The Risk Factors of Postpartum Urinary Retention for Women by Vaginal Birth: A Systematic Review and Meta-Analysis.

INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention is one of the most common complications in women during the immediate postpartum period. The objective was to systematically assess risk factors for postpartum urinary retention after vaginal delivery. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we retrieved relevant studies from PubMed, Embase, Cochrane Library, Web of Science Core Collection, China National Knowledge Internet, Wangfang Database, and Chinese Biomedical Database for observational studies investigating the risk factors for postpartum urinary retention from inception to 11 November 2022. The Newcastle-Ottawa Scale and Joanna Briggs Institute's tool were used to assess the risk of bias. We conducted a meta-analysis using RevMan 5.3. RESULTS: In total, 3,074 articles were screened and data from 27 studies were used in the meta-analysis. Sixteen risk factors were identified, namely, labor augmentation (OR = 1.72, 95% CI = 1.17-2.51), primiparity (OR = 2.36, 95% CI = 1.64-3.38), manual fundal pressure (OR = 2.84, 95% CI = 1.00-8.11), perineal hematoma (OR = 7.28, 95% CI = 1.62-32.72), vulvar edema (OR = 7.99, 95% CI = 5.50-11.63), the total duration of labor (MD = 90.10, 95% CI = 49.11-131.08), the duration of the first stage of labor (MD = 33.97, 95% CI = 10.28-57.65), the duration of the second stage of labor (MD = 14.92, 95% CI = 11.79-18.05), the duration of the second stage of labor > 60 min (OR = 3.18, 95% CI = 1.32-7.67), mediolateral episiotomy (OR = 3.65, 95% CI = 1.70-7.83), severe perineal tear (OR = 3.21, 95% CI = 1.84-5.61), epidural analgesia (OR = 3.23, 95% CI = 1.50-6.96), forceps delivery (OR = 4.95, 95% CI = 2.88-8.51), vacuum delivery (OR = 2.44, 95% CI = 1.30-4.58), neonatal birth weight > 4,000 g (OR = 3.61, 95% CI = 1.96-6.65), and neonatal birth weight > 3,500 g (OR = 1.89, 95% CI = 1.12-3.19). CONCLUSIONS: Our results demonstrated that labor augmentation, primiparity, manual fundal pressure, perineal hematoma, vulvar edema, the total duration of labor, the duration of the first stage of labor, the duration of the second stage of labor, the duration of the second stage of labor > 60 min, mediolateral episiotomy, severe perineal tear, epidural analgesia, forceps delivery, vacuum delivery, and neonatal birth weight > 4,000 g and > 3,500 g were risk factors for postpartum urinary retention in women with vaginal delivery. The specific ranges of the first and the second stages of labor causing postpartum urinary retention need to be clarified.

Increased Small Ubiquitin-like Modifier-Activating Enzyme SAE1 Promotes Hepatocellular Carcinoma by Enhancing mTOR SUMOylation.

SUMOylation, one of the most important posttranslational modifications of proteins, plays an essential role in various biological processes; however, enzymes that control SUMOylation in hepatocellular carcinoma (HCC) are still unclear. Comprehensive exploration of the expression and clinical significance of SUMO enzymes in HCC would be of great value. Here, we obtained the gene expression profile of each small ubiquitin-like modifier (SUMO) protein and the corresponding clinical information from The Cancer Genome Atlas. We found that all SUMO enzymes were significantly increased in HCC tissues compared with that in adjacent nontumorous tissues. We identified a 6-gene prognostic signature, including SAE1, PIAS2, PIAS3, SENP3, SENP5, and UBC9, that could effectively predict the overall survival in patients with HCC. Specifically, SAE1 was the most valuable prognostic indicator. In 282 clinical samples, we found that SAE1 was closely related to the clinicopathologic parameters and prognosis of patients with HCC. In vitro and in vivo studies showed that SAE1 knockdown inhibits the proliferation, migration, and invasion of HCC cells. Mechanistically, we confirmed that SAE1 plays a role in driving HCC progression, which is largely dependent on the SUMOylation of mTOR signaling. In conclusion, our study revealed that the expression of SUMO enzymes, especially SAE1, is highly associated with HCC development and acts as a promising prognostic predictor.

