be disclosed regarding publication of this study., (Copyright © 2024. Published by Elsevier B.V.)

Background: Despite effective strategies, resistance in EGFR mutated lung cancer remains a challenge. Metabolic reprogramming is one of the main mechanisms of tumor drug resistance. A class of drugs known as "statins" inhibit lipid cholesterol metabolism and are widely used in patients with cardiovascular diseases. Previous studies have also documented its ability to improve the therapeutic impact in lung cancer patients who receive EGFR-TKI therapy. Therefore, the effect of statins on targeted drug resistance to lung cancer remains to be investigated., Methods: Prolonged exposure to gefitinib resulted in the emergence of a resistant lung cancer cell line (PC9GR) from the parental sensitive cell line (PC9), which exhibited a traditional EGFR mutation. The CCK-8 assay was employed to assess the impact of various concentrations of pitavastatin on cellular proliferation. RNA sequencing was conducted to detect differentially expressed genes and their correlated pathways. For the detection of protein expression, Western blot was performed. The antitumor activity of pitavastatin was evaluated in vivo via a xenograft mouse model., Results: PC9 gefitinib resistant strains were induced by low-dose maintenance. Cell culture and animal-related studies validated that the application of pitavastatin inhibited the proliferation of lung cancer cells, promoted cell apoptosis, and restrained the acquired resistance to EGFR-TKIs. KEGG pathway analysis showed that the hippo/YAP signaling pathway was activated in PC9GR cells relative to PC9 cells, and the YAP expression was inhibited by pitavastatin administration. With YAP RNA interference, pAKT, pBAD and BCL-2 expression was decreased, while BAX expression as increased. Accordingly, YAP down-regulated significantly increased apoptosis and decreased the survival rate of gefitinib-resistant lung cancer cells. After pAKT was increased by SC79, apoptosis of YAP down-regulated cells induced by gefitinib was decreased, and the cell survival rate was increased. Mechanistically, these effects of pitavastatin are associated with the YAP pathway, thereby inhibiting the downstream AKT/BAD-BCL-2 signaling pathway., Conclusion: Our study provides a molecular basis for the clinical application of the lipid-lowering drug pitavastatin enhances the susceptibility of lung cancer to EGFR-TKI drugs and alleviates drug resistance., (© 2024. The Author(s).)

We examine the causal effects of PM 2.5 exposure on the burden of long-term care (LTC) by matching a satellite-based PM 2.5 (particulate matter smaller than 2.5 micrometers (μm) in diameter) dataset with a nationally representative longitudinal study in China from 2011 to 2018. We find significant adverse effects of PM 2.5 exposure-instrumented by thermal inversions-on the LTC burden. A 10 μg/m 3 increase in annual PM 2.5 exposure increases average monthly hours of LTC and the associated financial costs by 28 h and CNY 452, respectively. The effects are greater for those who had never smoked nor experienced severe PM 2.5 pollution (annual average PM 2.5  > 35 μg/m 3 ) in the previous 5 years. We also find that as PM 2.5 increases, chronic diseases, particularly cardiovascular diseases, could lead to a higher likelihood of LTC dependency but reduce the total hours and costs of LTC provision. Finally, we find that PM 2.5 reduces the total years of LTC need, suggesting that PM 2.5 increases LTC costs by increasing the severity of LTC dependency, rather than the duration of LTC need. Our findings can assist policymakers in planning for LTC provisions and clean air policies., (© 2024 John Wiley & Sons Ltd.)

To assess the anatomy of the inferior mesenteric artery (IMA) and its branches by reviewing laparoscopic left-sided colorectal cancer surgery videos and comparing them with preoperative three-dimensional computed tomography (3D-CT) angiography, to verify the accuracy of 3D-CT vascular reconstruction techniques. High-definition surgical videos and preoperative imaging data of 200 patients who underwent laparoscopic left-sided colorectal cancer surgery were analysed, and the alignment of the IMA and its branches in relation to the inferior mesenteric vein (IMV) was observed and summarized. The above two methods were used to measure the length of the IMA and its branches. Of 200 patients, 47.0% had the sigmoid arteries (SAs) arise from the common trunk with the superior rectal artery (SRA), and 30.5% had the SAs arise from the common trunk with the left colic artery (LCA). In 3.5% of patients, the SAs arising from both the LCA and SRA. The LCA, SA, and SRA emanated from the same point in 13.5% of patients, and the LCA was absent in 5.5% of patients. The range of D cm (IMA length measured by intraoperative silk thread) and d cm (IMA length measured by 3D-CT vascular reconstruction) in all cases was 1.84-6.62 cm and 1.85-6.52 cm, respectively, and there was a significant difference between them. (p < 0.001). The lengths between the intersection of the LCA and IMV measured intraoperatively were 0.64-4.29 cm, 0.87-4.35 cm, 1.32-4.28 cm and 1.65-3.69 cm in types 1A, 1B, 1C, and 2, respectively, and there was no significant difference between the groups (p = 0.994). There was only a significant difference in the length of the IMA between the 3D-CT vascular reconstruction and intraoperative observation data, which can provide guidance to surgeons in preoperative preparation., (© 2024. The Author(s).)

Background: Inflammation is a part of tumours, and inflammatory cells can affect the proliferation, invasion, and development of tumour cells. An increasing number of peripheral blood inflammatory markers have been found to play very important roles in the treatment and prognosis of cancer patients. The systemic inflammatory response index (SIRI) is a newer inflammatory marker, and its role in colorectal cancer, especially in locally advanced rectal cancer, is still unclear., Methods: From 2015 to 2020, 198 patients with locally advanced rectal cancer (LARC) who underwent surgery following neoadjuvant chemoradiotherapy (Neo-CRT) were analysed. Patients were categorized into good- and poor- response groups according to their pathological results, and clinical characteristics and baseline parameters were compared between the two groups. The optimal cutoff values for inflammatory indicators were determined using receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using the Cox proportional hazard model. Survival analysis was performed via the Kaplan‒Meier method., Results: After patients were grouped into good and poor response groups, indicator differences were found in CEA, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and SIRI. According to the ROC analysis, the NLR (P = 0.015), SII (P = 0.001), and SIRI (P = 0.029) were significant prognostic factors. After univariate and multivariate analyses of the Cox proportional hazards regression model, only the SIRI was found to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Finally, Kaplan‒Meier survival curves also confirmed the ability of the SIRI to predict survival., Conclusion: The preoperative SIRI can be used to predict the response to Neo-CRT in LARC patients and is an independent predictor of OS and DFS in postoperative patients. A high SIRI was associated with poor radiotherapy response and predicted poor OS and DFS., (© 2024. The Author(s).)

A photonic distributed compressive sampling (PDCS) approach for identifying the spectra of multi-node wideband sparse signals is proposed. The scheme utilizes wavelength division multiplexing (WDM) technology to transmit multi-node signals to a central station, where distributed compressive sampling (DCS) based on the random demodulator (RD) model is employed to simultaneously identify the signal spectrum. By exploiting signal correlations among nodes, DCS achieves a higher compression ratio of the sampling rate than single-node compressive sampling (CS). In a semi-physical simulation experiment, we demonstrate the feasibility of the approach by recovering the spectra of two wideband sparse signals from nodes located 20 km and 10 km away. The spectra of two signals with a mixed support-set sparsity of 2 and 4 are recovered with a compression ratio of 8 and 4, respectively. We further investigate the impact of common parts and the number of nodes on PDCS performance through numerical simulation. The proposed system takes advantage of the ultra-high bandwidth of photonic technology and the low loss of optical fiber transmission, making it suitable for long-distance, multi-node, and large-coverage electromagnetic spectrum identification.

