Single-trial interindividual correlation shows semantic and visuospatial networks are fundamental for advanced mathematical learning.

Mathematical learning and ability are crucial for individual and national economic and technological development, but the neural mechanisms underlying advanced mathematical learning remain unclear. The current study used functional magnetic resonance imaging (fMRI) to investigate how brain networks were involved in advanced mathematical learning and transfer. We recorded fMRI data from 24 undergraduate students as they learned the advanced mathematical concept of a commutative mathematical group. After learning, participants were required to complete learning and transfer behavioural tests. Results of single-trial interindividual brain-behaviour correlation analysis found that brain activity in the semantic and visuospatial networks, and the functional connectivity within the semantic network during advanced mathematical learning were positively correlated with learning and transfer effects. Additionally, the functional connectivity between the semantic and visuospatial networks was negatively correlated with the learning and transfer effects. These findings suggest that advanced mathematical learning relies on both semantic and visuospatial networks.

Much lower prevalence and mortality of chronic obstructive pulmonary disease in Japan than in the US despite higher smoking rates: A meta analysis/systematic review.

BACKGROUND: A recent systematic review showed Japan's mortality from chronic obstructive pulmonary disease (COPD) is the lowest among 204 countries, despite notably higher smoking rates in men in Japan than in the US. This study aims to compare (1) trends in smoking rates, (2) trends in COPD mortality, and (3) the spirometry-based COPD prevalence in the general adult population between Japan and the US. METHODS: Age- and sex-specific smoking rates from the 1980s through 2010s and COPD mortality from 1999 through 2019 were obtained from national surveys and official statistics (International Classification of Diseases-10th codes J40-44), respectively. A systematic review and meta-analysis was performed to estimate COPD prevalence in Japan, while the National Health and Nutrition Examination Survey 2007-2012 was used for the US. A fixed ratio of 0.7 of forced expiratory volume in the first second of forced vital capacity was used to define COPD. RESULTS: Over the past four decades, men in Japan consistently had 20-30% higher smoking rates than their US counterparts. From 1999-2019, age-adjusted COPD mortality in men in Japan was only a third of the US, whereas that in women was less than a tenth in 2019. Synthesizing data from 11 studies, involving 89,955 participants, Japan's COPD prevalence was more than 10% lower than in the US in almost all age groups for both sexes. CONCLUSIONS: This study showed markedly lower rates of COPD in Japan than in the US. Investigating factors contributing to the paradoxical observations could lead to advancing COPD risk reduction strategies.

Unveiling the hidden pathologies: preoperative endoscopic findings in patients with obesity undergoing bariatric surgery.

BACKGROUND: Obesity is closely associated with upper gastrointestinal disorders. The recommendations for routine preoperative esophagogastroduodenoscopy (EGD) before bariatric surgery remains a topic of debate. This study aimed to describe the pathological endoscopic findings in individuals qualified for bariatric surgery. METHODS: Retrospective analysis was conducted on preoperative gastroscopy reports of patients who underwent bariatric surgery at our hospital between October 2022 and October 2023. RESULTS: A total of 405 patients were included in the study. The two most prevalent endoscopic findings during EGD in this patient cohort were chronic superficial gastritis (326/405, 80.5%) and reflux esophagitis (82/405, 20.2%). Some patients exhibited two or more abnormalities. Patients with reflux esophagitis were older, had a higher proportion of men, higher BMI, higher rates of smoking and drinking compared to those without it (P = 0.033, P < 0.001, P = 0.003, P = 0.001, and P = 0.003, respectively). Morbid obesity (P = 0.037), smoking habits (P = 0.012), and H. pylori infection (P = 0.023) were significant risk factors for reflux esophagitis in male patients, while age (P = 0.007) was the sole risk factor in female patients. No statistically significant differences were observed in surgical procedures between LA-A and B groups (P = 0.382), but statistically significant differences were noted between the nondiabetic and diabetic groups (P < 0.001). CONCLUSIONS: Preoperative EGD can unveil a broad spectrum of pathologies in patients with obesity, suggesting the need for routine examination before bariatric surgery. The findings of this study can guide bariatric surgeons in developing tailored treatments and procedures, thus significantly enhancing prognosis. Gastroscopy should be performed routinely in Chinese patients planning to undergo bariatric surgery.

