Development and validation of a scale to measure the care needs of Crohn's disease patients: a mixed-methods study.

BACKGROUND: Crohn's disease (CD) patients require varying levels of supportive care. In order to facilitate caregivers and nurses in precisely evaluating the caregiving requirements of these patients, we developed the CD-specific Care Needs Scale (CD-CNS). METHODS: This study employed a mixed-methods approach, integrating qualitative and quantitative methodologies. The initial items of the scale were developed through qualitative interviews, Delphi expert consultation, and literature review, while the final items were refined through clinical testing. Qualitative interviews were conducted based on the supportive care needs framework and Maslow's hierarchy of needs, and scale items were constructed through a literature search and qualitative interviews. The initial version of the scale with 45 items was obtained after the items were verified and modified by expert consultation. A total of 250 CD patients admitted to the gastroenterology department of a hospital in China were selected for verification of the initial version of the scale. A self-designed general questionnaire was used to obtain patients' medical history and sociodemographic data, and the Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) was used as the criterion. Exploratory factor analysis (EFA) was performed on the CD-CNS to evaluate the dimensions, factor structure, reliability, criterion validity, and construct validity. RESULTS: EFA identified 5 dimensions and retained 27 items with strong internal consistency reliability (α = 0.940). The Cronbach's α coefficients for each dimension ranged from 0.824 to 0.921. Criterion validity was assessed using Spearman's coefficient, which demonstrated a significant correlation with the IBDQ (P < 0.050). The test-retest reliability for each dimension after two weeks ranged from 0.655 to 0.895. CONCLUSIONS: We developed and validated a new scale that can be used to assess the care needs of CD patients. This new tool can guide the specific supportive care of CD patients. TRIAL REGISTRATION: This study was reviewed and approved by the Ethics Committee of the Second Hospital of Nanjing (2021-LS-ky-022). The study was duly registered and approved online through the Trial Center of the Second Hospital of Nanjing in 2021. Confidentiality was ensured by anonymizing all the data. The entire study process was conducted under the supervision of the Ethics Committee of Nanjing Second Hospital. Informed consent was obtained from the patients, and each patient volunteered and agreed to participate.

Multi-omic analysis tools for microbial metabolites prediction.

How to resolve the metabolic dark matter of microorganisms has long been a challenging problem in discovering active molecules. Diverse omics tools have been developed to guide the discovery and characterization of various microbial metabolites, which make it gradually possible to predict the overall metabolites for individual strains. The combinations of multi-omic analysis tools effectively compensates for the shortcomings of current studies that focus only on single omics or a broad class of metabolites. In this review, we systematically update, categorize and sort out different analysis tools for microbial metabolites prediction in the last five years to appeal for the multi-omic combination on the understanding of the metabolic nature of microbes. First, we provide the general survey on different updated prediction databases, webservers, or software that based on genomics, transcriptomics, proteomics, and metabolomics, respectively. Then, we discuss the essentiality on the integration of multi-omics data to predict metabolites of different microbial strains and communities, as well as stressing the combination of other techniques, such as systems biology methods and data-driven algorithms. Finally, we identify key challenges and trends in developing multi-omic analysis tools for more comprehensive prediction on diverse microbial metabolites that contribute to human health and disease treatment.

Analysis of the prevalence and clinical features of respiratory syncytial virus infection in a pediatric hospital in Zhejiang Province from 2019 to 2023.

The aim of this study was to investigate the epidemiological characteristics of respiratory syncytial virus (RSV) infections in children in Zhejiang from 2019 to 2023. Data from pediatric patients who visited the Children's Hospital of Zhejiang University School of Medicine for RSV infection between 2019 and 2023 were analyzed. Nasopharyngeal swabs were collected for RSV antigen detection, and relevant patient information was collected. Factors such as age were analyzed. A total of 673 094 specimens were included from 2019 to 2023, with a rate of positive specimens of 4.74% (31 929/673 094). The highest rate of positive specimens of 10.82%, was recorded in 2021, while the remaining years had a rate of approximately 3%-5%. In terms of seasonal prevalence characteristics, the rate of positive specimens in 2019, 2020, and 2022 peaked in the winter months at approximately 8% and decreased in the summer months, where the rate of positive specimens remained at approximately 0.5%. In contrast, summer is the peak period for RSV incidence in 2021 and 2023, with the rate of positive specimens being as high as 9%-12%. Based on the prevalence characteristics of gender and age, this study found that the detection rate of positive specimens was higher in boys than in girls in 2019-2023. In 2019-2022, among the different age groups, the highest rate of positive specimens was found in children aged 0 to <6 months, and it decreased with age. In 2023, the rate of positive specimens was above 8% in the 0 to <6 months, 6 to <12 months, and 1-2 years age groups, with the highest rate of positive specimens in the 1-2 years age group, and a gradual decrease in the rate of positive specimens with age for children over 3 years of age. Between 2019 and 2023, the epidemiological pattern of RSV changed. A summer peak was observed in 2021 and 2023.