Nitrogen complexation with π-conjugated ligands is an effective strategy for synthesizing luminescent molecules. The asymmetric bridging ligands L (L1 and L2) have been designed. The terminal chelating sites of the L1 and L2 bridging ligands consisted of 2,2'-bipyridine (bpy) and 1,10-phenanthroline moieties (where L = L1 and L2; L1 = 2-(3-((4-([2,2'-bipyridin]-6-yl)benzyl)oxy)phenyl)-1 H -imidazo[4,5- f ][1,10]phenanthroline and L2 = 2-(3-((4-(6-phenyl-[2,2'-bipyridin]-4-yl)benzyl)oxy)phenyl)-1 H -imidazo[4,5- f ][1,10]phenanthroline). The full use of the synthetic strategy of the "complexes as ligands and complexes as metals" was expected to successfully design and synthesize a series of conjugated metal-exchange complexes linked by the asymmetric bridging ligands L1 and L2. These compounds included monometallic complexes Ru(L) and (L)Ru (C1, C2, C7, and C8), homometallic complexes Ru(L)Ru (C3 and C4), and heterometallic complexes Os(L)Ru and Ru(L)Os (C5, C6, C9, and C10) with Ru- or Os-based units. C3-C10 complexes exhibited various degrees of octahedral distortion around the Ru(II) or Os(II) center, which was consistent with the optimized geometry of the coordination complexes based on density functional theory calculation. These complexes exhibited intense spin-allowed ligand-centered transitions with high absorbance at around 288 nm upon absorbing visible light. Notably, all complexes exhibited spin-allowed metal-to-ligand charge transfer absorption of the Ru-based units in the 440-450 nm range. In addition, the heterometallic C5, C6, C9, and C10 complexes showed absorption of the Os-based units in the range of 565-583 nm. The intramolecular energy transfer of C3 and C5 was briefly discussed by comparing the emission intensity of monometallic C1 and C2 to that of binuclear complexes C3 and C5, respectively. The results indicated that the intramolecular energy transfer of the Ru(II)/Os(II) polypyridine complexes proceeded from the Ru(II)- to the Os(II)-based units in the heterometallic C5 and C6 complexes.

Background and Purpose: Low-grade inflammation, a common feature of both diabetes and periodontitis, partly accounts for the complexity and refractoriness of diabetes-associated periodontitis. Adiponectin (APN), the most abundant adipokine in human blood, has been widely reported to have anti-inflammatory functions. Herein, we investigated the ability of an APN receptor agonist, AdipoAI, to alleviate diabetes-associated periodontitis. Furthermore, we revealed the possible mechanism underlying its anti-inflammatory effects., Experimental Approach: The maxillary first molar of Zucker diabetic fatty (ZDF) rats was ligated to construct a diabetes-associated periodontitis model, and rats were administered AdipoAI by gavage. We examined diabetes-related indexes, pathological changes in insulin target organs, alveolar bone resorption and systemic and local inflammation. In vitro, transwell assays were used to evaluate monocyte/macrophage migration induced by human gingival fibroblasts (hGFs) with/without AdipoAI treatment. Additionally, we examined chemokine expression levels in hGFs and hGF-induced monocyte/macrophage migration upon siRNA knockdown of Adiponectin receptor expression. Expression of Adipo1/Adipo2 receptors and inflammation-related signalling pathways were examined by IHC and WB, followed by confirmation with an NF-κB P65 inhibitor (BAY 11-7082)., Key Results: AdipoAI lowered fasting blood glucose and serum insulin in ZDF rats and alleviated inflammation in insulin target tissues. Locally, AdipoAI reduced alveolar bone absorption and gingival inflammation. Mechanistically, AdipoAI inhibited hGF-induced monocyte/macrophage migration by reducing CCL2 secretion. In hGFs, AdipoAI attenuated LPS-induced activation of NF-κB P65 and CCL2 expression, which was dependent on the Adipo receptor 1., Conclusion and Implications: AdipoAI, with its ability to alleviate inflammatory damage in tissues, is a candidate for diabetes-associated periodontitis treatment., (© 2023 British Pharmacological Society.)

Photonic compressive sampling (PCS) is an effective method to recover wideband sparse radio frequency (RF) signals. However, the noisy and high-loss photonic link leads to signal-to-noise ratio (SNR) degradation of the RF signal to be tested, which limits the recovery performance of the PCS system. In this paper, a random demodulator-based PCS system with 1-bit quantization is proposed. The system consists of a photonic mixer, a low-pass filter, a 1-bit analog-to-digital converter (ADC), and a digital signal processor (DSP). The 1-bit quantized result is used to recover the spectra of the wideband sparse RF signal with the binary iterative hard thresholding (BIHT) algorithm, which can alleviate the negative impact of the SNR degradation caused by the photonic link. A full theoretical framework of the PCS system with 1-bit quantization is given. Simulation results show that the PCS system with 1-bit quantization can provide better recovery performance than the traditional PCS system under low SNR and stringent bit budget.

Background: The role of ferroptosis in irreversible pulpitis (IP) remains unclear. The competing endogenous RNA (ceRNA) theory that has been widely investigated is rarely used studied in IP. Hub lncRNAs selected from a ceRNA network may provide a novel hypothesis for the interaction of ferroptosis and IP., Methods: Differentially expressed genes (DEGs) were intersected with 484 ferroptosis markers to identify differentially expressed ferroptosis-related genes (DE-FRGs). Functional analysis and protein-protein interaction (PPI) networks were constructed to reveal the functions of DE-FRGs. Then, coexpression analyses were conducted between DE-FRGs and DElncRNAs to define ferroptosis-related DElncRNAs (FR-DElncRNAs). Predictions of DE-FRG- and FR-DElncRNA-related miRNAs were obtained, and members of both groups were selected. Additionally, two ceRNA networks consisting of FR-DElncRNAs, miRNAs and DE-FRGs from upregulated and downregulated groups were built. Finally, the hub lncRNAs of the ceRNA networks were used for immuno-infiltration analysis and qPCR verification., Results: According to the results of PCA and clustering analysis, 5 inflamed and 5 healthy pulp tissue samples were selected for analysis. The intersection of DEGs with 484 ferroptosis marker genes identified 72 DE-FRGs. The response to stimulus, cellular process, signaling, localization, and biological regulation pathways related to DE-FRGs were enriched. In total, 161 downregulated and 40 upregulated FR-DElncRNAs were chosen by coexpression analysis for further investigation. The MultimiR package and starBase were used to predict miRNAs of DE-FRGs and FR-DElncRNAs, respectively. The upregulated ceRNA network contained 2 FR-DElncRNAs (↑), 19 miRNAs (↓) and 22 DE-FRGs (↑). The downregulated network contained 44 FR-DElncRNAs (↓), 251 miRNAs (↑) and 10 DE-FRGs (↓). Six hub lncRNAs were identified based on the MCC method (LUCAT1 and AC106897.1 ↑; LINC00943, AL583810.1, AC068888.1, and AC125257.1↓). In addition, strong relationships between hub lncRNAs and immune cells were shown by immune infiltration analysis. Finally, validated by qPCR assays of the pulp tissue of IP patients, the expression levels in clinical samples were consistent with the microarray data., Conclusion: Two ceRNA networks were comprehensively constructed, and 6 hub lncRNAs were identified. These genes provide novel insights into the relationship between ferroptosis and IP. Intriguingly, the LINC00943/hsa-miR-29a-3p/PDK4 axis was deemed to be the key node in this network., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xie, Yu, Liu, Zhou, Fang, Qiu and Wu.)

Non-infectious chronic diseases, especially inflammatory bowel diseases (IBDs), hypertension, and diabetes mellitus, are characterized by a prolonged and multisystemic course, and their incidence increases annually, usually causing serious economic burden and psychological stress for patients. Therefore, these diseases deserve scientific and consistent disease management. In addition, the lack of a comprehensive "early disease clues tracking-personalized treatment system-follow-up" model in hospitals also exacerbates this dilemma. Based on these facts, we propose an individualized prediction management system for IBDs based on chronic diseases, focusing on the established IBDs-related prediction models and summarizing their advantages and disadvantages. We call on researchers to pay attention to the integration of models with clinical practice and the continuous correction of models to achieve truly individualized medical treatment for chronic diseases, thus providing substantial value for the rapid diagnosis and adequate treatment of chronic diseases such as IBDs, which follow the "relapse-remission" disease model, and realizing long-term drug use and precise disease management for patients. The goal is to achieve a new level of chronic disease management by scientifically improving long-term medication, precise disease management, and individualized medical treatment, effectively prolonging the remission period and reducing morbidity and disability rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Cai, Cao, Liu, Zhang, Liu, Jiang, Chen, Fu, Xia and Yi.)