Self-Reported Eating-Occasion Frequency and Timing are Reproducible and Relatively Valid in the American Cancer Society Cancer Prevention Study-3 Diet Assessment Substudy.

BACKGROUND: Accurate assessment of eating-occasion behaviors, such as timing, frequency, and consumption intervals, is important for evaluating associations with obesity and other chronic diseases. OBJECTIVES: The main objective of this study was to assess the relative validity of a 24-hour grid approach to assess eating-occasion timing and frequency in comparison to data derived from repeated 24-hour dietary recalls (DRs). A second objective was to assess the 1-year test-retest reproducibility of the 24-hour grid. METHODS: Between 2015 and 2016, 626 participants in the Cancer Prevention Study-3 (CPS-3) Diet Assessment Substudy (mean age, 52 years; age range, 31-70 years; 64% female; 64% non-Hispanic white, 22% non-Hispanic black, 14% Hispanic) completed 2 grids and up to 6 unannounced, telephone, interviewer-administered DRs over 1 year. Spearman correlations (ρ; 95% CIs) were calculated to assess reproducibility between the repeated eating-occasion grid-derived variables (e.g., numbers of snacks and meals per day, timing of eating occasions) and to assess relative validity by comparing the meal grid and DR-derived summary data separately for weekdays and weekend days. RESULTS: Reproducibility correlations for eating-occasion variables derived from the eating-occasion grids completed 1 year apart were ≥0.5 for the majority of variables analyzed for both weekdays and weekend days, including numbers of snacks and meals per day and timing of the first and last eating occasions of the day. Relative validity was highest among weekday variables and was ≥0.5 for the majority of variables, with correlations ranging from ρ values of 0.32 (number of meals per day) to 0.68 (hour of the first eating occasion). CONCLUSIONS: These findings suggest the eating-occasion grid used in CPS-3 has good reproducibility over 1 year and yields estimates comparable to those from a more detailed method of assessment of eating timing and frequency.

Metabolic and bariatric surgery in China: A summary of the Greater China Metabolic and Bariatric Surgery Database and comparison with other international registry databases.

AIMS: To summarize the Greater China Metabolic and Bariatric Surgery Database (GC-MBD) and to compare patient characteristics and different procedures performed with data from published reports from other international bariatric surgery registries. MATERIALS AND METHODS: Data were extracted from the GC-MBD registry in 2021. Baseline demographic characteristics, obesity-related comorbidities and operational information were analysed. Descriptive comparisons of these data were made with the published reports from four other international/national databases, including the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) registry, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database of the United States, the National Bariatric Surgical Registry (NBSR) of the United Kingdom, and the Scandinavian Obesity Surgery Registry (SOReg). RESULTS: Fifty-three centres in China registered 6807 cases in the GC-MBD. Compared with published data from the IFSO registry, MBSAQIP, NBSR and SOReg, patients in China undergoing surgery were younger and had a lower body mass index. The incidence of other obesity-related comorbidities, except for gastroesophageal reflux disease, was also higher than in Western countries. Furthermore, more patients underwent sleeve gastrectomy, less revisional bariatric surgery was reported in China, and jejunojejunal bypass with sleeve gastrectomy, uncommon in other countries, was China's second-leading bariatric procedure. CONCLUSIONS: By establishing comprehensive national registries such as the GC-MBD, real-world information can be gathered on clinical practice and patient outcomes. Insights into variations in clinical practice can be identified by comparing reports from different countries, which can help in making and evaluating healthcare policies on the best clinical practices at a national level.

High-definition transcranial direct current stimulation (HD-tDCS) of the left middle temporal gyrus (LMTG) improves mathematical reasoning.

The role of the visuospatial network in mathematical processing has been established, but the role of the semantic neural network in mathematical processing is still poorly understood. The current study used high-definition transcranial direct current stimulation (HD-tDCS) to examine whether the semantic network supports mathematical processing. Using a single-blind, randomized, sham-controlled experimental design, 48 participants were randomly assigned to receive either anodal or sham HD-tDCS on the left middle temporal gyrus (LMTG), a core region of the semantic network. A number series completion task was used to measure mathematical reasoning and an arithmetical computation task was used as a control condition. Both tasks were administered before and after the 20 min HD-tDCS. The results showed that anodal HD-tDCS on the LMTG enhanced performance on the number series completion task, but not on the arithmetical computation task. Trial-level analysis further showed greater improvement at the more difficult problems of the number series completion task. These results demonstrate that the semantic network plays an important role in mathematical processing.

[Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components].

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

RBP-J deficiency promoted the proliferation and differentiation of CD133-positive cells in both in vitro and in vivo studies.

Although Notch signalling pathway could control the proliferation and differentiation of neural stem cells (NSCs), it is largely unknown about the effect of Notch signalling pathway on the neurogenesis of CD133-positive cells. By using the primary cultured ependymal cells and the transgenic mouse, we found that CD133 immunoreactivity was exclusively localized in the ependymal layer of ventricles; moreover, most CD133-positive cells were co-labelled with Nestin. In addition, recombination signal binding protein J (RBP-J), a key nuclear effector of Notch signalling pathway, was highly active in CD133-positive cells. CD133-positive cells can differentiate into the immature and mature neurons; in particular, the number of CD133-positive cells differentiating into the immature and mature neurons was significantly increased following the deficiency or interference of RBP-J in vivo or in vitro. By using real-time qPCR and Western blot, we found that RBP-J and Hes1 were downregulated, whereas Notch1 was upregulated in the expression levels of mRNAs and proteins following the deficiency or interference of RBP-J. These results demonstrated RBP-J deficiency promoted the proliferation and differentiation of CD133-positive cells. Therefore, we speculated that RBP-J could maintain CD133-positive cells in the characteristics of NSCs possibly by regulating Notch1/RBP-J/Hes1 pathway. It will provide a novel molecular insight into the function of RBP-J as well as facilitate a future investigation of CD133-positive cells with respect to their potential application in neurodegenerative disorder.

Algebra dissociates from arithmetic in the brain semantic network.

BACKGROUND: Mathematical expressions mainly include arithmetic (such as 8 - (1 + 3)) and algebra (such as a - (b + c)). Previous studies have shown that both algebraic processing and arithmetic involved the bilateral parietal brain regions. Although previous studies have revealed that algebra was dissociated from arithmetic, the neural bases of the dissociation between algebraic processing and arithmetic is still unclear. The present study uses functional magnetic resonance imaging (fMRI) to identify the specific brain networks for algebraic and arithmetic processing. METHODS: Using fMRI, this study scanned 30 undergraduates and directly compared the brain activation during algebra and arithmetic. Brain activations, single-trial (item-wise) interindividual correlation and mean-trial interindividual correlation related to algebra processing were compared with those related to arithmetic. The functional connectivity was analyzed by a seed-based region of interest (ROI)-to-ROI analysis. RESULTS: Brain activation analyses showed that algebra elicited greater activation in the angular gyrus and arithmetic elicited greater activation in the bilateral supplementary motor area, left insula, and left inferior parietal lobule. Interindividual single-trial brain-behavior correlation revealed significant brain-behavior correlations in the semantic network, including the middle temporal gyri, inferior frontal gyri, dorsomedial prefrontal cortices, and left angular gyrus, for algebra. For arithmetic, the significant brain-behavior correlations were located in the phonological network, including the precentral gyrus and supplementary motor area, and in the visuospatial network, including the bilateral superior parietal lobules. For algebra, significant positive functional connectivity was observed between the visuospatial network and semantic network, whereas for arithmetic, significant positive functional connectivity was observed only between the visuospatial network and phonological network. CONCLUSION: These findings suggest that algebra relies on the semantic network and conversely, arithmetic relies on the phonological and visuospatial networks.

Mathematics Meets Science in the Brain.

Mathematics and science are highly integrated disciplines, but the brain association between mathematics and science remains unclear. The current study used functional magnetic resonance imaging (fMRI) scans of 34 undergraduates (17 males, mean age = 20.3±1.64 years old) while they completed mathematical, physical and chemical principles, arithmetic computation, and sentence comprehension. We examined neural activation level, neural activation pattern, and neural connectivity to investigate the neural associations between mathematics and science (including physics and chemistry). The results showed that mathematical, physical, and chemical principles elicited similar neural activation level and neural activation pattern in the visuospatial network (mainly in the middle frontal gyrus and inferior parietal lobule), which were different from those elicited by sentence comprehension; those three principles also elicited similar neural activation level and neural activation pattern in the semantic network (mainly in the middle temporal gyrus, angular gyrus, inferior frontal gyrus, and dorsomedial prefrontal cortex), in contrast to that elicited by arithmetic computation. Effective connectivity analyses showed stronger connectivity between the middle temporal gyrus and inferior parietal lobule for mathematical, physical, and chemical principles than for sentence comprehension. The results suggest that visuospatial and semantic networks were critical for processing both mathematics and science.

