Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.

Genetic dissection of ten photosynthesis-related traits based on InDel- and SNP-GWAS in soybean.

KEY MESSAGE: A total of 416 InDels and 112 SNPs were significantly associated with soybean photosynthesis-related traits. GmIWS1 and GmCDC48 might be related to chlorophyll fluorescence and gas-exchange parameters, respectively. Photosynthesis is one of the main factors determining crop yield. A better understanding of the genetic architecture for photosynthesis is of great significance for soybean yield improvement. Our previous studies identified 5,410,112 single nucleotide polymorphisms (SNPs) from the resequencing data of 219 natural soybean accessions. Here, we identified 634,106 insertions and deletions (InDels) from these 219 accessions and used these InDel variations to perform principal component and linkage disequilibrium analysis of this population. The genome-wide association study (GWAS) were conducted on six chlorophyll fluorescence parameters (chlorophyll content, light energy absorbed per reaction center, quantum yield for electron transport, probability that a trapped exciton moves an electron into the electron transport chain beyond primary quinone acceptor, maximum quantum yield of photosystem II primary photochemistry in the dark-adapted state, performance index on absorption basis) and four gas-exchange parameters (intercellular carbon dioxide concentration, stomatal conductance, net photosynthesis rate, transpiration rate) and revealed 416 significant InDels and 112 significant SNPs. Based on GWAS results, GmIWS1 (encoding a transcription elongation factor) and GmCDC48 (encoding a cell division cycle protein) with the highest expression in the mapping region were determined as the candidate genes responsible for chlorophyll fluorescence and gas-exchange parameters, respectively. Further identification of favorable haplotypes with higher photosynthesis, seed weight and seed yield were carried out for GmIWS1 and GmCDC48. Overall, this study revealed the natural variations and candidate genes underlying the photosynthesis-related traits based on abundant phenotypic and genetic data, providing valuable insights into the genetic mechanisms controlling photosynthesis and yield in soybean.

Brain structure and functional connectivity linking childhood cumulative trauma to COVID-19 vicarious traumatization.

BACKGROUND: The COVID-19 pandemic has caused some individuals to experience vicarious traumatization (VT), an adverse psychological reaction to those who are primarily traumatized, which may negatively impact one's mental health and well-being and has been demonstrated to vary with personal trauma history. The neural mechanism of VT and how past trauma history affects current VT remain largely unknown. This study aimed to identify neurobiological markers that track individual differences in VT and reveal the neural link between childhood cumulative trauma (CCT) and VT. METHODS: We used structural and resting-state functional magnetic resonance imaging before the pandemic to identify prospective brain markers for COVID-related VT by correlating individuals' VT levels during the pandemic with the gray matter volume (GMV) and seed-based resting-state functional connectivity (RSFC) and examined how these brain markers linked CCT to VT in a sample of general young adults (N = 115/100). RESULTS: Whole-brain GMV-behavior correlation analysis showed that VT was positively associated with GMV in the right dorsolateral prefrontal gyrus (DLPFC). Using the cluster derived from the GMV-behavior correlation analysis as the seed region, we further revealed that the RSFC between the right DLPFC and right precuneus was negatively associated with VT. Importantly, the right DLPFC volume and DLPFC-precuneus RSFC mediated the effect of CCT on VT. These findings remained unaffected by factors such as family socioeconomic status, other stressful life events, and general mental health. CONCLUSIONS: Overall, our study presents structural and functional brain markers for VT and highlights these brain-based markers as a potential neural mechanism linking CCT to COVID-related VT, which has implications for treating and preventing the development of trauma-related mental disorders.

CircMETTL15 induces TMTC3 production by absorbing miR-944 to promote hepatocellular carcinoma cell malignancy.