Hepatocyte-specific HDAC3 ablation promotes hepatocellular carcinoma in females by suppressing Foxa1/2.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common primary liver cancer, prevails mainly in males and has long been attributed to androgens and higher circumstantial levels of interleukin-6 (IL-6) produced by resident hepatic macrophages. METHODS: Constitutively hepatocyte-specific histone deacetylase 3 (HDAC3)-deficient (HDAC3LCKO) mice and constitutively hepatocyte-specific HDAC3 knockout and systemic IL-6 simultaneously ablated (HDAC3LCKO& IL-6-/-) mice were used in our study to explore the causes of sex differences in HCC. Additionally, we performed human HCC tissues with an IHC score. Correlation analysis and linear regression plots were constructed to reveal the association between HDAC3 and its candidate genes. To further elucidate that HDAC3 controls the expression of Foxa1/2, we knocked down HDAC3 in HUH7 liver cancer cells. RESULTS: We observed a contrary sex disparity, with an earlier onset and higher incidence of HCC in female mice when HDAC3 was selectively ablated in the liver. Loss of HDAC3 led to constant liver injury and the spontaneous development of HCC. Unlike the significant elevation of IL-6 in male mice at a very early age, female mice exhibit stable IL-6 levels, and IL-6 ablation did not eliminate the sex disparity in hepatocarcinogenesis in HDAC3-deficient mice. Oestrogen often protects the liver when combined with oestrogen receptor alpha (ERα); however, ovariectomy in HDAC3-ablated female mice significantly delayed tumourigenesis. The oestrogen-ERα axis can also play a role in tumour promotion in the absence of Foxa1 and Foxa2 in the receptor complex. Loss of HDAC3 profoundly reduced the expression of both Foxa1 and Foxa2 and impaired the binding between Foxa1/2 and ERα. Furthermore, a more frequent HDAC3 decrease accompanied by the simultaneous Foxa1/2 decline was found in female HCC compared to that in male HCC. CONCLUSION: In summary, we reported that loss of HDAC3 reduces Foxa1/2 and thus promotes HCC development in females in an oestrogen-dependent manner.

Resolving Charge Distribution for Compositionally Heterogeneous Battery Cathode Materials.

The isostructural nature of Li-layered cathodes allows for accommodating multiple transition metals (TMs). However, little is known about how the local TM stoichiometry influences the charging behavior of battery particles thus impacting battery performance. Here, we develop heterogeneous compositional distributions in polycrystalline LiNi1-x-yMnxCoyO2 (NMC) particles to investigate the interplay between local stoichiometry and charge distribution. These NMC particles exhibit a broad, continuous distribution of local Ni/Mn/Co stoichiometry, which does not compromise the global layeredness. The local Mn and Ni concentrations in individual NMC particles are positively and negatively correlated with the electrochemically induced Ni oxidation, respectively, whereas the Co concentration does not impose a clear effect on the Ni oxidation. The resulting material delivers excellent reversible capacity, rate capability, and cycle life at high operating voltages. Engineering Ni/Mn/Co distribution in NMC particles may provide a path toward controlling the charge distribution and thus chemomechanical properties of polycrystalline battery particles.

Melanocortin 5 receptor signaling pathway in health and disease.