Deciphering and designing microbial communities by genome-scale metabolic modelling.

Microbial communities are shaped by the complex interactions among organisms and the environment. Genome-scale metabolic models (GEMs) can provide deeper insights into the complexity and ecological properties of various microbial communities, revealing their intricate interactions. Many researchers have modified GEMs for the microbial communities based on specific needs. Thus, GEMs need to be comprehensively summarized to better understand the trends in their development. In this review, we summarized the key developments in deciphering and designing microbial communities using different GEMs. A timeline of selected highlights in GEMs indicated that this area is evolving from the single-strain level to the microbial community level. Then, we outlined a framework for constructing GEMs of microbial communities. We also summarized the models and resources of static and dynamic community-level GEMs. We focused on the role of external environmental and intracellular resources in shaping the assembly of microbial communities. Finally, we discussed the key challenges and future directions of GEMs, focusing on the integration of GEMs with quorum sensing mechanisms, microbial ecology interactions, machine learning algorithms, and automatic modeling, all of which contribute to consortia-based applications in different fields.

Seven Tesla Evidence for Columnar and Rostral-Caudal Organization of the Human Periaqueductal Gray Response in the Absence of Threat: A Working Memory Study.

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high-field 7 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals-yet, the present task posed only the most minimal (if any) "threat," with the cognitive tasks used being approximately as challenging as remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice.

Purpose: Alcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38ß, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer. Methods: Female adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined. Results: Alcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population. Conclusion: PFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Epidemiological and genetic characteristics of norovirus in Hangzhou, China, in the postepidemic era.

OBJECTIVE: Norovirus (NoV) is an important human pathogen that can cause severe gastroenteritis in vulnerable populations. This study aimed to analyze the epidemiological and genetic characteristics of 2021-2023 NoV in Hangzhou, China. METHODS: This study enrolled patients aged 0-18 years who underwent NoV RNA detection in the hospital between January 2021 and October 2023 and analyzed the epidemiological characteristics of NoV. Polymerase chain reaction (PCR) was used to detect NoV RNA. Subtype classification and whole-genome sequencing were performed. RESULTS: There was a high prevalence of NoV infection in 2023, with NoV-positive samples accounting for 63.10 % of the total number of positive samples collected during the three-year period. The prevalence was abnormally high in summer, and the number of positive samples accounted for 48.20 % of the total positive samples for the whole year, which was much greater than the level in the same period in previous years (2023, 48.20% vs 2021, 13.66% vs 2022, 15.21 %). The GⅡ.4 subtype played a leading role, followed by increased mixed infection with GⅠ.5 and GⅡ.4. Whole-genome sequencing results suggested that GII.P16-GⅡ.4 had R297H and D372N key locus mutations. The evolutionary rate was 4.29 × 10-3 for the RdRp gene and 4.84 × 10-3 for the VP1 gene. The RdRp gene and VP1 gene of NoV GII.P16-GⅡ.4 have undergone rapid population evolution during the COVID-19 epidemic. CONCLUSION: In the summer of 2023, an abnormally high incidence of NoV appeared in Hangzhou, China. The major epidemic strain GII.P16-GⅡ.4 showed a certain range of gene mutations and a fast evolutionary rate.

Analysis of current situation and influencing factors of marital adjustment in patients with Crohn's disease and their spouses.