Previous data have suggested the involvement of circular RNA (circRNA) in hepatocellular carcinoma (HCC) progression. Up to now, the effect of circMETTL15 on HCC development remains unknown. This study aims to analyze the function of circMETTL15 in HCC development and the underlying mechanism. RNA expression of circMETTL15, miR-944, and transmembrane O-mannosyltransferase targeting cadherins 3 (TMTC3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated by Western blot analysis assay or immunohistochemistry assay. Cell proliferation was investigated by cell counting kit-8 assay, 5-Ethynyl-29-deoxyuridine (EdU) assay, and cell colony formation assay. Cell migration and invasion were assessed by wound-healing assay and transwell assay, respectively. Angiogenic capacity was analyzed by tube formation assay. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to identify the interplay between miR-944 and circMETTL15 or TMTC3. Xenograft mouse model assay was conducted to reveal the effect of circMETTL15 on tumor formation in vivo. CircMETTL15 and TMTC3 expression were significantly upregulated, while miR-944 expression was downregulated in HCC tissues and cells. CircMETTL15 knockdown led to decreased cell proliferation, migration, invasion, and tube formation. Besides, the inhibitors of miR-944, a target miRNA of circMETTL15, partially restored circMETTL15 silencing-mediated effects on the proliferation, migration, invasion, and tube formation of HCC cells. MiR-944 overexpression also inhibited HCC cell malignancy by targeting TMTC3. Furthermore, circMETTL15 absence inhibited tumor formation by regulating miR-944 and TMTC3 in vivo. In conclusion, circMETTL15 induced HCC development through the miR-944/TMTC3 pathway, raising the potential of circMETTL15 as a target for HCC therapy.

Neuroanatomical signatures associated with dispositional optimism predict COVID-19-related posttraumatic stress symptoms.

The COVID-19 pandemic has been increasingly documented to cause negative impacts on mental health outcomes, e.g. posttraumatic stress symptoms (PTSS). Dispositional optimism ("optimism" hereinafter), a crucial psychological characteristic defined by positive expectancies for future outcomes, is considered to provide remarkable protection against PTSS. Accordingly, this study was designed to identify neuroanatomical signatures of optimism and further examine the mechanism through which optimism protects against COVID-19-specific PTSS. Here, 115 volunteers from a general population of university students completed MRI scans and optimism tests before (October 2019-January 2020) and after (February-April 2020) the onset of the COVID-19 pandemic. Whole-brain voxel-based morphometry analysis showed that a region from the dorsal anterior cingulate cortex (dACC) to the dorsomedial prefrontal cortex (dmPFC) was associated with optimism. Further seed-based structural covariance network (SCN) analysis using partial least-squares correlation found an optimism-linked SCN covarying with the combined dACC and dmPFC (the dACC-dmPFC). Additionally, mediation analyses revealed that the dACC-dmPFC volume and its SCN impacted COVID-19-specific PTSS through optimism. Our findings deepen the understanding of optimism and have the potential to identify vulnerable individuals during the COVID-19 pandemic or similar future events, as well as to guide optimism-related neural interventions to prevent and alleviate PTSS.

Epidemiological variations and trends in glaucoma burden in the Belt and Road countries.

BACKGROUND: Analyzing the glaucoma burden in "Belt and Road" (B&R) countries based on age, gender, and risk factors from 1990 to 2019 in order to provide evidence for future prevention strategies. METHODS: We applied global burden of disease(GBD) 2019 to compare glaucoma prevalence and Years lived with disabilities (YLDs) from 1990 to 2019 in the B&R countries. Trends of disease burden between 1990 and 2019 were evaluated using the average annual percent change and the 95% uncertainty interval (UI) were reported. RESULTS: From 1990 to 2019, most B&R countries showed a downward trend in age-standardized prevalence and YLDs (all P < 0.05). Additionally, only the age-standardized YLDs in males of Pakistan has a 0.35% increase (95%CI:0.19,0.50,P < 0.001), and most B&R countries has a decline(all P < 0.05) in age-standardized YLDs in every 5 years age group after 45 years old except for Pakistan(45-79 years and > 85 years), Malaysia(75-84 years), Brunei Darussalam(45-49 years), Afghanistan(70-79 years). Finally, in all Central Asian countries, the age-standardized YLDs due to glaucoma caused by fasting hyperglycemia demonstrated have an increase between 1990 and 2019 (all P < 0.05), but Armenia and Mongolia have a decrease between 2010 and 2019 (all P < 0.05). CONCLUSION: The prevalence of glaucoma continues to pose a significant burden across regions, ages, and genders in countries along the "B&R". It is imperative for the "B&R" nations to enhance health cooperation in order to collaboratively tackle the challenges associated with glaucoma.