Melanocortin hormone system plays a key role in maintaining the homeostasis of our body via their neuro-immune-endocrine activities and regulates a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The pathobiologic actions of all melanocortins are conveyed by melanocortin receptors. As the last melanocortin receptor to be cloned and characterized, melanocortin receptor 5 (MC5R) is widely expressed in both central nervous system and a number of peripheral organ systems in man. However, the exact effect of the MC5R mediated melanocortinergic signaling remains largely uncertain. Owing to the recent advances in developing highly selective peptidomimetic agonists and antagonists of MC5R and also to studies in MC5R knockout animals, our understanding of MC5R pathobiology has been greatly expanded and strengthened. Evidence suggests that MC5R plays a key role in governing immune reaction and inflammatory response, and is pivotal for the regulation of sexual behavior, thermoregulation, and exocrine secretion, like sebogenesis, lacrimal secretion and release of sex pheromones. As such, recent translational efforts have focused on developing novel sebum-suppressive therapies for seborrhoea and acne vulgaris based on antagonizing MC5R. Conversely, selective MC5R agonists have demonstrated promising beneficial effects in immune-mediated diseases, metabolic endocrinopathies and other disease conditions, such as glomerular diseases and dry eyes, skin and mouth. Thus, MC5R-mediated signaling is essential for health. Therapeutic targeting of MC5R represents a promising and pragmatic therapeutic strategy for diverse diseases. This review article delineates the biophysiology of MC5R-mediated biophysiology of the melanocortin hormone system, discusses the existing data on MC5R-targeted therapy in experimental disease models, and envisages the translational potential for treating human diseases.

Contemplation-action-maintenance model of behaviour change for persons with coronary heart disease: A qualitative study.

AIMS AND OBJECTIVES: To explore factors of health behaviour maintenance from the perspective of coronary heart disease (CHD) patients. BACKGROUND: The majority of CHD patients do not achieve appropriate theory-based intervention to maintain health behaviours. Previous health behaviour change theories give little importance to behaviour maintenance. DESIGN: A qualitative descriptive study. METHODS: Thirty CHD patients were recruited purposively and interviewed from four hospitals in Beijing, China, during January 2017-August 2019. Data were analysed using template analysis methods. The COREQ checklist was used. RESULTS: Perceived enjoyment and perceived effectiveness from the newly adopted behaviours emerged as vital factors for maintaining health behaviour; contemplation-action-maintenance (CAM) model to explain the behaviour change and maintenance of CHD patients was constructed. CONCLUSIONS: The CAM model provides insight into the factors of health behaviour action and maintenance among CHD patients. Professionals can develop interventions from the perspective of patients' experiences to promote maintenance of behaviour. RELEVANCE TO CLINICAL PRACTICE: Professionals need to consider that the goal of behavioural intervention should initially and continuously target patients' perseverance. Interventions of health behaviour that bring enjoyment may aid long-term maintenance. Also, healthcare providers can enhance patients' perception of effectiveness to motivate their behaviour maintenance in lifestyle change programmes.

Sonidegib, a Smoothened Inhibitor, Promotes Apoptosis and Suppresses Proliferation of Natural Killer/T-Cell Lymphoma.

BACKGROUND Dysregulation of the Hedgehog (Hh) pathway modulates various aspects of hematologic and solid tumors, but its effects in human Natural killer/T-cell lymphoma (NKTCL) are unclear. Moreover, no study has examined the consequences of pharmacologically inhibiting Hh signaling in NKTCL cell lines. MATERIAL AND METHODS In this study, the expression of Smoothened (Smo) and Glioma-associated oncogene 1 (Gli1) in NKTCL tissue were scrutinized. Two human NKTCL cell lines, SNK6 and SNT8, were subjected to various doses of sonidegib (a Smo inhibitor) and incubated for distinct durations. The cell apoptosis was examined by flow cytometry, CCK-8 assay was run to assess proliferation, and protein levels were quantified by Western blotting. RESULTS Both Smo and Gli1 expression were higher in NKTCL tissue than in Lymphoid Reactive Hyperplasia (LRH). Sonidegib significantly suppressed proliferation in NKTCL cells and the effect was dose-dependent. Further analysis revealed that sonidegib treatment elevated the number of apoptotic cells in a dose- and time-dependent manner. In addition, sonidegib downregulated Smo and Gli1expression in NKTCL cells. CONCLUSIONS The Hh pathway is crucial to the development of NKTCL and thus holds huge promise as a treatment for this disease.