Air Pollution and Weather Conditions Are Associated with Daily Outpatient Visits of Atopic Dermatitis in Shanghai, China.

BACKGROUND: Non-optimum weather conditions and air pollution have the potential to increase the risk of atopic dermatitis (AD), but the associations are rarely evaluated, especially in developing countries. OBJECTIVE: To investigate the independent influence and interaction effects of meteorological factors and air pollutants on the onset of AD. METHODS: Daily data on outpatient visits of AD were obtained from Shanghai Dermatology Hospital and comprised 34,633 patients during the period from January 2013 to December 2018. Meteorological conditions and air pollutant concentrations in Shanghai, China, during the 6-year period were collected. We applied the overdispersed generalized additive model and the distributed lag model to explore the short-term cumulative effects of environmental factors on AD. RESULTS: AD symptoms were aggravated by extreme low temperature (1st percentile, 0.5°C) (RR = 1.32, 95% CI: 1.16-1.51) and per 10 unit decrease of humidity (RR = 1.10, 95% CI: 1.12-2.47). The increased concentration of air pollutants except ozone (O3) contributed to the increased risk of AD outpatients. A 10 µg/m3 increase in sulfur dioxide (SO2) and nitrogen dioxide (NO2) were associated with 6.03% (95% CI: 2.29%, 9.91%), and 1.96% (95% CI: 0.46%, 3.48%) increase of AD outpatients. AD patients in the 8- to 17-year-old group were most susceptible to extreme low temperature, and patients in the 0- to 7-year-old group were most susceptible to air pollutants, including particulate matter (PM10), SO2, and NO2. Men were more sensitive to the effects of extreme low temperature than women, while women were more vulnerable to air pollutants. The adverse effects of SO2 and NO2 on AD can be enhanced significantly by the warm season or other pollutants. CONCLUSION: Exposure to a lower temperature, lower humidity, and higher levels of air pollutants is significantly associated with increased risks of AD incidence. These impacts were more pronounced in children less than 7 years old, women, and warm seasons.

Comparison of reader agreement, correlation with liver biopsy, and time-burden sampling strategies for liver proton density fat fraction measured using magnetic resonance imaging in patients with obesity: a secondary cross-sectional study.

BACKGROUND: The magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) has become popular for quantifying liver fat content. However, the variability of the region-of-interest (ROI) sampling strategy may result in a lack of standardisation of this technology. In an effort to establish an accurate and effective PDFF measurement scheme, this study assessed the pathological correlation, the reader agreement, and time-burden of different sampling strategies with variable ROI size, location, and number. METHODS: Six-echo spoiled gradient-recalled-echo magnitude-based fat quantification was performed for 50 patients with obesity, using a 3.0-T MRI scanner. Two readers used different ROI sampling strategies to measure liver PDFF, three times. Intra-reader and inter-reader agreement was evaluated using intra-class correlation coefficients and Bland‒Altman analysis. Pearson correlations were used to assess the correlation between PDFFs and liver biopsy. Time-burden was recorded. RESULTS: For pathological correlations, the correlations for the strategy of using three large ROIs in Couinaud segment 3 (S3 3L-ROI) were significantly greater than those for all sampling strategies at the whole-liver level (P < 0.05). For inter-reader agreement, the sampling strategies at the segmental level for S3 3L-ROI and using three large ROIs in Couinaud segment 6 (S6 3L-ROI) and the sampling strategies at the whole-liver level for three small ROIs per Couinaud segment (27S-ROI), one large ROI per Couinaud segment (9L-ROI), and three large ROIs per Couinaud segment (27S-ROI) had limits of agreement (LOA) < 1.5%. For intra-reader agreement, the sampling strategies at the whole-liver level for 27S-ROI, 9L-ROI, and 27L-ROI had both intraclass coefficients > 0.995 and LOAs < 1.5%. The change in the time-burden was the largest (100.80 s) when 9L-ROI was changed to 27L-ROI. CONCLUSIONS: For hepatic PDFF measurement without liver puncture biopsy as the gold standard, and for general hepatic PDFF assessment, 9L-ROI sampling strategy at the whole-liver level should be used preferentially. For hepatic PDFF with liver puncture biopsy as the gold standard, 3L-ROI sampling strategy at the puncture site segment is recommended.