The purpose of this study was to investigate the marital adjustment of patients with Crohn's disease and their spouses, and to analyze its influencing factors. It lays the investigation foundation for the follow-up binary study of Crohn's disease patients and their spouses. Using convenience sampling, 177 pairs of patients and their spouses from a tertiary hospital in Nanjing, China were selected. With face-to-face electronic questionnaires to survey the patient and spouse, the contents include the Lock-Wollance Marriage Adjustment Test, Subjective Well-Being Scale for Chinese Citizens, Couple Support Questionnaire, and Distress Self-Disclosure Scale. The marital adjustment score of patients was (99.03 ±â€…24.25), and the marital adjustment score of spouses was (99.61 ±â€…25.39). The proportions of patients with marital disorders and their spouses with marital disorders were 52.5% and 46.9%, respectively. Multiple linear regression showed that the spouse's age, family monthly income, time of diagnosis of Crohn's, distress self-disclosure, marital support, and subjective well-being were important factors influencing the marital adjustment of patients. Self-disclosure of spousal distress, marital support, age, and subjective well-being were important factors that influenced spouses' marital adjustment. Most couples with Crohn's disease have marital disorders, and their marital adjustment affects each other. However, the assessment results of one partner should not be limited to replacing those of the couple. In clinical practice, patient age, monthly family income, self-disclosure of distress, marital support, and subjective well-being should be considered. Spouses should be encouraged to participate in patient care and patient-spouse interventions should be implemented as a whole to improve marital stability.

The effect of nonpharmaceutical interventions on influenza virus transmission.

Background: The use of nonpharmaceutical interventions (NPIs) during severe acute respiratory syndrome 2019 (COVID-19) outbreaks may influence the spread of influenza viruses. This study aimed to evaluate the impact of NPIs against SARS-CoV-2 on the epidemiological features of the influenza season in China. Methods: We conducted a retrospective observational study analyzing influenza monitoring data obtained from the China National Influenza Center between 2011 and 2023. We compared the changes in influenza-positive patients in the pre-COVID-19 epidemic, during the COVID-19 epidemic, and post-COVID-19 epidemic phases to evaluate the effect of NPIs on influenza virus transmission. Results: NPIs targeting COVID-19 significantly suppressed influenza activity in China from 2019 to 2022. In the seventh week after the implementation of the NPIs, the number of influenza-positive patients decreased by 97.46% in southern regions of China and 90.31% in northern regions of China. However, the lifting of these policies in December 2022 led to an unprecedented surge in influenza-positive cases in autumn and winter from 2022 to 2023. The percentage of positive influenza cases increased by 206.41% (p < 0.001), with high positivity rates reported in both the northern and southern regions of China. Conclusion: Our findings suggest that NPIs against SARS-CoV-2 are effective at controlling influenza epidemics but may compromise individuals' immunity to the virus.

A state-of-the-art review on biomass-derived carbon materials for supercapacitor applications: From precursor selection to design optimization.

Biomass-derived carbon materials have the characteristics of a wide range of precursor sources, controllable carbon nano-dimension, large specific surface area and abundant heteroatoms doping. At present, biomass-derived carbon materials have been widely used in electrochemical energy storage devices, especially the research and development of biomass-derived carbon materials for supercapacitors has become mature and in-depth. Therefore, it is of importance to summarize the advanced technologies and strategies for optimizing biomass-derived carbon materials for supercapacitors, which will effectively promote the further development of high-performance supercapacitors. In this review, the recent research progress of biomass-derived carbon materials is provided in detail, including the selection of biomass precursors, the design of carbon nano-dimension and the theory of heteroatom doping. Besides, the preparation methods of biomass-derived carbon materials and the related processes of optimizing the electrochemical performance are also summarized. This review ends with the perspectives for future research directions and challenges in the field of biomass-derived carbon materials for electrochemical applications. This review aims to provide helpful reference information for the nano-dimensional design and electrochemical performance optimization of biomass-derived carbon materials for the practical application of supercapacitors.

Escherichia coli Infection Sepsis: An Analysis of Specifically Expressed Genes and Clinical Indicators.