Different Surgical Approaches to 313 Cesarean Scar Pregnancies.

STUDY OBJECTIVE: To evaluate the efficacy of different surgical treatments for cesarean scar pregnancy (CSP). DESIGN: Retrospective study (Canadian Task Force classification II-3). SETTING: Affiliated university hospitals. PATIENTS: Women (n = 313) with CSP. INTERVENTIONS: Dilation and curettage under ultrasound guidance (DCUS, n = 124), dilation and curettage with hysteroscopic guidance (DCH, n = 103), vaginal excision (n = 55), laparotomy (n = 12), and laparoscopy (n = 19). MEASUREMENTS AND MAIN RESULTS: Undetectable serum human chorionic gonadotropin (hCG) levels and thickness of the uterine scar were measured before and after surgery. Success rates of the 5 surgical treatments of CSP (DCUS, DCH, vaginal excision, laparotomy, and laparoscopy) ranged between 89% and 100%. Postoperative treatment was not needed in the vaginal and laparotomy groups, and vaginal treatment was associated with shorter operative time than laparotomy and laparoscopy and shorter time to undetectable hCG levels than DCUS and DCH. Serum hCG levels on day 3 after surgery were significantly lower than baseline levels in all groups of patients, but there was no significant difference between levels on days 3 and 5 postoperatively. Median scar thickness after surgery in the vaginal surgery, laparotomy, and laparoscopy groups was thicker than that in the DCUS and DCH groups. CONCLUSION: In certain circumstances, CSP can be treated simply by DCH or DCUS. However, time to undetectable hCG levels is prolonged compared with more invasive techniques.

Determining the motivations of family members to undertake cardiopulmonary resuscitation training through grounded theory.

AIMS: To explore the motivation of family members of patients at high risk for sudden cardiac death for undertaking cardiopulmonary resuscitation (CPR) training. BACKGROUND: Home cardiac arrests are associated with poor outcomes because few family members learn CPR. Little is known about factors that motivate family members to participate in CPR training. DESIGN: We used grounded theory to establish a theoretical framework to explore the motivational factors for learning CPR among family members. METHODS: Twelve participant observations and 42 semi-structured interviews with family members of different behaviours towards CPR training were conducted from December 2013 - November 2016. Data were analysed using constant-comparisons, situational analysis, and encoding. FINDINGS: A motivation-behaviour theoretical framework for learning CPR was constructed. We identified meeting inner needs as the core category to demonstrate motivation. Security motivation and responsibility motivation emerged as main categories, which demonstrate that seeking a sense of security and shouldering family responsibility were important considerations for family members to learn CPR. These two motivations produced high-engagement behaviours of family members to learn CPR. CONCLUSIONS: The motivations we identified-deriving from a sense of security and family responsibility-are the main reasons family members would learn CPR and, therefore, should be understood by medical professionals. Understanding these motivations may help in the formulation of customized CPR training that further meets the needs of family members. For example, motivational interventions that are integrated with a family-based CPR course can be designed to improve the participation of family members and the sustainability of the course.

Finding a Needle in the Haystack: Identification of Functionally Important Minority Phases in an Operating Battery.

The in-depth understanding of the minority phases' roles in functional materials, e.g., batteries, is critical for optimizing the system performance and the operational efficiency. Although the visualization of battery electrode under operating conditions has been demonstrated, the development of advanced data-mining approaches is still needed in order to identify minority phases and to understand their functionalities. The present study uses nanoscale X-ray spectromicroscopy to study a functional LiCoO2/Li battery pouch cell. The data-mining approaches developed herein were used to search through over 10 million X-ray absorption spectra that cover more than 100 active cathode particles. Two particles with unanticipated chemical fingerprints were identified and further analyzed, providing direct evidence and valuable insight into the undesired side reactions involving the cation dissolution and precipitation as well as the local overlithiation-caused subparticle domain deactivation. The data-mining approach described in this work is widely applicable to many other structurally complex and chemically heterogeneous systems, in which the secondary/minority phases could critically affect the overall performance of the system, well beyond battery research.