Nurses' strengths use and turnover intention: The roles of job crafting and self-efficacy.

AIMS: Based on conservation of resources theory, the study aimed to investigate how nurses' strengths use affects their turnover intention and its potential mechanisms and boundary conditions. DESIGN: The study adopted a time-lagged research design. METHODS: The study was conducted from October 2019 to January 2020, with a sample of 234 registered nurses in a tertiary hospital in Beijing, China. The study used bootstrapping to test the hypotheses. RESULTS: Strengths use had a significant negative effect on turnover intention, and job crafting completely mediated the relationship between strengths use and turnover intention. Furthermore, self-efficacy positively moderated the direct relationship between strengths use and job crafting and the indirect relationship between strengths use and turnover intention via job crafting. CONCLUSION: The study is the first to examine the relationships among nurses' strengths use and turnover intention, demonstrating that the activation and accumulation of work resources through job crafting can effectively reduce nurses' turnover intention. Additionally, by emphasizing the moderating effect of self-efficacy, the study contributes to finding a way for hospitals to enhance the effectiveness of nurses' strengths use in terms of increased job crafting and reduced turnover intention. IMPACT: Nurse managers should help nurses identify their strengths to improve their strengths use, provide nurses with more freedom to craft their jobs and take actions to build nurses' self-efficacy and positive expectations about their jobs.

Brush Conformation of Polyethylene Glycol Determines the Stealth Effect of Nanocarriers in the Low Protein Adsorption Regime.

For nanocarriers with low protein affinity, we show that the interaction of nanocarriers with cells is mainly affected by the density, the molecular weight, and the conformation of polyethylene glycol (PEG) chains bound to the nanocarrier surface. We achieve a reduction of nonspecific uptake of ovalbumin nanocarriers by dendritic cells using densely packed PEG chains with a "brush" conformation instead of the collapsed "mushroom" conformation. We also control to a minor extent the dysopsonin adsorption by tailoring the conformation of attached PEG on the nanocarriers. The brush conformation of PEG leads to a stealth behavior of the nanocarriers with inhibited uptake by phagocytic cells, which is a prerequisite for successful in vivo translation of nanomedicine to achieve long blood circulation and targeted delivery. We can clearly correlate the brush conformation of PEG with inhibited phagocytic uptake of the nanocarriers. This study shows that, in addition to the surface's chemistry, the conformation of polymers controls cellular interactions of the nanocarriers.

Potential Protective Mechanisms of S-equol, a Metabolite of Soy Isoflavone by the Gut Microbiome, on Cognitive Decline and Dementia.

S-equol, a metabolite of soy isoflavone daidzein transformed by the gut microbiome, is the most biologically potent among all soy isoflavones and their metabolites. Soy isoflavones are phytoestrogens and exert their actions through estrogen receptor-ß. Epidemiological studies in East Asia, where soy isoflavones are regularly consumed, show that dietary isoflavone intake is inversely associated with cognitive decline and dementia; however, randomized controlled trials of soy isoflavones in Western countries did not generally show their cognitive benefit. The discrepant results may be attributed to S-equol production capability; after consuming soy isoflavones, 40-70% of East Asians produce S-equol, whereas 20-30% of Westerners do. Recent observational and clinical studies in Japan show that S-equol but not soy isoflavones is inversely associated with multiple vascular pathologies, contributing to cognitive impairment and dementia, including arterial stiffness and white matter lesion volume. S-equol has better permeability to the blood-brain barrier than soy isoflavones, although their affinity to estrogen receptor-ß is similar. S-equol is also the most potent antioxidant among all known soy isoflavones. Although S-equol is available as a dietary supplement, no long-term trials in humans have examined the effect of S-equol supplementation on arterial stiffness, cerebrovascular disease, cognitive decline, or dementia.

A novel multi-model fusion framework diagnoses the complex variation characteristics of ecological indicators and quantitatively reveals their driving mechanism.