Objective: Epilepsy is associated with an increased risk of cardiovascular disease and mortality. Whether cardiac structure and function are altered in epilepsy remains unclear. To address this, we conducted a systematic review and meta-analysis of studies evaluating cardiac structure and function in patients with epilepsy., Methods: We searched the electronic databases MEDLINE, PubMed, COCHRANE, and Web of Science from inception to 31 December 2021. Primary outcomes of interest included left ventricular ejection fraction (LVEF) for studies reporting echocardiogram findings and cardiac weight and fibrosis for postmortem investigations. Study quality was assessed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tools., Results: Among the 10 case-control studies with epilepsy patients (n = 515) and healthy controls (n = 445), LVEF was significantly decreased in epilepsy group compared with controls (MD: -1.80; 95% confidence interval [CI]: -3.56 to -0.04; P = 0.045), whereas A-wave velocity (MD: 4.73; 95% CI: 1.87-7.60; P = 0.001), E/e' ratio (MD: 0.39; 95% CI: 0.06-0.71; P = 0.019), and isovolumic relaxation time (MD: 10.18; 95% CI: 2.05-18.32; P = 0.014) were increased in epilepsy, compared with controls. A pooled analysis was performed in sudden unexpected death in epilepsy (SUDEP) cases with autopsy data (n = 714). Among SUDEP cases, the prevalence of cardiac hypertrophy was 16% (95% CI: 9%-23%); cardiac fibrosis was 20% (95% CI: 15%-26%). We found no marked differences in cardiac hypertrophy, heart weight, or cardiac fibrosis between SUDEP cases and epilepsy controls., Significance: Our findings suggest that epilepsy is associated with altered diastolic and systolic echocardiogram parameters compared with healthy controls. Notably, SUDEP does not appear to be associated with a higher incidence of structural cardiac abnormalities, compared with non-SUDEP epilepsy controls. Longitudinal studies are needed to understand the prognostic significance of such changes. Echocardiography may be a useful noninvasive diagnostic test in epilepsy population., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Aim: The authors conducted a meta-analysis to determine the association between time-to-surgery (TTS) after neoadjuvant chemotherapy and patient outcomes in locally advanced gastric cancer. Methods: Electronic databases were searched to identify potential studies, in which the authors compared patient outcomes between those with TTS within 4 (and 6) weeks of completion of neoadjuvant chemotherapy and those after 4 (and 6) weeks. Results: Six studies, including 1238 patients, were eligible for inclusion. Pooled data showed no significant differences in rates of pathological complete response, major pathological response, ypN0, complications, R0 resection and operative time between groups of longer TTS and shorter TTS. Conclusion: There was no statistically advantageous impact of prolonged TTS on pathological and surgical outcomes. Large, population-based studies are warranted.

Novel monometallic (μ-LL')Ru, Ru(μ-LL'), homobimetallic Ru(μ-LL')Ru, and heterodimetallic Ru(μ-LL')Os and Os(μ-LL')Ru complexes based on two asymmetrical ligands LL' (where LL' = L 1 L 1' , L 2 L 2' ) have been synthesized and characterized. Spectroscopic analysis indicates that all complexes exhibit intense spin-allowed ligand-centered (LC) transitions at 288 nm and Ru-based moderate spin-allowed MLCT absorption between 440-450 nm. The Ru(μ-LL')Os and Os(μ-LL')Ru dinuclear complexes show Os-based unit absorption in the range of 565-583 nm. The Ru-based units of the complexes present different emission intensities due to differing steric hindrance at the coordination sites of the two bridging ligands. The Os(μ-LL')Ru dinuclear complexes present weaker emission intensity than their parent monometallic complexes (μ-LL')Ru. These results indicate that the emission of Os(μ-LL')Ru dinuclear complexes is quenched by the Os(II)-based units.

Background: Extramammary Paget's disease (EMPD) is a rare malignant cutaneous tumour that is commonly located in anogenital regions. The diagnosis of the disease is always delayed, and treatment is usually troublesome. This study aims to summarise the clinicopathological characteristics and the risk factors of prognosis for EMPD in anogenital regions, potentially providing evidence for the diagnosis and treatment of anogenital EMPD., Methods: 688 patients were sourced from the Surveillance, Epidemiology and End Results (SEER) program between 1992 and 2021. In total, 176 participants from our centre from between 2011 and 2021 were included to investigate the characteristics and prognosis for EMPD in anogenital regions., Results: From the SEER program data, patient age of 65 years or older, metastasis of lymph nodes, Spanish-Hispanic-Latino race, diameter exceeding 10cm and lesions located anally were revealed as independent risk factors for shorter cancer-specific survival (CSS). However, the data from our centre highlighted that metastasis of lymph nodes and tumours extending through the epidermis are independent risk factors of shortened progression-free survival (PFS) and CSS of anogenital EMPD., Conclusion: This synthesised study revealed that some characteristics are regarded as risk factors for poor clinical prognosis, which have potential value in formulating more normative and effective strategies for patients with EMPD in anogenital regions.

Background: Adiponectin (APN) is an endogenous adipokine secreted from adipocytes that exerts anti-inflammatory properties. AdipoAI is an orally active adiponectin receptor agonist identified by our group that can emulate APN's anti-inflammatory properties through mechanisms that are not fully understood. LncRNAs, a type of noncoding RNA more than 200 bp in length, have been demonstrated to have abundant biological functions, including in anti-inflammatory responses., Materials and Result: In the current study, we performed a lncRNA microarray in LPS-induced Raw264.7 cells that were prestimulated with AdipoAI and screened 110 DElncRNAs and 190 DEmRNAs. Enrichment analyses were conducted on total mRNAs and DEmRNAs, including GSVA, ssGSEA, GO/KEGG, GSEA, and PPI analysis. Among all these processes, endocytosis was significantly enriched. A coexpression analysis was built based on DElncRNAs and DEmRNAs. Then, using TargetScan and miRwalk to predict related microRNAs of DElncRNAs and DEmRNAs, respectively, we established competing endogenous RNA (ceRNA) networks including 54 mRNAs from 8 GO items. Furthermore, 33 m6A methylation-related marker genes were obtained from a previous study and used for the construction of an m6A-related lncRNA network by coexpression analysis. We identified FTO as the hub gene of the network and 14 lncRNAs that interacted with it. The expression levels of 10 lncRNAs selected from ceRNA and FTO-related lncRNA networks were validated with qRT‒PCR. Finally, macrophage phenotype scores showed that AdipoAI could attenuate the M2b and M2c polarization of macrophages and correlate with the above lncRNAs., Conclusion: Our work reveals that lncRNAs might be involved in the anti-inflammation process of AdipoAI in LPS-induced macrophages through the ceRNA network and the epigenetic regulation of m6A. Mechanistically, these lncRNAs associated with AdipoAI might be related to endocytosis and polarization in macrophages and provide new candidates for the anti-inflammatory application of APN and its receptor agonist., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Wu, Xie, Liu, Chen, Tu, Chen, Fang and Qiu.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Purpose: Reassessment tools of response to long-course neoadjuvant chemoradiation treatment (nCRT) in patients with locally advanced rectal cancer (LARC) are important in predicting complete response (CR) and thus deciding whether a wait-and-watch strategy can be implemented in these patients. Choosing which routine reassessment tools are optimal and when to use them is still unclear and will be researched in the study., Methods: Altogether, 250 patients with LARC who received nCRT from 2013 to 2021 and were followed up were retrospectively reviewed. Common reassessment tools of response included digital rectal examination (DRE), clinical examination and symptoms, endoscopy, biopsy, magnetic resonance imaging (MRI), and blood biomarkers., Results: Overall, 27.20% (68/250) patients had a complete response and 72.80% (182/250) did not. The combination of MRI, endoscopy, and biopsy showed the best performance in terms of accuracy of 74% and area under the curve (AUC, 0.714, 95% CI 0.546-0.882). Reassessing through DRE and presence of symptoms failed to improve the efficacy of response reassessment. After 100 days, biopsy as an assessment tool would obtain a substantial rise in accuracy from 51.28 to 100% (p = 0.003)., Conclusion: The combination of MRI, endoscopy, and biopsy is suitable as the reassessment tool of response for applying a wait-and-watch strategy after long-course nCRT in patients with LARC. The accuracy of biopsy as reassessment tools would be improved if they were used over 100 days after nCRT in patients with rectal cancer., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Stomach adenocarcinoma (STAD) is a highly heterogeneous disease and is among the leading causes of cancer-related death worldwide. At present, TNM stage remains the most effective prognostic factor for STAD. Exploring the changes in gene expression levels associated with TNM stage development may help oncologists to better understand the commonalities in the progression of STAD and may provide a new way of identifying early-stage STAD so that optimal treatment approaches can be provided., Methods: The RNA profile retrieving strategy was utilized and RNA expression profiling was performed using two large STAD microarray databases (GSE62254, n = 300; GSE15459, n = 192) from the Gene Expression Omnibus (GEO) and the RNA-seq database within the Cancer Genome Atlas (TCGA, n = 375). All sample expression information was obtained from STAD tissues after radical resection. After excluding data with insufficient staging information and lymph node number, samples were grouped into earlier-stage and later-stage. Samples in GSE62254 were randomly divided into a training group (n = 172) and a validation group (n = 86). Differentially expressed genes (DEGs) were selected based on the expression of mRNAs in the training group and the TCGA group (n = 156), and hub genes were further screened by least absolute shrinkage and selection operator (LASSO) logistic regression. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the hub genes in distinguishing STAD stage in the validation group and the GSE15459 dataset. Univariate and multivariate Cox regressions were performed sequentially., Results: 22 DEGs were commonly upregulated (n = 19) or downregulated (n = 3) in the training and TCGA datasets. Nine genes, including MYOCD, GHRL, SCRG1, TYRP1, LYPD6B, THBS4, TNFRSF17, SERPINB2, and NEBL were identified as hub genes by LASSO-logistic regression. The model achieved discrimination in the validation group (AUC = 0.704), training-validation group (AUC = 0.743), and GSE15459 dataset (AUC = 0.658), respectively. Gene Set Enrichment Analysis (GSEA) was used to identify the potential stage-development pathways, including the PI3K-Akt and Calcium signaling pathways. Univariate Cox regression indicated that the nine-gene score was a significant risk factor for overall survival (HR = 1.28, 95% CI 1.08-1.50, P = 0.003). In the multivariate Cox regression, only SCRG1 was an independent prognostic predictor of overall survival after backward stepwise elimination (HR = 1.21, 95% CI 1.11-1.32, P < 0.001)., Conclusion: Through a series of bioinformatics and validation processes, a nine-gene signature that can distinguish STAD stage was identified. This gene signature has potential clinical application and may provide a novel approach to understanding the progression of STAD., (© 2022. The Author(s).)