Continuous-scan capability at SSRL and applications to X-ray diffraction.

Typical X-ray diffraction measurements are made by moving a detector to discrete positions in space and then measuring the signal at each stationary position. This step-scanning method can be time-consuming, and may induce vibrations in the measurement system when the motors are accelerated and decelerated at each position. Furthermore, diffraction information between the data points may be missed unless a fine step-scanning is used, which further increases the total measurement time. To utilize beam time efficiently, the motor acceleration and deceleration time should be minimized, and the signal-to-noise ratio should be maximized. To accomplish this, an integrated continuous-scan system was developed at the Stanford Synchrotron Radiation Lightsource (SSRL). The continuous-scan system uses an in-house integrated motor controller system and counter/timer electronics. SPEC software is used to control both the hardware and data acquisition systems. The time efficiency and repeatability of the continuous-scan system were tested using X-ray diffraction from a ZnO powder and compared with the step-scan technique. Advantages and limitations of the continuous-scan system and a demonstration of variable-velocity continuous scan are discussed.

Bio-Sourced, High-Performance Carbon Fiber Reinforced Itaconic Acid-Based Epoxy Composites with High Hygrothermal Stability and Durability.

Thermosetting polymers and composites are a class of high-performance materials with significant industrial applications. However, the widespread use of thermosets and their composites generates large quantities of waste and leads to serious economic and environmental problems, there is a critical need in the elaboration of sustainable composite materials. Here, we propose a method to prepare sustainable carbon fiber reinforced composites with different degrees of greenness by blending environmentally friendly EIA with DGEBA in different ratios, and the properties compared with a well-known commercial petroleum-based epoxy resin. The prepared carbon fiber reinforced polymer (CFRP) composites with different degrees of greenness had excellent dimensional stability under extreme hygrothermal aging. After aging, the green CFRP composite T700/EIA-30 has higher strength and performance retention than that of petroleum-based CFRP composites. The higher hygrothermal stability and durability of EIA-based epoxy resins as compared with BPA-based epoxy resins demonstrated significant evidence to design and develop a novel bio-based epoxy resin with high performance to substitute the petroleum-based epoxy resin.

Associations of lifestyle with mental health and well-being in Chinese adults: a nationwide study.

Background: A healthy lifestyle is beneficial to individuals' health. However, little is known about the associations of lifestyle factors with mental health and well-being. This study examined the associations of lifestyle factors with mental health (i.e., depression, anxiety, loneliness, perceived pressure, and self-rated health status) and well-being in Chinese adults. Methods: A nationally representative survey was conducted in China from 20 June 2022 to 31 August 2022. Data from the survey were analyzed using multiple linear regression to determine the associations of lifestyle with mental health and well-being in Chinese adults. Standardized regression coefficients (ß) and 95% confidence intervals (CIs) were estimated using multiple linear regression. Results: The survey included 28,138 Chinese adults. Multiple linear regression results showed that there were significant negative associations of lifestyle scores with scores of depression (ß = -0.93, 95% CI: -0.98, -0.88), anxiety (ß = -0.71, 95% CI: -0.76, -0.67), loneliness (ß = -0.23, 95% CI: -0.24, -0.21), and perceived pressure (ß = -0.19, 95% CI: -0.22, -0.16). Moreover, there were significant positive associations of lifestyle with self-rated health status (ß = 1.99, 95% CI: 1.79, 2.20) and well-being (ß = 0.96, 95% CI: 0.91, 1.02). Conclusion: This study provides insight into the associations of lifestyle factors with mental health and well-being and highlights the importance of improving and maintaining healthy lifestyle behaviors for favorable mental health and well-being.

Ionic Liquids Facilitate the Dispersion of Branched Polyethylenimine Grafted ZIF-8 for Reinforced Epoxy Composites.