Systematic analysis of the change law and driving mechanism of ecological indicators (GPP, ET, WUE), as well as the study of maximum threshold of water resources benefit changing with ecological benefit, are important prerequisites for realizing the scientific allocation and efficient utilization of water resources in desert riparian forests. However, previous studies have defects in the detailed description of the change characteristics of ecological indicators. How to accurately diagnose the characteristics of a site, mutation year, pattern (linear, exponential, logarithmic, etc.), duration of change, future change trends of ecological indicators in a desert riparian environment, as well as quantitatively revealing their driving mechanisms, are major scientific problems that need to be solved urgently. In this regard, an ensemble function coupling a logistic function and an asymmetric Gaussian function was creatively adopted, a novel framework was created to integrate the time-series trajectory fitting method and the sensitivity analysis method, and the arid and ecologically fragile Tarim River Basin was taken as a typical area. The results showed that with enhanced water resource management in the Tarim River Basin, GPP, ET, and WUE all showed patterns of increasing change and could be expected to continue to rise or to remain at a high-level stable state. The longest continuous period of GPP change was 15 years, showing that ecological restoration is a long-term process. The years of GPP mutation were consistent with the implementation periods of major measures in the Tarim River Basin (1990, 2001, and 2011), indicating the reliability of this framework. More importantly, when GPP increased to 216.44 gCm-2, the maximum WUE threshold of 0.93 gCm-2mm-1 occurred. This threshold can be used as a reference criterion for efficient utilization of ecological water in the basin. Among the ecological indicators studied, GPP was the most sensitive to environmental change, but GPP, with 80.60% of pixel area, showed a weak memory effect（α < 0.4). Besides, GPP was the most sensitive to the leaf area index (LAI) and had the strongest correlation with it (p < 0.001). Therefore, LAI can be used as the main control factor for judging plant growth. This research can provide important scientific guidance and reference for the analysis of ecological indicator changes and the sustainable utilization of water resources in arid areas.

Hierarchical integrated processing of reward-related regions in obese males: A graph-theoretical-based study.

Abnormal activities in reward-related regions are associated with overeating or obesity. Preliminary studies have shown that changes in neural activity in obesity include not only regional reward regions abnormalities but also impairments in the communication between reward-related regions and multiple functional areas. A recent study has shown that the transitions between different neural networks are nonrandom and hierarchical, and that activation of particular brain networks is more likely to occur after other brain networks. The aims of this study were to investigate the key nodes of reward-related regions in obese males and explore the hierarchical integrated processing of key nodes. Twenty-four obese males and 24 normal-weight male controls of similar ages were recruited. The fMRI data were acquired using 3.0 T MRI. The fMRI data preprocessing was performed in DPABI and SPM 12. Degree centrality analyses were conducted using GRETNA toolkit, and Granger causality analyses were calculated using DynamicBC toolbox. Decreased degree centrality was observed in left ventral medial prefrontal cortex (vmPFC) and right parahippocampal/hippocampal gyrus in group with obesity. The group with obesity demonstrated increased effective connectivity between left vmPFC and several regions (left inferior temporal gyrus, left supplementary motor area, right insular cortex, right postcentral gyrus, right paracentral lobule and bilateral fusiform gyrus). Increased effective connectivity was observed between right parahippocampal/hippocampal gyrus and left precentral/postcentral gyrus. Decreased effective connectivity was found between right parahippocampal/hippocampal gyrus and left inferior parietal lobule. This study identified the features of hierarchical interactions between the key reward nodes and multiple function networks. These findings may provide more evidence for the existing view of hierarchical organization in reward processing.

A new technique for treating hiatal hernia with gastroesophageal reflux disease: the laparoscopic total left-side surgical approach.