Mechanochemical Backbone Editing for Controlled Degradation of Vinyl Polymers.

The chemically inert nature of fully saturated hydrocarbon backbones endows vinyl polymers with desirable durability, but it also leads to their significant environmental persistence. Enhancing the sustainability of these materials requires a pivotal yet challenging shift: transforming the inert backbone into one that is degradable. Here, we present a versatile platform for mechanochemically editing the fully saturated backbone of vinyl polymers towards degradable polymer chains by integrating cyclobutene-fused succinimide (CBS) units along backbone through photo-iniferter reversible addition-fragmentation chain-transfer (RAFT) copolymerization. Significantly, the evenly insertion of CBS units does not compromise thermal or chemical stability but rather offers a means to adjust the properties of polymethylacrylate (PMA). Meanwhile, reactive acyclic imide units can be selectively introduced to the backbone through mechanochemical activation (pulse ultrasonication or ball-milling grinding) when required. Subsequent hydrolysis of the acyclic imide groups enables efficient degradation, yielding telechelic oligomers. This approach holds promise for inspiring the design and modification of more environmentally friendly vinyl polymers through backbone editing.

Interfacial Engineering of Co3 O4 /Fe2 O3 Nano-Heterostructure Toward Superior Li-O2 Batteries.

A major issue with Li-O2 batteries is their slow oxygen reduction and evolution kinetics, necessitating catalysts with high catalytic activity to improve reaction kinetics and cycle stability. Herein, a nano-heterostructured catalyst composed of Co3 O4 and Fe2 O3 (Co3 O4 /Fe2 O3 ) with a porous rod morphology is achieved through an interfacial engineering strategy by constructing Fe2 O3 on the Co3 O4 surface, which can function as a high-performance cathode in order to efficiently encourage the oxygen reduction and evolution while also reduce the battery polarization during charging and discharging. The density functional theory (DFT) calculations show the differences in charge density at the interface of nano-heterostructures, demonstrating the occurrence of an electron transfer process in the interface region of Co3 O4 and Fe2 O3 , implying a strong electronic coupling transfer, and in turn changing the electronic structure of the Co3 O4 . This significantly reduces the adsorption energy of LiO2 intermediates, thereby effectively lowering the overpotential. The resultant Li-O2 battery has larger discharge specific capacity, lower overpotential for the efficient oxygen evolution/reduction, as well as good cycling stability of 280 cycles. This work demonstrates an effective method to fabricate the nano-heterostrucutred materials with enhanced catalytic efficiency for advanced energy applications.

Psychometric testing of the 10-item perceived stress scale for Chinese nurses.

BACKGROUND: Nurses bear a lot of stressors at work. The 10-item Perceived Stress Scale (PSS-10) is a widely used self-reported scale for measuring the global perception of stress. However, there is a lack of use of the PSS-10 in Chinese nurses. This study aimed to test the psychometric properties of the PSS-10 among Chinese nurses. METHODS: A total of 708 Chinese nurses completed the PSS-10, the Big Five Inventory (BFI), and the Depression Anxiety and Stress Scale (DASS). Confirmatory factor analysis (CFA) tested the factor structure of the PSS-10. Cronbach's α and test-retest correlation examined the scale reliability. Pearson correlation and hierarchical regression analyses tested the convergent, discriminant and criterion validity of the PSS-10. RESULTS: CFA revealed that a two-factor model fits the structure of the PSS-10 in Chinese nurses (χ2/df = 6.25, p < 0.001; comparative fit index [CFI] = 0.94, non-normal fit index [NNFI] = 0.92, Tucker-Lewis index [TLI] = 0.91, root mean square error of approximation [RMSEA] = 0.08, standardized root mean square residual [SRMR] = 0.05). The scale demonstrated adequate internal consistency (α = 0.86) and test-retest reliability (r = 0.66, p < 0.001), satisfactory convergent and discriminant validity with relations to Big Five personalities, as well as good criterion validity such that the PSS-10 score could explain incremental variance in predicting anxiety, depression and stress. CONCLUSIONS: Our findings suggest that PSS-10 is a reliable and valid measure of perceived stress among Chinese nurses and can be used in future research and practice on stress management and coping in Chinese nurses.