Since E. coli is the most prevalent sepsis bacterium, studying its pathogenic molecular pathways may help with its early diagnosis and individualized treatment. However, few studies have investigated the molecular characterization of E. coli infection only. We extracted E. coli infection-specific genes and indicators from published data and clinical laboratory results in this study. GSE65088 showed 277, 377, and 408 DEGs for E. coli and other bacteria, E. coli and healthy groups, and other bacteria and healthy groups, respectively. DEGs, the MEgreen module with the highest relevance in WGCNA, and the first three MCODE subnetworks were used to find E. coli infection-specific hub genes. HSPA1B and TNF were verified in GSE6269 with ROC-AUCs of 0.7038 and 0.7116, respectively. CIBERSORT showed increased B-cell naive and T-cell CD4 naive infiltration in E. coli infectious sepsis. Patients infected with E. coli were younger than those infected with other pathogens. Compared to the other bacterially infectious sepsis patients, the E. coli patients had low globulin, prealbumin, creatine kinase, and high bilirubin levels. The clinically significant difference indicator IL-2, in combination with hub genes, better differentiated the healthy and E. coli groups, with an ROC-AUC of 0.8793. The study suggested that HSPA1B and TNF may be E.-coli-infection-specific genes, which may help explain the molecular mechanism of infectious sepsis.

The role of microbial interactions in dental caries: Dental plaque microbiota analysis.

OBJECTIVES: Dental caries is a result of the ecological dysfunction of the polymicrobial community on the tooth surface, which evolves through microbial interactions. In this study, we conducted a thorough analysis of the dental plaque microbiome to comprehend its multi-microbial aetiology. MATERIALS AND METHOD: In this study, plaque was collected from healthy tooth surfaces, shallow carious teeth and deep carious teeth, and bacterial composition and abundance were assessed using 16S rRNA high-throughput sequencing. Random forest and LEfSe were used to profile various microorganisms at each stage. Additionally, we developed a molecular ecological network (MEN) based on random matrix theory (RMT) to examine microbial interactions for the first time. RESULTS: Our results reveal that Scardovia wiggsiae, Streptococcus mutans, and Propionibacterium acidifaciens may be associated with initial caries, and Propionibacterium acidifaciens differentiates between shallow and deep caries. As caries progressed, the alpha diversity index declined, indicating a decrease in microbial variety. The network topological indices such as centralization betweenness revealed that the caries network had become more complex, involving more microbial interactions. The shallow network revealed a high negative correlation ratio across nodes, indicating that microbes competed heavily. In contrast, the positive correlation ratio of deep network nodes was high, and microorganisms transitioned from a competitive to a synergistic state. CONCLUSIONS: This study suggests that microbial diversity and interactions are critical to caries progression and that future caries research should give greater consideration to the role of microbial interaction factors in caries progression.

LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Therapeutic options for advanced HCC are limited, which is due to a lack of full understanding of pathogenesis. Cellular senescence is a state of cell cycle arrest, which plays important roles in the pathogenesis of HCC. Mechanisms underlying hepatocellular senescence are not fully understood. LncRNA NEAT1 acts as an oncogene and contributes to the development of HCC. Whether NEAT1 modulates hepatocellular senescence in HCC is unknown. METHODS: The role of NEAT1 and KIF11 in cellular senescence and tumor growth in HCC was assessed both in vitro and in vivo. RNA pulldown, mass spectrometry, Chromatin immunoprecipitation (ChIP), luciferase reporter assays, RNA FISH and immunofluorescence (IF) staining were used to explore the detailed molecular mechanism of NEAT1 and KIF11 in cellular senescence of HCC. RESULTS: We found that NEAT1 was upregulated in tumor tissues and hepatoma cells, which negatively correlated with a senescence biomarker CDKN2A encoding p16INK4a and p14ARF proteins. NEAT1 was reduced in senescent hepatoma cells induced by doxorubicin (DOXO) or serum starvation. Furthermore, NEAT1 deficiency caused senescence in cultured hepatoma cells, and protected against the progression of HCC in a mouse model. During senescence, NEAT1 translocated into cytosol and interacted with a motor protein KIF11, resulting in KIF11 protein degradation and subsequent increased expression of CDKN2A in cultured hepatoma cells. Furthermore, KIF11 knockdown caused senescence in cultured hepatoma cells. Genetic deletion of Kif11 in hepatocytes inhibited the development of HCC in a mouse model. CONCLUSIONS: Conclusively, NEAT1 overexpression reduces senescence and promotes tumor progression in HCC tissues and hepatoma cells, whereas NEAT1 deficiency causes senescence and inhibits tumor progression in HCC. This is associated with KIF11-dependent repression of CDKN2A. These findings lay the foundation to develop potential therapies for HCC by inhibiting NEAT1 and KIF11 or inducing senescence.

Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain: replication and extension with 7 Tesla fMRI.

The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, a process called allostasis. In support of allostasis, the brain continually models the internal state of the body, a process called interoception. Using published tract-tracing studies in non-human animals as a guide, we previously identified a large-scale system supporting allostasis and interoception in the human brain with functional magnetic resonance imaging (fMRI) at 3 Tesla. In the present study, we replicated and extended this system in humans using 7 Tesla fMRI (N = 91), improving the precision of subgenual and pregenual anterior cingulate topography as well as brainstem nuclei mapping. We verified over 90% of the anatomical connections in the hypothesized allostatic-interoceptive system observed in non-human animal research. We also identified functional connectivity hubs verified in tract-tracing studies but not previously detected using 3 Tesla fMRI. Finally, we demonstrated that individuals with stronger fMRI connectivity between system hubs self-reported greater interoceptive awareness, building on construct validity evidence from our earlier paper. Taken together, these results strengthen evidence for the existence of a whole-brain system supporting interoception in the service of allostasis and we consider the implications for mental and physical health.

Risk factors for post-stroke depression in patients with mild and moderate strokes.

To determine the possible risk factors for post-stroke depression in patients with mild and moderate acute strokes. A cross-sectional descriptive study was conducted involving 129 patients with mild and moderate acute strokes. The patients were divided into post-stroke depression and non-depressed stroke groups according to the Hamilton Depression Rating Scale for Depression-17 item and Patient Health Questionnaire-9 item assessments. All participants were evaluated based on clinical characteristics and a battery of scales. Patients with post-stroke depression had an increased stroke frequency, severe stroke symptoms and poor performance in activities of daily living (ADL), cognitive function, sleep quality, interest in pleasurable activities, negative life events, and utilization of social support compared to stroke patients without depression. The Negative Life Event Scale (LES) score was significantly and independently associated with an increased probability of depression in stroke patients. Negative life events were shown to be independently associated with the incidence of depression in patients with mild and moderate acute strokes, likely mediating the influence of other predictors of depression, such as a history of stroke, decreased ADL ability, and utilization of support.

Nomogram for predicting hemodynamic instability and the association between preoperative 3D printing and hemodynamic instability during laparoscopic adrenalectomy for pheochromocytoma.

Laparoscopic adrenalectomy (LA) for resection of pheochromocytomas (PCCs) is associated with high risk of complications and morbidity due to intraoperative hemodynamic instability (HDI). This study aims to identify factors related to HDI during laparoscopic resection of pheochromocytoma and develop a scoring model for prediction of HDI. Data of a total of 119 patients with pathological confirmed PCCs were collected at a single center in China between 2010 and 2021. All patients underwent unilateral LA for PCCs. Clinical and biochemical variables were collected. Next-generation sequencing was performed in all PCCs patients for detection of mutations. Univariate and multivariable logistic regression analyses were used to select risk factors for constructing the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the discrimination of the nomogram. The calibration curve was performed. Finally, four variables including 24 h urinary output of urine vanillylmandelic acid (VMA) ≥ 58 µmol/day, tumor size ≥ 4 cm, right-side tumor location, Cluster 2 mutations were independent risk factors for HDI during LA and were included in the nomogram. The nomogram demonstrated a good discrimination performance with an AUC of 0.784 [95% confidence interval (CI), 0.701-0.867]. The calibration curve showed a bias-corrected AUC of 0.758. Multivariable analysis revealed that preoperative 3D printing is an independent protective factor for HDI. Our study proposed a novel nomogram for prediction of HDI during LA for resection of PCCs. Preoperative 3D printing was associated with HDI in PCCs.

Correspondence of functional connectivity gradients across human isocortex, cerebellum, and hippocampus.