Purpose: To investigate the clinical value of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF- α ), and interferon- γ (IFN- γ ) in diagnosis and severity assessment of lung cancer., Methods: In this observational study, 50 physical examination healthy subjects were included in the control group and 100 lung cancer patients were included in the study group. In the study group, 53 cases with pleural effusion were subgrouped to the pleural effusion group ( n  = 53), while 47 patients were assigned to the nonpleural effusion group ( n  = 47). Plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF- α , IFN- γ , and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of all eligible subjects were collected and compared., Results: The study group showed significantly higher levels of plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF- α , and IFN- γ versus healthy subjects ( P < 0.05). Deterioration of lung cancer was associated with increased plasma cytokine levels and APACHE II scores. The combination assay of the above plasma cytokines showed significantly better diagnostic efficacy for lung cancer versus the single assay of the cytokines. Dead patients had higher plasma cytokine levels versus survived patients. The accuracy of plasma IL-2, IL-4, IL-6, IL-10, TNF- α , and IFN- γ levels in the severity assessment of lung cancer was comparable with that of the APACHE II scale., Conclusion: The plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF- α , and IFN- γ are effective markers for the diagnosis of lung cancer. The combined assay contributes to the early diagnosis of lung cancer patients, and the persistent elevation of cytokines suggests an increased risk of death in lung cancer patients, so the detection of cytokine levels facilitates the severity assessment of lung cancer., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jin Ma et al.)

Background: Peritoneal carcinomatosis (PC) of gastric cancer indicates a poor outcome and is mainly diagnosed by staging laparoscopy (SL). This study was designed to develop a risk stratification model based on the number of risk factors to exempt low-risk patients from unnecessary SL., Methods: This was a retrospective cohort study based on a single institution between January 2015 and December 2019. SL is indicated for patients of advanced locoregional stage, and clinicopathologic characteristics of 535 consecutive patients were included. PC-associated variables were identified by logistic regression analysis. A risk stratification model based on the number of risk factors was constructed, and we defined its predictive value with a receiver operating characteristic (ROC) curve and negative predictive value., Results: In total, 15.9% of included patients were found to have PC during SL. Borrmann type IV, elevated CA125, and tumour diameter ≥5 cm were independent risk factors of PC. These three factors combined with cT4 were selected as predictive factors, and the number of predictive variables was significantly related to the possibility of PC (2.0%, 12.8%, 20.0%, 54.2%, and 100%, respectively). When the cutoff value is more than one predictive factor, the negative predictive value is 98.0%, with an area under the curve of 0.780. This model could exempt 29.8% of unnecessary SL compared to the indication of the current NCCN guideline., Conclusions: We constructed a simple model to predict the probability of PC using the number of predictive factors. It is recommended that patients without any of these factors should be exempt from SL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Li, Guan, Liu, Li, Ying, Shan and Li.)

Objective: To analyze the impact of expression of miR-504-3p on the proliferation, migration, cell cycle transit and rate of apoptosis of NSCLC cells and explore the underlying mechanisms. Methods: The Cancer Genome Atlas (TCGA) database was used to compare the expression levels of miR-504 between NSCLC tissues and normal lung tissues. NSCLC cells were transfected with lentiviral vectors that either overexpressed or knocked down miR-504-3p to evaluate its effects on NSCLC biological behavior. Quantitative Real Time Polymerase Chain Reaction was used to measure the levels of miR-504-3p and Interferon-Induced Transmembrane Protein 1 ( IFITM1 ). A luciferase reporter array was used to reveal whether miR-504-3p directly targets IFITM1 . Results: The expression of miR-504 was significantly down-regulated in lung cancer tissues compared to normal lung tissues. Overexpression of miR-504-3p in NSCLC cell lines inhibited cell proliferation, migration and promoted cell apoptosis. Meanwhile, changes in the expression level of miR-504-3p had no significant effect on NSCLC cell cycle progression. Moreover, over-expressed miR-504-3p following its transfection significantly decreased the expression of IFITM1 in NSCLC cell lines and suppressed the activity of the luciferase reporter containing wild type but not mutant IFITM1 3' -UTR. Conclusion: miR-504-3p inhibits cell proliferation and migration and promotes cell apoptosis in NSCLC cells. MiR-504-3p decreases IFITM1 expression in NSCLC cells, which may be a potential mechanism of its tumor-suppressive functions in NSCLC.

Background and Objectives: Epilepsy is associated with an increased risk of cardiovascular disease and premature mortality, including sudden unexpected death in epilepsy (SUDEP). Serious cardiac arrythmias might go undetected in routine epilepsy and cardiac investigations., Methods: This prospective cohort study aimed to detect cardiac arrhythmias in patients with chronic drug-resistant epilepsy (≥5 years duration) using subcutaneous cardiac monitors for a minimum follow-up duration of 12 months. Participants with known cardiovascular disease or those with abnormal 12-lead ECGs were excluded. The device was programmed to automatically record episodes of tachycardia ≥140 beats per minute (bpm), bradycardia ≤40 bpm for ≥3 seconds, or asystole ≥3 seconds., Findings: Thirty-one patients underwent subcutaneous cardiac monitoring for a median recording duration of 2.2 years (range 0.5-4.2). During this time, 28 patients (90.3%) had episodes of sustained (≥30 seconds) sinus tachycardia, 8/31 (25.8%) had sinus bradycardia, and 3 (9.7%) had asystole. Three patients (9.7%) had serious cardiac arrhythmias requiring additional cardiac interventions. Among them, 2 patients had prolonged sinus arrest and ventricular asystole (>6 seconds), leading to pacemaker insertion in one, and another patient with epileptic encephalopathy had multiple episodes of recurrent nonsustained polymorphic ventricular tachycardia and bundle branch conduction abnormalities. The time to first detection of a clinically significant cardiac arrhythmia ranged between 1.2 and 26.9 months following cardiac monitor insertion., Discussion: Implantable cardiac monitors detected a high incidence of clinically significant cardiac arrhythmias in patients with chronic drug-resistant epilepsy, which may contribute to the incidence of premature mortality, including SUDEP., (© 2022 American Academy of Neurology.)