Patterns of a structural covariance network associated with dispositional optimism during late adolescence.

Dispositional optimism (hereinafter, optimism), as a vital character strength, reflects the tendency to hold generalized positive expectancies for future outcomes. A great number of studies have consistently shown the importance of optimism to a spectrum of physical and mental health outcomes. However, less attention has been given to the intrinsic neurodevelopmental patterns associated with interindividual differences in optimism. Here, we investigated this important question in a large sample comprising 231 healthy adolescents (16-20 years old) via structural magnetic resonance imaging and behavioral tests. We constructed individual structural covariance networks based on cortical gyrification using a recent novel approach combining probability density estimation and Kullback-Leibler divergence and estimated global (global efficiency, local efficiency and small-worldness) and regional (betweenness centrality) properties of these constructed networks using graph theoretical analysis. Partial correlations adjusted for age, sex and estimated total intracranial volume showed that optimism was positively related to global and local efficiency but not small-worldness. Partial least squares correlations indicated that optimism was positively linked to a pronounced betweenness centrality pattern, in which twelve cognition-, emotion-, and motivation-related regions made robust and reliable contributions. These findings remained basically consistent after additionally controlling for family socioeconomic status and showed significant correlations with optimism scores from 2.5 years before, which replicated the main findings. The current work, for the first time, delineated characteristics of the cortical gyrification covariance network associated with optimism, extending previous neurobiological understandings of optimism, which may navigate the development of interventions on a neural network level aimed at raising optimism.

The effects of posture on mind wandering.

Using a reading comprehension task, we explored whether body postures would influence mind wandering, a universal internally self-generated activity. Specifically, participants were instructed to perform a reading comprehension task under three postural conditions (lying supine, sitting, and standing upright). Probe-caught technique with prompts presented at irregular intervals was adapted to measure the frequency of mind wandering. Self-caught method was used to measure the meta-awareness of mind wandering by self-reports. Results indicated that the radio of mind wandering was significantly greater in lying than standing and sitting, but the meta-awareness of it was not different among three postures. Moreover, the reading performance, an indirect indicator of executive control, decreased in lying compared to standing and sitting. We suggested that the increase of mind wandering in lying posture may due to the dysfunction of executive control, which also results in the redistribution of cognitive resources. Suggestions for future research are proposed.

Hand-assisted laparoscopic resection versus total laparoscopic gastric surgery for primary gastric gastrointestinal stromal tumors (GISTs): an analysis from a high-volume institution.

BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) is technically feasible and associated with favorable outcomes. We compared the clinical efficacy of hand-assisted laparoscopic surgery (HLS) and total laparoscopic surgery (TLS) for gastric GISTs. METHODS: We retrospectively analyzed the clinical data of 69 consecutive patients diagnosed with a gastric GIST in a tertiary referral teaching hospital from December 2016 to December 2020. Surgical outcomes were compared between two groups. RESULTS: Fifty-three patients (TLS group: n = 36; HLS group: n = 17) were included. The mean age was 56.9 and 58.1 years in the TLS and HLS groups, respectively. The maximum tumor margin was significantly shorter in the HLS group than in the TLS group (2.3 ± 0.9. vs. 3.0 ± 0.8 cm; P = 0.004). The operative time of the HLS group was significantly shorter than that of the TLS group (70.6 ± 19.1 min vs. 134.4 ± 53.7 min; P < 0.001). The HLS group had less intraoperative blood loss, a shorter time to first flatus, and a shorter time to fluid diet than the TLS group (P < 0.05). No significant difference was found between the groups in the incidence or severity of complications within 30 days after surgery. Recurrence or metastasis occurred in four cases (HLS group; n = 1; TLS group; n = 3). CONCLUSIONS: This study demonstrated that compared with TLS, HLS for gastric GISTs has the advantages of simpler operation, shorter operative time, and faster postoperative recovery.