INTRODUCTION: Although the traditional bilateral surgical approach to treat hiatal hernia (HH) with gastroesophageal reflux disease (GERD) can provide local protection of the vagus nerve, the integrity of the entire vagus nerve cannot be evaluated. Therefore, we developed and described the total left-side surgical approach (TLSA), which theoretically reduces injury to the vagus nerve, and described the detailed surgical procedure. METHODS: Initially, we performed a cadaver study to explore the characteristics of the vagus nerve. Then, we prospectively evaluated the TLSA in 5 patients with HH and GERD between June 2020 and September 2020. Demographic characteristics, surgical parameters, perioperative outcomes, and follow-up findings were analyzed. RESULTS: The TLSA was successfully used in five patients (40-64 years old), and no major complications were noted. The median total operative time was 114 min, median blood loss was 50 mL, and median postoperative hospital stay was 3.8 days. Gastrointestinal function recovered within 4 days of surgery in all the patients. The 6-month follow-up gastroscopy examination showed well-established gastroesophageal flap valves. Compared with the baseline results, the 6-month follow-up results showed lower values for the total GerdQ score (12.4 vs. 6.2) and the total esophageal acid exposure time (3.48% vs. 0.38%). Based on the European Organization for Research and Treatment of Cancer quality of life questionnaire-stomach module 52 results, the incidence of dysphagia and flatulence decreased over time after the TLSA. CONCLUSIONS: The TLSA provides a clear and broad surgical field, less trauma, and rapid recovery; moreover, it is technically simple. Although our results suggest that the TLSA provides safety and short-term efficacy and is feasible for patients with HH and GERD, long-term results from a larger clinical trial are needed to validate these findings. Trial registration ChiCTR2000034028, registration date is June 21, 2020. The study was registered prospectively.

Bariatric surgery for non-alcoholic fatty liver disease in individuals with obesity (Base-NAFLD): protocol of a prospective multicenter observational follow-up study.

BACKGROUND: Bariatric surgery may be indicated in patients with nonalcoholic fatty liver disease (NAFLD) to achieve and maintain the degree of weight loss required to ensure therapeutic effects. However, bariatric surgery is still underrecognized in the treatment of NAFLD, including its inflammatory subtype, nonalcoholic steatohepatitis (NASH). Moreover, there is a lack of follow-up outcome data on different types of bariatric surgery in patients with NAFLD. This study aims to adequately assess the effect of bariatric surgery on NAFLD remission in obese patients. METHODS: This prospective multicentre observational follow-up study will include 142 obese patients with NAFLD scheduled to undergo one of the following surgical procedures: sleeve gastrostomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass. The primary outcome is the complete remission rate of NAFLD one year postoperatively, which is defined by liver fat fraction < 5% on magnetic resonance imaging; the secondary outcomes includes (i) changes in NASH and liver fibrosis biopsy findings, (ii) changes in body weight and abdominal adipose weight, (iii) resolution of obesity-related comorbidities, and (iv) incidence of adverse events. A long-term follow-up related to this study will also be conducted. DISCUSSION: This study will provide a necessary and preliminary foundation for the early identification and targeted treatment of patients with NAFLD who can be referred for bariatric surgery, as indicated for management of obesity and metabolic disease. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04366999. Registered 21 April 2020. ( https://clinicaltrials.gov/ct2/show/NCT04366999 ).

Sesquiterpene Lactone Deoxyelephantopin Isolated from Elephantopus scaber and Its Derivative DETD-35 Suppress BRAFV600E Mutant Melanoma Lung Metastasis in Mice.

Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis; therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5IF4g/Luc BRAFV600E mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5IF4g/Luc melanoma growth in vitro and in a xenograft mouse model. DET and DETD-35 treatment inhibited A375LM5IF4g/Luc cell proliferation, and induced G2/M cell-cycle arrest and apoptosis. Furthermore, A375LM5IF4g/Luc exhibited clonogenic, metastatic and invasive abilities, and several A375LM5IF4g/Luc metastasis markers, N-cadherin, MMP2, vimentin and integrin α4 were significantly suppressed by treatment with either compound. Interestingly, DET- and DETD-35-induced Reactive Oxygen Species (ROS) generation and glutathione (GSH) depletion were found to be upstream events important for the in vitro activities, because exogenous GSH supplementation blunted DET and DETD-35 effects on A375LM5IF4g/Luc cells. DET and DETD-35 also induced mitochondrial DNA mutation, superoxide production, mitochondrial bioenergetics dysfunction, and mitochondrial protein deregulation. Most importantly, DET and DETD-35 inhibited lung metastasis of A375LM5IF4g/Luc in NOD/SCID mice through inhibiting pulmonary vascular permeability and melanoma cell (Mel-A+) proliferation, angiogenesis (VEGF+, CD31+) and EMT (N-cadherin) in the tumor microenvironment in the lungs. These findings indicate that DET and DETD-35 may be useful in the intervention of lung metastatic BRAFV600E mutant melanoma.