Backgrounds: Perioperative chemotherapy (PEC) and neoadjuvant chemotherapy (NAC) have become a vital part of locally advanced gastric cancer (LAGC) treatment, but the optimal duration of PEC has not been studied. The aim of this study was to demonstrate the possibility of duration reduction in PEC in the adjuvant chemotherapy (AC) phase for ypN0 patients., Methods: We included LAGC patients who achieved ypN0 after NAC in our institution from 2005 to 2018. The risk/benefit of AC and other covariates were majorly measured by overall survival (OS) and progression-free survival (PFS). We developed a survival-tree-based model to determine the optimal PEC duration for ypN0 patients in different classes., Results: A total of 267 R0 resection patients were included. There were 55 patients who did not receive AC. The 5-year OS was 74.34% in the non-AC group and 83.64% in the AC group with a significant difference (p = 0.012). Multivariate Cox regression revealed that both AC (AC vs. non-AC: HR, 0.49; 95%CI, 0.27-0.88; p = 0.018) and ypT stages (ypT3-4 vs. ypT0-2: HR, 2.00; 95%CI, 1.11-3.59; p = 0.021) were significant protective/risk factors on patients OS and PFS. A decision tree model for OS indicated an optimal four to six cycles of PEC, which was recommended for ypT0-2N0 patients, while a minimum of five PEC cycles was recommended for ypT3-4N0 patients., Conclusion: AC treatment is still necessary for ypN0. The duration reduction could be applied for the ypT0-2N0 stage patients but may not be suitable for higher ypT stages and beyond. A multicenter-based study is required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Wang, Shan, Ying, Zhang, Li, Jia, Miao, Xue, Li, Li and Ji.)

Background: Regarding the overlap anastomosis and recently introduced π-shaped anastomosis, there is no consensus on which intracorporeal esophagojejunostomy (EJS) methods are preferred using linear stapler in totally laparoscopic total gastrectomy (TLTG). This study aims to evaluate the short-term outcomes using two methods., Methods: Patients with upper gastric cancer underwent TLTG with either π-shaped (n = 48) or the modified overlap method using knotless barbed sutures (MOBS) (n = 37) were included in our study. Intraoperative and perioperative outcomes were compared., Results: All patients achieved R0 resection margin. The overall esophagojejunal (E-J)-related complications rate was 7.06%. There was no significant difference between the two groups in terms of postoperative complications, margin distance, numbers of lymph nodes (LNs), length of stay. In the π-shaped group, anastomosis time (19.61 ± 7.17 min vs. 27.09 ± 3.59 min, p < 0.001) was significantly lower. The consumable costs for surgery were similar (44 507.74¥ [42 933.03-46 937.29] vs. 43 718.36¥ [42 743.25-47 256.06], p = 0.825). The first defection time was significantly longer in π-shaped group (131.00 h [93.75-171.25] vs. 100.00 h [85.00-120.00], p = 0.026), whereas the other postoperative recovery parameters were similar. No mortality was observed., Conclusions: Both methods showed similar short-term postoperative outcomes. The π-shaped technique was faster than the MOBS method without significantly increasing the supplies costs. Large prospective studies are warranted., (© 2021 Wiley Periodicals LLC.)

Background: Among locally advanced gastric cancer (LAGC) patients, poor response to initial neoadjuvant chemotherapy (NAC) is associated with unfavorable outcomes; however, changing the postoperative therapy regimen in this group of patients is unclear. We compared the poor responders who continued the original protocols with that of patients who switched treatment after NAC plus D2 gastrectomy., Methods: Our study included LAGC patients who achieved tumor regression grade 3 according to the American Joint Committee on Cancer/College of American Pathologists system, after NAC, between December 2006 and December 2017 at our institution. Outcomes were overall survival (OS), progression-free survival (PFS), and adverse events during postoperative treatment. The propensity score matching method was used to match patients., Results: Overall, 160 patients were enrolled in the final analysis set, including 21 switched cases and 139 non-switched cases. A 1:2 matched cohort (21 switching vs. 42 non-switching) was generated to eliminate all confounding factors. No statistical differences were observed in OS and PFS, either in the whole patients (OS: log-rank p = 0.804; PFS: log-rank p = 0.943) or in the matched cohort (OS: log-rank p = 0.907; PFS: log-rank p = 0.670) between the two groups. Patients with changed regimens had a significantly higher rate of peripheral neurotoxicity (p = 0.045). Contrarily, a lower rate of overall adverse events was observed in the non-switching group with marginal significance (p = 0.069)., Conclusion: Adjusting to a non-cross-resistant regimen only by post-NAC pathological evaluation may not be sufficient for designing an effective treatment route for LAGC poor responders. Treatment change required a more scrutinized clinical track, which involved a multifaceted assessment., (© 2021. The Author(s).)