Hydrogen sulphide reduced the accumulation of lipid droplets in cardiac tissues of db/db mice via Hrd1 S-sulfhydration.

Accumulation of lipid droplets (LDs) induces cardiac dysfunctions in type 2 diabetes patients. Recent studies have shown that hydrogen sulphide (H2 S) ameliorates cardiac functions in db/db mice, but its regulation on the formation of LDs in cardiac tissues is unclear. Db/db mice were injected with NaHS (40 µmol·kg-1 ) for twelve weeks. H9c2 cells were treated with high glucose (40 mmol/L), oleate (200 µmol/L), palmitate (200 µmol/L) and NaHS (100 µmol/L) for 48 hours. Plasmids for the overexpression of wild-type Hrd1 and Hrd1 mutated at Cys115 were constructed. The interaction between Hrd1 and DGAT1 and DGAT2, the ubiquitylation level of DGAT1 and 2, the S-sulfhydration of Hrd1 were measured. Exogenous H2 S ameliorated the cardiac functions, decreased ER stress and reduced the number of LDs in db/db mice. Exogenous H2 S could elevate the ubiquitination level of DGAT 1 and 2 and increased the expression of Hrd1 in cardiac tissues of db/db mice. The S-sulfhydration of Hrd1 by NaHS enhanced the interaction between Hrd1 and DGAT1 and 2 to inhibit the formation of LD. Our findings suggested that H2 S modified Hrd1 S-sulfhydration at Cys115 to reduce the accumulation of LDs in cardiac tissues of db/db mice.

Accessing Divergent Main-Chain-Functionalized Polyethylenes via Copolymerization of Ethylene with a CO2/Butadiene-Derived Lactone.

Carbon dioxide (CO2) has been used as a sustainable comonomer in the synthesis of different functional polymers including polycarbonates, polyurea, and polyurethane. Until today, despite the great interest, little success has been made for incorporating CO2 into the most widely used polyethylene materials. Herein, we report the incorporation of CO2 to polyethylenes through the copolymerization of ethylene with a CO2/butadiene-derived lactone, 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-one (EVP). Two-types of main-chain-functionalized polyethylenes can be synthesized through different copolymerization strategies. Palladium-catalyzed coordination/insertion copolymerization furnished polyethylenes bearing unsaturated lactones, while radical copolymerization afforded polyethylenes bearing bicyclic lactones. Modification of the polyethylene chains was successfully accomplished through Michael addition or aminolysis. This highly versatile copolymerization protocol provides access to a diverse range of polyethylene materials made from ethylene, CO2, and 1,3-butadiene.

One-Pot Synthesis of Polyethylene-Based Block Copolymers via a Dual Polymerization Pathway.

Polyethylene-poly(methyl acrylate) multiblock copolymers were obtained using a catalyst system consisting of a pentamethylcyclopentadienyl cobalt complex (CoIII(η5-C5H5)P(OMe)3I2) and iso-butyl modified methylaluminoxane (MMAO). As the chain-growth mechanism, the self-switching between organometallic-mediated radical polymerization (OMRP) and coordination-insertion polymerization (CIP) is suggested. As a possible polymerization mechanism, we propose that (1) the methyl and iso-butyl groups transfer from Al to Co and the single methyl acrylate (MA) unit insertion into the Me-Co and H-Co allows for the in situ formation of Co-C(COOMe) bonds as an initiator for OMRP of MA, (2) the migratory insertion of ethylene into Co-C(COOMe) bonds leads to the formation of an alkyl-Co species as active species for CIP of ethylene, and (3) MA insertion to the alkyl-Co to regenerate a Co-C(COOMe) bond. The architectures of copolymers were confirmed by various nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA)/differential scanning calorimetry (DSC), and size-exclusion chromatography (SEC) analyses.

Gray matter structures associated with neuroticism: A meta-analysis of whole-brain voxel-based morphometry studies.