Metal-organic frameworks (MOFs) have been previously shown as an emerging modified class of epoxy resin. In this work, we report a simple strategy for preventing zeolitic imidazolate framework (ZIF-8) nanoparticles from agglomerating in epoxy resin (EP). Branched polyethylenimine grafted ZIF-8 in ionic liquid (BPEI-ZIF-8) nanofluid with good dispersion was prepared successfully using an ionic liquid as both the dispersant and curing agent. Results indicated that the thermogravimetric curve of the composite material had no noticeable change with increasing BPEI-ZIF-8/IL content. The glass transition temperature (Tg) of the epoxy composite was reduced with the addition of BPEI-ZIF-8/IL. The addition of 2 wt% BPEI-ZIF-8/IL into EP effectively improved the flexural strength to about 21.7%, and the inclusion of 0.5 wt% of BPEI-ZIF-8/IL EP composites increased the impact strength by about 83% compared to pure EP. The effect of adding BPEI-ZIF-8/IL on the Tg of epoxy resin was explored, and its toughening mechanism was analyzed in combination with SEM images showing fractures in the EP composites. Moreover, the damping and dielectric properties of the composites were improved by adding BPEI-ZIF-8/IL.

Effect of Strain Rate on Tensile Properties of Carbon Fiber-Reinforced Epoxy Laminates with Different Stacking Sequences and Ply Orientations.

In practical application situations, a carbon fiber-reinforced polymer (CFRP) is often subjected to complex dynamic loadings. The effect of the strain rate on mechanical properties is very important for the CFRP design and product development. In this work, static and dynamic tensile properties of CFRP with different stacking sequences and ply orientations were investigated. The results showed that the tensile strengths of CFRP laminates were sensitive to the strain rate, while Young's modulus was independent of the strain rate. Moreover, the strain rate effect was related to the stacking sequences and ply orientations. The experimental results showed that the strain rate effects of the cross-ply laminates and quasi-isotropic-ply laminates were lower than that of the unidirectional-ply laminates. Finally, the failure modes of CFRP laminates were investigated. Failure morphology demonstrated that the differences in strain rate effects among cross-ply laminates, quasi-isotropic-ply laminates, and unidirectional-ply laminates were caused by the mismatch between the fiber and the matrix when the strain rate increased.

Mechanical Properties of Weld Lines in Injection-Molded Carbon Fiber-Reinforced Nylon (PA-CF) Composites.

Weld lines are a common defect generated in injection molding, which apparently affects the performance of final products, but the available reports on carbon fiber-reinforced thermoplastics are still rather few. In this study, the effects of injection temperature, injection pressure, and fiber content on the mechanical properties of weld lines were studied for carbon fiber-reinforced nylon (PA-CF) composites. The weld line coefficient was also calculated by comparing specimens with and without weld lines. The tensile and flexural properties of PA-CF composites significantly increased with the rise of fiber content for specimens without weld lines, while injection temperature and pressure demonstrated slight influences on mechanical properties. However, the existence of weld lines had negative influences on the mechanical properties of PA-CF composites due to poor fiber orientation in weld line regions. The weld line coefficient of PA-CF composites decreased as fiber content increased, indicating that the damage of weld lines to mechanical properties increased. The microstructure analysis showed that there were a large number of fibers distributed vertically to flow direction in weld lines regions, which could not play a reinforcing role. In addition, increasing injection temperature and pressure facilitated fiber orientation, which improved the mechanical properties of composites with low fiber content, while weakening composites with high fiber content instead. This article provides practical information for product design containing weld lines, which helps to optimize the forming process and formula design of PA-CF composites with weld lines.

Synchronous Improvement of Mechanical and Damping Properties of Structural Damping Composites with Polyetherimide Non-Woven Fabric Interlayers Loaded with Polydopamine and Carbon Nanotubes.