Objective: This study aimed to prospectively examine cardiac structure and function in the kainic acid-induced post-status epilepticus (post-KA SE) model of chronic acquired temporal lobe epilepsy (TLE), specifically to examine for changes between the pre-epileptic, early epileptogenesis and the chronic epilepsy stages. We also aimed to examine whether any changes related to the seizure frequency in individual animals., Methods: Four hours of SE was induced in 9 male Wistar rats at 10 weeks of age, with 8 saline treated matched control rats. Echocardiography was performed prior to the induction of SE, two- and 10-weeks post-SE. Two weeks of continuous video-EEG and simultaneous ECG recordings were acquired for two weeks from 11 weeks post-KA SE. The video-EEG recordings were analyzed blindly to quantify the number and severity of spontaneous seizures, and the ECG recordings analyzed for measures of heart rate variability (HRV). PicroSirius red histology was performed to assess cardiac fibrosis, and intracellular Ca 2+ levels and cell contractility were measured by microfluorimetry., Results: All 9 post-KA SE rats were demonstrated to have spontaneous recurrent seizures on the two-week video-EEG recording acquired from 11 weeks SE (seizure frequency ranging from 0.3 to 10.6 seizures/day with the seizure durations from 11 to 62 s), and none of the 8 control rats. Left ventricular wall thickness was thinner, left ventricular internal dimension was shorter, and ejection fraction was significantly decreased in chronically epileptic rats, and was negatively correlated to seizure frequency in individual rats. Diastolic dysfunction was evident in chronically epileptic rats by a decrease in mitral valve deceleration time and an increase in E/E` ratio. Measures of HRV were reduced in the chronically epileptic rats, indicating abnormalities of cardiac autonomic function. Cardiac fibrosis was significantly increased in epileptic rats, positively correlated to seizure frequency, and negatively correlated to ejection fraction. The cardiac fibrosis was not a consequence of direct effect of KA toxicity, as it was not seen in the 6/10 rats from separate cohort that received similar doses of KA but did not go into SE. Cardiomyocyte length, width, volume, and rate of cell lengthening and shortening were significantly reduced in epileptic rats., Significance: The results from this study demonstrate that chronic epilepsy in the post-KA SE rat model of TLE is associated with a progressive deterioration in cardiac structure and function, with a restrictive cardiomyopathy associated with myocardial fibrosis. Positive correlations between seizure frequency and the severity of the cardiac changes were identified. These results provide new insights into the pathophysiology of cardiac disease in chronic epilepsy, and may have relevance for the heterogeneous mechanisms that place these people at risk of sudden unexplained death., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Active constituents of Chinese yam peel (CYPE), namely, diosgenin (DOG), batatasin-I (BTS-I), batatasin-III (BTS-III), and yam polysaccharide (Y-PS), were extracted via an ultrasonic soaking strategy. The synergetic anticorrosion mechanism among these compounds for copper in artificial seawater (ASW) was clarified by gravimetric measurements, electrochemical evaluations, surface analyses, quantum chemical calculations under a dominant solvent model, and molecular dynamics (MD) simulations. The results of weight loss revealed that CYPE strongly inhibited the corrosion of copper in ASW, and the elevating temperature boosted the anticorrosion efficacy of CYPE. The inhibition efficiency could attain 96.33% with 900 mg/L CYPE in ASW at 298 K due to effective adsorption. CYPE simultaneously suppressed the anodic and cathodic reactions for copper in ASW, which could be categorized as the mixed-type corrosion inhibitor with the predominant anodic effect. Similar electrochemical kinetics was evidenced by electrochemical frequency modulation (EFM). Electrochemical impedance spectroscopy (EIS) indicated that CYPE prominently increased the charge-transfer resistance at the copper/electrolyte interface without altering the corrosion mechanism. Extending the immersion time was also conducive for CYPE to further minimize the corrosion of copper in ASW, which was demonstrated by the time-course polarization, EIS, and EFM tests. Owing to the adsorption of CYPE, the copper surface was well-protected and showed reduced wettability and limited variation of roughness. From the outcomes of quantum chemical calculations, global and local reactive descriptors of DOG implied the cross-linked deposition of actually formed dioscin on the copper surface; otherwise, those of BTS-I/-III showed the propensity for parallel adsorption, which could chemically anchor on the voids uncovered by dioscin and thereby synergistically inhibit the corrosion process. The adsorption orientations of DOG, BTS-I, and BTS-III were also consolidated by MD simulations. The findings of this study might be beneficial to inspire the development of eco-friendly corrosion inhibitors from plant wastes for copper in marine environments., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Sugarcane purple rind ethanolic extract (SPRE) was evaluated as an efficient corrosion inhibitor for carbon steel (C-steel) in 1 M HCl solution. Dynamic weight loss, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and frequency modulation (EFM) measurements were employed to evaluate the anticorrosive efficiency of SPRE, which was further validated by morphological and wettability analyses. The results of the weight loss tests showed that the inhibition efficiency ( η w ) for C-steel in HCl solution increased with an increase in the concentration of SPRE. An increase in temperature moderately impaired the anticorrosive efficacy of SPRE. The maximum η w of 96.2% was attained for C-steel in the inhibition system with 800 mg L -1 SPRE at 298 K. The polarization curves indicated that SPRE simultaneously suppressed the anodic and cathodic reactions for C-steel in HCl solution, which can be categorized as a mixed-type corrosion inhibitor with a predominant anodic effect. The corrosion current density ( i corr-P ) was monotonously reduced with an increase in the concentration of SPRE. The charge transfer resistance ( R ct ) was enhanced for C-steel in the inhibition solution with a restrained capacitive property due to the adsorption of SPRE. A high temperature caused partial desorption of SPRE on the C-steel surface and a slight increase in i corr-P and decrease in R ct . However, SPRE still fully maintained its morphology and wettability at 328 K. The electrochemical kinetics of C-steel in HCl solution without and with SPRE was also supported by EFM spectra. The adsorption of SPRE conformed to the Langmuir isotherm and increased the corrosion activation energy of C-steel. Complementing the experimental observations, calculations based on density functional theory indicated that the hydroxyl-substituted pyran moiety on the carthamin (CTM) and anthocyanin (ATC) constituents in SPRE hardly contributed to its reactive activity due to their adsorption processes. Therefore, CTM and ATC exhibited imperfect parallel adsorption on the Fe (100) plane according to the molecular dynamics simulation, while anthoxanthin (ATA) and catechinic acid (CCA) constituents exhibited a flat orientation on the iron surface., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Extraskeletal Ewing's sarcoma (EES) is one kind of rare malignant tumour which is always misdiagnosed preoperatively, especially for lesions located at endoceliac sites. This study analyse the clinicopathological features and outcomes of EES patients. The basic imaging characteristics of endoceliac lesions are also summarized., Methods: This study involved EES patients admitted to our centre between January 2000 and January 2020. Clinical data from patients with EES (n=25) and computed tomography (CT) features from endoceliac EES patients with available CT data (n=8) were retrospectively reviewed., Results: The sample comprised 18 males and 7 females with a median age of 30 years (range, 1-72 years). Seven patients had EES originating from surface sites and 18 had EES originating from endoceliac sites. The median tumour size was 8.0 cm (range, 2.5-17.0 cm). In total, 20% of patients had distant metastasis at diagnosis. In the univariate analyses, tumour size >8 cm, non-surgical treatment, and regional lymph nodes metastasis were risk factors for poor prognosis of EES. In the multivariate analysis, patients with larger tumour size and regional lymph node metastasis were independent predictors of overall survival (OS). Endoceliac EES cases frequently exhibited lobulated contour (87.5%), absence of calcification (75%), severe necrosis or cystic degeneration (75%), heterogeneous enhancement (100%), moderate enhancement (75%), ill-defined borderline (62.5%), and organ invasion (75%). Half of the patients with endoceliac EES had CT features of lymphadenopathy., Conclusions: Comprehensive understanding of the clinicopathological and imaging features of EES is beneficial for diagnosis, development of therapeutic strategies, and accurate prediction of prognosis for this rare malignant tumour., Competing Interests: Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tcr-21-607). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

Background: The prognostic values of preoperative tumor markers (TMs) remain elusive in patients with locally advanced gastric cancer (LAGC) after neoadjuvant chemotherapy treatment (NACT). This study aimed to assess and establish a novel scoring system incorporating carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4) to enhance prognostic accuracy for progression-free survival (PFS) and pathological response (pCR)., Methods: Patients' data were retrospectively analyzed from December 2006 to December 2017 in our center. The cutoff value of TMs was determined using the time-dependent receiver operating test characteristics method. These three TMs were allocated 1 point each for the post neoadjuvant chemotherapy combination of tumor markers (post-NACT CTM) scores. The training group comprised 533 patients, responsible for full analysis, and the validation group comprised 137 patients based on the selection protocol., Results: Of 533 enrolled patients, 138, 233, 117, and 45 patients scored 0, 1, 2, 3 respectively. The 3-year PFS rate Multivariate analysis revealed that post-NACT CTM score was an independent predictor of PFS (0 vs. 1, HR: 1.34, 95% CI: 0.92-1.96, P = 0.128; 0 vs. 2, HR: 2.03, 95% CI: 1.35-3.05, P = 0.001; 0 vs. 3, HR: 2.98, 95% CI: 1.83-4.86, P < 0.001). The time-dependent area under curve (AUC) revealed a consistent highest level for post-NACT CTM than other three single TMs. Lower post-NACT CTM score significantly correlated with higher pCR rate based on multivariate logistic regression (2/3 vs. 1, OR: 2.77, 95% CI: 0.90-8.53, P = 0.077; 2/3 vs. 0, OR: 4.33, 95% CI: 1.38-13.61, P = 0.012). A nomogram was formed with both internal and external validation., Conclusions: The post-NACT CTM score system served as a strong independent predictor for PFS and pCR in LAGC patients who received NACT. Further population-based studies are required to confirm our results., (© 2021. The Author(s).)

Background: The aim of this study was to study patients diagnosed with ovary metastasis from colorectal carcinoma (OM-CRC) regarding their clinical manifestations, pathological characteristics and developments based on the results of computed tomography (CT)., Methods: Research was conducted with OM-CRC admissions to our facility during the period of January, 2000 to January, 2020, with examinations of both patients and imaging statistics., Results: A group of 21 female participants with a median age of 54-year-old, ranging from 48 to 68 years old, were investigated. In the univariate analyses, synchronous metastasis and R2 resection (macroscopic residual lesions) during cytoreductive surgery (CRS) were shown to be negatively associated with the OM-CRC prognosis. Results of the multivariate analysis showed that R2 resection during CRS was the only independent predictor of the overall survival (OS) rate as well as the progression-free survival (PFS) rate. OM-CRC cases frequently exhibited a well-defined borderline (90.9%), predominantly cystic ovarian mass (90.9%), heterogeneous enhancement (72.3%), moderate enhancement (63.6%), peritoneal implantation (81.8%) and an absence of lymphadenopathy (90.9%)., Conclusions: It is important to develop a thorough comprehension of the pathological characteristics as well as developments of OM-CRC, in order to understand its diagnosis, develop useful therapeutic interventions, and predict accurate prognosis. Nevertheless, OM-CRC is an uncommon malignant ovarian tumor and a good prognosis requires a CRS without macroscopic residual lesions, as a significant finding of our study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tcr-21-605). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