Gradient mapping is an important technique to summarize high dimensional biological features as low dimensional manifold representations in exploring brain structure-function relationships at various levels of the cerebral cortex. While recent studies have characterized the major gradients of functional connectivity in several brain structures using this technique, very few have systematically examined the correspondence of such gradients across structures under a common systems-level framework. Using resting-state functional magnetic resonance imaging, here we show that the organizing principles of the isocortex, and those of the cerebellum and hippocampus in relation to the isocortex, can be described using two common functional gradients. We suggest that the similarity in functional connectivity gradients across these structures can be meaningfully interpreted within a common computational framework based on the principles of predictive processing. The present results, and the specific hypotheses that they suggest, represent an important step toward an integrative account of brain function.

PLAGL1 is associated with prognosis and cell proliferation in pancreatic adenocarcinoma.

BACKGROUND: Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. METHODS: We analyzed the expression levels of PLAG family genes in both The Cancer Genome Atlas (TCGA) database and a Gene Expression Omnibus (GEO) database, and confirmed the results in our three independent cohorts of 382 PAAD tissues and 362 adjacent nontumor pancreatic tissues. Integrated analyses were carried out to explore the function, mechanism and prognostic value of the selected PLAG family gene in PAAD patients. RESULTS: By analyzing the TCGA and GEO databases, PLAGL1 was identified to be downregulated in PAAD tissues, and its decreasing levels of both mRNA and protein were verified in our three independent PAAD cohorts. PLAGL1 expression was inversely correlated with clinicopathological factors including the Ki67+ cell rate and pathologic stage. Further GSEA of the TCGA-PAAD cohort demonstrated that multiple signaling pathways implicated in cell proliferation were enriched in the lower PLAGL1 expressing PAAD group. Moreover, we demonstrated that PLAGL1 expression was obviously negatively associated with patients' overall survival outcome in both the TCGA-PAAD cohort and our verification cohorts. Additionally, through MTS and BrdU assays, we further demonstrated in vitro that PLAGL1 had the impact of preventing the proliferation of pancreatic cancer cells. CONCLUSIONS: Our present study suggested that downregulated PLAGL1 might act as a biomarker in predicts poor prognosis and one of important factors in increasing cell proliferation in PAAD. This study provides us with a novel prognostic marker and therapeutic strategy for PAAD, which deserves further study.

Adolescent- and adult-initiated alcohol exposure in mice differentially promotes tumorigenesis and metastasis of breast cancer.

BACKGROUND: Alcohol exposure increases the risk of breast cancer. Alcohol consumption by adolescents is a serious social and public health issue. This study investigated the impact of adolescent alcohol consumption on mammary tumorigenesis and progression and compared it to that of adult alcohol exposure in animal models. METHODS: Female adolescent (5 weeks) and adult (8 weeks) MMTV-Wnt1 mice were exposed to alcohol either chronically or acutely. For chronic alcohol exposure, animals were fed a liquid diet containing 6.7% ethanol for 23 weeks. For acute exposure, animals were treated with ethanol (2.5 g/kg, 25% w/v) via intraperitoneal (IP) injection for 15 days. RESULTS: In control animals, the tumor latency was 18.5 to 22 weeks. Both chronic and acute alcohol exposure in adolescent mice significantly shortened the tumor latency to 9.5 and 8.4 weeks, respectively. However, adult-initiated alcohol exposure had little effect on the tumor latency. Both adolescent- and adult-initiated alcohol exposure significantly increased lung metastasis. Adolescent-initiated alcohol exposure but not adult-initiated alcohol exposure increased the breast cancer stem cell population. Adolescent-initiated alcohol exposure significantly altered the proliferation of mammary epithelial cells, ductal growth, and the formation of terminal end buds in the mammary glands. Adolescent-initiated alcohol exposure but not adult-initiated alcohol exposure increased estradiol levels in the blood. Acute adolescent alcohol exposure also significantly increased blood progesterone levels. Furthermore, adolescent-initiated alcohol exposure activated PAK1 and p38γ MAPK, critical regulators of mammary tumorigenesis and aggressiveness, respectively, while adult-initiated alcohol exposure activated only p38γ MAPK. In addition, both adolescent and adult alcohol exposure significantly decreased the levels of a prognostic marker miR200b. CONCLUSIONS: Adolescent-initiated alcohol exposure enhanced both tumorigenesis and aggressiveness of mammary tumors, while adult-initiated alcohol exposure mainly promoted tumor metastasis. Thus, adolescent mice were more sensitive than adult mice in response to alcohol-induced tumor promotion.