Structural damping composites exhibit considerable potential in aerospace and other fields due to their excellent damping and vibration reduction performance, as well as their structural carrying capacity. However, conventional structural damping composite materials generally do not combine excellent mechanical and damping properties at the same time, which makes it difficult for them to meet the practical demand in engineering. In this paper, polyetherimide (PEI) non-woven fabric interlayer materials loaded with quantified polydopamine (PDA) and carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) were used to prepare carbon fiber-reinforced bismaleimide composites through the co-curing process. The mechanical and damping properties of the composites were systematically studied. The results demonstrate that PEI non-woven fabric interlayers loaded with PDA and MWCNTs-COOH can synchronously improve the mechanical and damping properties of the co-cured composites. The incorporation of carbon nanotubes and polydopamine during the co-curing process synergistically improves the flexural strength, flexural modulus, interlaminar shear strength, and impact fracture toughness of the composites. Most importantly, damping properties show an increase of 45.0% in the loss factor of the co-cured composites. Moreover, the reinforcement mechanism was investigated using the optical microscopy and scanning electron microscopy, which indicated that the PEI interlayers loaded with carbon nanotubes and polydopamine form a rich resin area between the layers of the composites.

Glutamine synthetase-negative hepatocellular carcinoma has better prognosis and response to sorafenib treatment after hepatectomy.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS: GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.

Repurchase intentions of new e-commerce users in the COVID-19 context: The mediation role of brand love.

The use of e-commerce has exploded due to the impact of COVID-19. People with no experience in e-commerce prior to the COVID-19 pandemic began online shopping for their safety following the pandemic outbreak. As such, these newly joined customers have played a vital role in the rapid development of e-commerce. Maintaining these customers and increasing their repurchase intention is a core issue for e-commerce platform companies. Thus, using new e-commerce users as the participants, this study investigated the structural relationship between brand experience, brand emotional factors (brand attachment and brand love), brand loyalty, and repurchase intention with brand love as the mediator. Research on the multidimensional brand experience (i.e., sensory, emotional, behavioral, and cognitive) from Chinese customers' perspective is still lacking, and our study attempts to fill this gap. A structured questionnaire and hypotheses were designed based on studies and survey of 310 respondents from China in this study. The study results show that, first, the four dimensions of brand experience have a significant positive correlation with brand emotion, with brand cognitive experience having the greatest impact on consumer brand emotion. Second, the influence of brand emotion on brand loyalty is positive and significant, and brand attachment has a stronger influence than brand love on brand loyalty. In addition, brand loyalty has a positive effect on repurchase intention. Finally, brand love plays a mediating role on the relationship between brand attachment and brand loyalty. To enhance customers' brand attachment and love for e-commerce platforms, companies must enhance customers' interest and curiosity in their products. And companies will improve their services to customers by introducing artificial intelligence algorithms to increase customers' repurchase intention, which will ultimately increasing their profitability. This study contributes to the development of e-commerce platform companies.

Loss of Numb promotes hepatic progenitor expansion and intrahepatic cholangiocarcinoma by enhancing Notch signaling.

Numb, a stem cell fate determinant, acts as a tumor suppressor and is closely related to a wide variety of malignancies. Intrahepatic cholangiocarcinoma (iCCA) originates from hepatic progenitors (HPCs); however, the role of Numb in HPC malignant transformation and iCCA development is still unclear. A retrospective cohort study indicated that Numb was frequently decreased in tumor tissues and suggests poor prognosis in iCCA patients. Consistently, in a chemically induced iCCA mouse model, Numb was downregulated in tumor cells compared to normal cholangiocytes. In diet-induced chronic liver injury mouse models, Numb ablation significantly promoted histological impairment, HPC expansion, and tumorigenesis. Similarly, Numb silencing in cultured iCCA cells enhanced cell spheroid growth, invasion, metastasis, and the expression of stem cell markers. Mechanistically, Numb was found to bind to the Notch intracellular domain (NICD), and Numb ablation promoted Notch signaling; this effect was reversed when Notch signaling was blocked by γ-secretase inhibitor treatment. Our results suggested that loss of Numb plays an important role in promoting HPC expansion, HPC malignant transformation, and, ultimately, iCCA development in chronically injured livers. Therapies targeting suppressed Numb are promising for the treatment of iCCA.