Background: Until now, little is known about the benefit of laparoscopic total gastrectomy (LTG) after neoadjuvant chemotherapy (NACT). This study was designed to compare the safety and efficacy of the LTG versus the open total gastrectomy (OTG) approach after NACT treatment in patients with advanced gastric cancer (AGC)., Methods: This study involved a cohort of 145 patients with AGC who underwent total gastrectomy after NACT at our centre between April 2013 and August 2018 including 24 cases of LTG and 121 OTG. The baseline characteristics were matched based on 1:2 balanced propensity score-matching method., Results: Sixty-nine marched cases were finally analysed (23 LTG vs. 46 OTG). All patients underwent R0 resection. Compared to the OTG group, the LTG group had a longer surgery duration (P<0.001), but a shorter incision length (P<0.001) and less intravenous patient-controlled analgesia (IV-PCA) time after surgery (P=0.027). No statistical differences were observed in terms of blood loss, retrieved lymph nodes (LNs), resection margin, length of stay, postoperative pain intensity, and complications (P>0.05)., Conclusions: LTG had comparable safety and histological findings to OTG after NACT in the perioperative period; however, LTG is less invasive and patients can benefit from less IV-PCA use. Further research is needed to investigate long-term effects., Keywords: Gastric cancer (GC); neoadjuvant chemotherapy (NACT); safety; laparoscopic technique., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-374). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Rationale: The clinical prognosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) patients is poor. Therefore, effective treatment is still a challenge at present. Moreover, little is known about the value of radiotherapy in the treatment of PTCL-NOS., Patient Concerns: A 55-year-old male patient with eating difficulties and progressive exacerbation for 3 months was diagnosed as non-Hodgkin's lymphoma. Airway compression occurred after 2 cycles of first line treatment with cyclophosphamide-Adriamycin-vincristine-prednisone regimen, radiotherapy (48Gy/24f) was given as the second line therapy., Diagnosis: After radiotherapy, the patient complained that mild intermittent dysphagia still existed. Endoscopic biopsy of the upper digestive tract confirmed necrotic material and superficial squamous epithelial mucosa, suggesting esophageal stricture after radiotherapy, which was indistinguishable from tumor residue., Interventions: The patient received anti-inflammatory treatment outside the hospital and did not receive any other special treatment., Outcomes: The symptoms of dysphagia disappeared and the focus showed complete response (CR). As of October 1, 2020, the patient has been diagnosed with PTCL-NOS for more than 57 months and the overall survival (OS) have not been achieved., Lessons: Radiotherapy has obvious and rapid anti-tumor effect on cyclophosphamide-Adriamycin-vincristine-prednisone refractory PTCL-NOS. At the same time, hollow organs after radiotherapy can lead to lumen stenosis and the symptoms of suspected recurrence which is difficult to distinguish only from the imaging findings., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The duration and the optimal time to adjuvant chemotherapy (TAC) in locally advanced gastric cancer (LAGC) have net not been sufficiently demonstrated. Sequential adjuvant chemotherapy (AC) after neoadjuvant chemotherapy plus gastrectomy is increasingly utilized, making the question more complicated., Patients and Methods: Data were collected from patients with LAGC who underwent 5-Fu-based doublet regimens as adjuvant treatment after gastrectomy in a single-center database. TAC and duration (cycles) were used to evaluate survival outcomes., Results: A total of 816 patients were included. Patients received over six cycles and TAC less than 42 days significantly correlated with better survival (log-rank P trend <0.001). The analysis of TAC and number cycles were separately applied in perioperative chemotherapy (PEC) and postoperative chemotherapy (POC) group using Cox regression. The number of cycles revealed a statistical significance improving OS rate both in POC (HR=0.904, 95% CI=0.836-0.977, P =0.011) and PEC (HR=0.887, 95% CI=0.798-0.986, P =0.026), while only in POC did the TAC show an increasing trend of risk with borderline significance (OS: HR=1.008, 95% CI=0.999-1.018, P =0.094; PFS: HR=1.009, 95% CI=1.000-1.018, P =0.055). A spline model demonstrates the less improvement in survival after cycles of chemotherapy reaching six., Conclusion: Our findings suggest that TAC is more likely to downregulate the survival benefit in POC rather than PEC, while overall survival is susceptible to cumulative cycles of chemotherapy in both groups. Furthermore, six cycles of chemotherapy tended to reach the maximum survival benefits. Prospective confirmation is required., Competing Interests: All authors declare that they have no conflicts of interest., (© 2021 Liu et al.)

Locally advanced upper urinary tract urothelial carcinoma (UTUC) exhibits high recurrence and metastasis rates even after radical nephroureterectomy. Adjuvant immunotherapy can be a reasonable option, and a simple, low-cost, and effective biomarker is further needed. Stromal tumor-infiltrating lymphocytes (sTILs) has been demonstrated as a prognostic and predictive biomarker in various tumor types, but not yet in locally advanced UTUC. In this multicenter, real-world and retrospective study, we tried to investigate the prognostic role of sTIL and its correlation with the PD-L1/PD-1/CD8 axis by reviewing the clinicopathologic variables of 398 locally advanced UTUC patients at four high-volume Chinese medical centers. sTIL density was evaluated with standardized methodology on H&E sections, and patients were stratified by the cutoff of sTIL (50%). Results showed that high sTIL indicated improved survival (CSS, p = .022; RFS, p = .015; DFS, p = .004), and was an independent predictor of better CSS ( HR , 0.577; 95% CI, 0.391-0.851; p = .006), RFS ( HR , 0.613; 95% CI 0.406-0.925; p = .020) and DFS ( HR , 0.609; 95% CI, 0.447-0.829; p = .002). A strongly positive correlation between sTIL density and the expression level of PD-1/PD-L1/CD8 axis was observed. We also found that aristolochic acid (AA) exposure was associated with increased sTIL and elevated PD-L1 expression, indicating that AA-related UTUC might be a distinct subgroup with unique tumor microenvironment characteristics. Our results show that sTIL can be an easily acquired biomarker for prognostic stratification in locally advanced UTUC., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: The relationship between time to surgery (TTS) and survival benefit is not sufficiently demonstrated by previous studies in locally advanced gastric cancer (LAGC). This study aims to assess the impact of TTS after neoadjuvant chemotherapy (NACT) on long-term and short-term outcomes in LAGC patients., Methods: Data were collected from patients with LAGC who underwent NACT between January 2007 and January 2018 at our institution. Outcomes assessed were long-term survival, pathologic complete response (pCR) rate, and postoperative complications., Results: This cohort of 426 patients was divided into five groups by weeks of TTS. Under cox regression, compared to other groups, the 22-28 days and 29-35 days groups revealed a better OS (≤21 vs. 22-28 days: HR 1.54, 95% CI = 0.81-2.93, P = 0.185; 36-42 vs. 22-28 days: HR 2.20, 95% CI = 1.28-3.79, P = 0.004; 43-84 vs. 22-28 days: HR 1.83, 95% CI = 1.09-3.06, P = 0.022) and PFS (≤21 vs. 22-28 days: HR 1.54, 95% CI = 0.81-2.93, P = 0.256; 36-42 vs. 22-28 days: HR 2.20, 95% CI = 1.28-3.79, P = 0.111; 43-84 vs. 22-28 days: HR 1.83, 95% CI = 1.09-3.06, P = 0.047). Further analysis revealed a better prognosis in patients with TTS within 22-35 days (OS: HR 1.78 95% CI = 1.25-2.54, P = 0.001; PFS: HR 1.49, 95% CI = 1.07-2.08, P = 0.017). Postoperative stay was significantly higher in the ≤21 days group, while other parameters revealed no statistical significance (P > 0.05). Restricted cubic spline depicted the nonlinear relationship between TTS and OS/PFS., Conclusion: Patients who received surgery within 3-5 weeks experienced the maximal survival benefit without an increase in postoperative complications or lowering the rate of pCR. Further investigations are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wang, Liu, Shan, Ying, Zhang, Li, Jia, Li and Ji.)