Neuroticism is major higher-order personality trait and has been robustly associated with mental and physical health outcomes. Although a growing body of studies have identified neurostructural markers of neuroticism, the results remained highly inconsistent. To characterize robust associations between neuroticism and variations in gray matter (GM) structures, the present meta-analysis investigated the concurrence across voxel-based morphometry (VBM) studies using the anisotropic effect size signed differential mapping (AES-SDM). A total of 13 studies comprising 2,278 healthy subjects (1,275 females, 29.20 ± 14.17 years old) were included. Our analysis revealed that neuroticism was consistently associated with the GM structure of a cluster spanning the bilateral dorsal anterior cingulate cortex and extending to the adjacent medial prefrontal cortex (dACC/mPFC). Meta-regression analyses indicated that the neuroticism-GM associations were not confounded by age and gender. Overall, our study is the first whole-brain meta-analysis exploring the brain structural correlates of neuroticism, and the findings may have implications for the intervention of high-neuroticism individuals, who are at risk of mental disorders, by targeting the dACC/mPFC.

Brain gray matter structures associated with trait impulsivity: A systematic review and voxel-based meta-analysis.

Trait impulsivity is a multifaceted personality characteristic that contributes to maladaptive life outcomes. Although a growing body of neuroimaging studies have investigated the structural correlates of trait impulsivity, the findings remain highly inconsistent and heterogeneous. Herein, we performed a systematic review to depict an integrated delineation of gray matter (GM) substrates of trait impulsivity and a meta-analysis to examine concurrence across previous whole-brain voxel-based morphometry studies. The systematic review summarized the diverse findings in GM morphometry in the past literature, and the quantitative meta-analysis revealed impulsivity-related volumetric GM alterations in prefrontal, temporal, and parietal cortices. In addition, we identified the modulatory effects of age and gender in impulsivity-GM volume associations. The present study advances understanding of brain GM morphometry features underlying trait impulsivity. The findings may have practical implications in the clinical diagnosis of and intervention for impulsivity-related disorders.

Which Staging System Is More Suitable for Gastric Neuroendocrine Cancer and Mixed Adenoneuroendocrine Carcinomas? A Multicenter Cohort Study.

PURPOSE: To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). METHODS: Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. RESULTS: Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. CONCLUSIONS: Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

Multi-institutional development and validation of a nomogram to predict recurrence after curative resection of gastric neuroendocrine/mixed adenoneuroendocrine carcinoma.

OBJECTIVE: To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma [(MA)NEC]. BACKGROUND: Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse. METHODS: A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG). RESULTS: The median follow-up time was 40 months (1-169 months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%, p < 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%). CONCLUSIONS: Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.

Impact of intrauterine hypoxia on adolescent and adult cognitive function in rat offspring: sexual differences and the effects of spermidine intervention.

Intrauterine hypoxia (IUH) affects the growth and development of offspring. It remains unclear that how long the impact of IUH on cognitive function lasts and whether sexual differences exist. Spermidine (SPD) has shown to improve cognition, but its effect on the cognitive function of IUH offspring remains unknown. In the present study we investigated the influence of IUH on body weight and neurological, motor and cognitive function and the expression of APP, BACE1 and Tau5 proteins in brain tissues in 2- and 4-month-old IUH rat offspring, as well as the effects of SPD intervention on these parameters. IUH rat model was established by treating pregnant rats with intermittent hypoxia on gestational days 15-21, meanwhile pregnant rats were administered SPD (5 mg·kg-1·d-1;ip) for 7 days. Neurological deficits were assessed in the Longa scoring test; motor and cognitive functions were evaluated in coat hanger test and active avoidance test, respectively. We found that IUH decreased the body weight of rats in both sexes but merely impaired motor and cognitive function in female rats without changing neurological function in the rat offspring of either sex at 2 months of age. For 4-month-old offspring, IUH decreased body weight in males and impaired neurological function and increased cognitive function in both sexes. IUH did not affect APP, BACE1 or Tau5 protein expression in either the hippocampus or cortex of all offspring; however, it increased the cortical Tau5 level in 2-month-old female offspring. Surprisingly, SPD intervention prevented weight loss. SPD intervention reversed the motor and cognitive decline caused by IUH in 2-month-old female rat offspring. Taken together, IUH-induced cognitive decline in rat offspring is sex-dependent during puberty and can be recovered in adult rats. SPD intervention improves IUH-induced cognitive and neural function decline.