Purpose: Doublet combination chemotherapy is commonly considered a second-line treatment for advanced non-small cell lung cancer (NSCLC) in China. This multi-institutional retrospective analysis evaluated and compared the efficacy between combination and mono-therapy after platinum-based first-line chemotherapy in Chinese patients with advanced NSCLC., Methods: We retrospectively reviewed 335 patients who received second-line chemotherapy for advanced NSCLC. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), response rate (RR) and toxicity. Treatment-free interval (TFI) was used for further stratification analysis. The Cox proportional hazards model was used for multivariate analysis., Results: Two hundred and fifty-three patients received doublet combination chemotherapy and 82 received single-agent chemotherapy. PFS was significantly prolonged in combination group compared to single-agent group (median 5.70 vs 3.70 months; HR 0.62; 95% CI 0.45-0.85; p < 0.001). The RR was significantly higher in the combination group than in the single-agent group (29.25% vs. 10.98%; p = 0.001). OS was also prolonged in combination group versus single-agent group (median 13.30 vs. 11.45 months, respectively; HR 0.70; 95% CI 0.52-0.95; p = 0.023). Among patients with TFI of ≥ 6 months, PFS and OS of the combination group were significantly increased than the single-agent group (median PFS, 6.67 vs. 3.80 months, p = 0.002; median OS, 13.60 vs. 11.45 months, p = 0.013). Grade III/IV toxicity was similar between the two groups (p = 0.113). Through multivariate analyses, we found that Eastern Cooperative Oncology Group (ECOG) score (p < 0.001), further-line treatment (p < 0.001) and combination chemotherapy (p = 0.024) were the independent prognostic factors., Conclusion: Compared with mono-therapy, combination chemotherapy was a better second-line option for Chinese patients with good performance status, especially in those with TFI of ≥ 6 months.

Purpose: This study aimed to evaluate the efficiency of several parameters, including the neutrophil-to-lymphocyte ratio (NLR) obtained from preoperative routine blood examination, either alone or as an adjunct to the carbohydrate antigen 19-9 (CA19-9), for the diagnosis of gallbladder carcinoma (GBC)., Patients and Methods: Data from 123 patients with gallbladder cholesterol polyps (GCP), 80 with gallbladder adenoma (GA), and 103 with GBC were reviewed retrospectively. Receiver operating characteristic analysis was used to assess the sensitivity, specificity, and clinical value of the NLR, CA19-9, and their combination., Results: Values of measured indicators were significantly higher in GBC patients than in GCP or GA patients but there were no significant differences between GCP and GA patients. The combination of NLR and CA19-9 had the best diagnostic efficiency for differentiating GBC from benign lesions with 74.8% sensitivity and 89.7% specificity. However, the NLR showed no significant difference between mid-to-advanced stage and early-to-mid stage GBC. The combination of NLR and CA19-9 (53.7% sensitivity and 88.9% specificity) did not reveal any advantages over CA19-9 alone (63.0% sensitivity and 89.0% specificity) in distinguishing different stages of GBC., Conclusion: NLR and CA19-9, and their combination-parameters that are easily obtained preoperatively-have potential as diagnostic markers for GBC., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Chen et al.)

Purpose: We investigated which obesity-associated parameters can better predict the risk of anastomotic leakage (AL) in rectal cancer patients that underwent anterior resection of the rectum. Method: Patients ( n  = 589) who underwent anterior resection of the rectum with a primary anastomosis were included in this study, including 44 patients with AL and 545 without AL. Univariate analysis was used to compare demographic characteristics and to select risk factors that were used in one-to-one propensity score matching (PSM). Obesity-associated parameters, including preoperative body mass index (BMI), visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA), VFA/TFA ratio, serum cholesterol, and triglycerides, were compared between the two groups after PSM. Results: Sex, neoadjuvant chemotherapy, operation time, and anastomosis level from the anal verge were risk factors for AL ( p  < .05). After the PSM, BMI, VFA, SFA, TFA, VFA/TFA, and serum cholesterol showed no significant difference between the two group ( p  > .05). However, the level of serum triglycerides was an independent risk factor for AL ( p  = .024, odds ratio = 2.95). Conclusions: Serum triglycerides have potential as a predictive indicator for AL, which may improve the treatment and outcomes of patients with AL.

Herein, we describe an efficient copper-catalyzed coupling of sulfonamides with alkylamines to synthesize ( E )- N -sulfonylformamidines. The reaction is accomplished under mild conditions without the use of a corrosive acid or base as an additive. It tolerates a broad scope of substrates and generates the products with exclusive ( E )-stereoselectivity.

A novel ruthenium(II) polypyridyl complex bearing 1,8-naphthyridine was successfully designed and synthesized. This complex was fully characterized by EI-HRMS, NMR, and elemental analyses. The recognition properties of the complex for various metal ions were investigated. The results suggested that the complex displayed high selectivity and sensitivity for Cu 2+ and Fe 3+ ions with good anti-interference in the CH 3 CN/H 2 O (1:1, v / v ) solution. The fluorescent chemosensor showed obvious fluorescence quenching when the Cu 2+ and Fe 3+ ions were added. The detection limits of Cu 2+ and Fe 3+ were 39.9 nmol/L and 6.68 nmol/L, respectively. This study suggested that this Ru(II) polypyridyl complex can be used as a high selectivity and sensitivity fluorescent chemosensor for Cu 2+ and Fe 3+ ions.

The current prognosis of glioma patients remains poor after intensive multimodal treatments, which is partially due to the existence of the blood-brain tumor barrier (BBTB). In the present study, a novel "bifunctional ligand" (termed D VS) was developed by retro-inverso isomerization. D VS is a ligand of integrins highly expressed on glioma cells and tumor neovasculature. D VS exhibited exceptional stability in serum and demonstrated significantly higher targeting efficiency for glioma and HUVEC cells compared with the parent L-peptide. As a result, D VS modified micelles ( D VS-MS) exhibited high encapsulation efficiency of doxorubicin, ideal size distribution, and sustained release behavior of the payload. In vivo studies showed that D VS-MS could target and efficiently deliver fluorescence to tumor cells and tumor vasculature not only in the mice bearing subcutaneous tumors but also in those bearing intracranial tumors. Moreover, doxorubicin loaded D VS modified micelles exerted potent tumor growth inhibitory activity against subcutaneous and intracranial human glioma in comparison to drug loaded plain micelles and L VS modified micelles. Therefore, D VS appears to be a suitable targeting ligand with potential applications for glioma targeted drug delivery.

Surgical resection is a mainstay in the treatment of malignant brain tumors. Surgeons, however, face great challenges in distinguishing tumor margins due to their infiltrated nature. Here, a pair of gold nanoprobes that enter a brain tumor by crossing the blood-brain barrier is developed. The acidic tumor environment triggers their assembly with the concomitant activation of both magnetic resonance (MR) and surface-enhanced resonance Raman spectroscopy (SERRS) signals. While the bulky aggregates continuously trap into the tumor interstitium, the intact nanoprobes in normal brain tissue can be transported back into the blood stream in a timely manner. Experimental results show that physiological acidity triggers nanoparticle assembly by forming 3D spherical nanoclusters with remarkable MR and SERRS signal enhancements. The nanoprobes not only preoperatively define orthotopic glioblastoma xenografts by magnetic resonance imaging (MRI) with high sensitivity and durability in vivo, but also intraoperatively guide tumor excision with the assistance of a handheld Raman scanner. Microscopy studies verify the precisely demarcated tumor margin marked by the assembled nanoprobes. Taking advantage of the nanoprobes' rapid excretion rate and the extracellular acidification as a hallmark of solid tumors, these nanoprobes are promising in improving brain-tumor surgical outcome with high specificity, safety, and universality., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Even though opening endothelial tight junctions is an efficient way to up-regulate brain drug delivery, the extravasation of blood-borne components from the compromised tight junctions can result in adverse consequences such as edema and neuronal injuries. In this work, we developed a nanoagonist that temporarily opened tight junctions by signaling adenosine 2A receptor, a type of G protein-coupled receptor expressed on brain capillary endothelial cells. Magnetic resonance imaging demonstrated remarkable blood-brain barrier permeability enhancements and significantly increased brain uptakes of both small molecular and macromolecular paramagnetic agents after nanoagonist administration. Gamma ray imaging and transmission electron microscope observed tight junction opening followed by spontaneous recovery after nanoagonist treatment. Immunofluorescence staining showed the unspoiled basal membrane, pericytes and astrocyte endfeet that enwrapped the vascular endothelium. Importantly, edema, apoptosis and neuronal injuries observed after hypertonic agent mediated tight junction-opening were not observed after nanoagonist intervention. The uncompromised neurovascular units may prevent the leakage of blood-borne constituents into brain parenchyma and accelerate tight junction recovery. Considering blood-brain barrier impermeability is a major obstacle in the treatment of central nervous system diseases, nanoagonist-mediated tight junction opening provides a promising strategy to enhance brain drug delivery with minimized adverse effects.