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PURPOSE: This study aimed to explore the correlation between hemoglobin levels and albuminuria in US adults. METHODS: This cross-sectional investigation analyzed the National Health and Nutrition Examination Survey (NHANES) information from 2011 to 2020. Data on hemoglobin, albuminuria, and other variables were collected from all participants. The logistic-regression analyses and smoothed curves were used to substantiate the research objectives. RESULTS: The average age of the 8,868 participants was 49.5 ± 17.3 years, and 49.3% were men. The prevalence of albuminuria was 12.1%. After adjusting for potential variables in the logistic-regression analysis models, hemoglobin (per 1 g/dL increase) was inversely associated with the presence of albuminuria (odds ratio [OR], 0.92; 95% confidence interval [95%CI], 0.87-0.97). Compared with participants in quartile 3 (Q3, 14.1-15.0 g/dL) for hemoglobin levels, those in the lowest quartile 1 (Q1, 6.1-13.0 g/dL) and highest quartile 4 (Q4, 15.1-19.6 g/dL) had adjusted ORs for albuminuria of 1.48 (95% CI, 1.19-1.85) and 1.11 (95% CI, 0.9-1.38), respectively. Our observations indicated a U-shaped association between hemoglobin levels and albuminuria, with a point of inflection at approximately 15.5 g/dL. The effect sizes and CIs below and above this point were 0.853 (95% CI, 0.798-0.912) and 1.377 (95% CI, 1.055-1.797), respectively. CONCLUSION: This study indicates that the presence of albuminuria is linked to both low and high hemoglobin levels in US adults. The management of hemoglobin may benefit kidney health.

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Hematopoietic stem cells (HSCs) maintain homeostasis in the hematopoietic ecosystem, which is tightly regulated at multiple layers. Acute myeloid leukemia (AML) is a severe hematologic malignancy driven by genetic and epigenetic changes that lead to the transformation of leukemia stem cells (LSCs). Since somatic mutations in DNA methylation-related genes frequently occur in AML, DNA methylation is widely altered and functions as a starting engine for initiating AML. Additionally, RNA modifications, especially N6-methyladenosine (m6A), also play an important role in the generation and maintenance of the hematopoietic ecosystem, and AML development requires reprogramming of m6A modifications to facilitate cells with hallmarks of cancer. Given the complex pathogenesis and poor prognosis of AML, it is important to fully understand its pathogenesis. Here, we mainly focus on DNA methylation and RNA m6A modification in hematopoiesis and AML and summarize recent advances in this field.

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Background: Tracheo-carinal resection and reconstruction in cases of extensive malignant tumors present a significant surgical challenge, often complicated by high anastomotic tension and potential for incomplete anastomosis. Case Description: We report on a 45-year-old male with a primary adenoid cystic carcinoma. The tumor was about 3 cm in size and invaded about 1 cm of the lower trachea, 2 cm of the left main bronchus (LMB), and 1 cm of the right main bronchus (RMB), blocking about 70% of the tracheal lumen, 90% of the LMB, and 50% of the RMB. Resection of the lower trachea and part of the LMB and RMB was performed via the right chest. We used the right main bronchial flap as a bridge, suturing it separately to the lower tracheal segment and the LMB, thereby completing the carinal reconstruction. This technique was crucial for bridging the defect between the trachea and LMB, which was impossible to anastomose directly due to the tumor's extensive involvement. The elliptical-shaped lingual flap from the RMB provided a stable and tension-free foundation for the reconstruction, overcoming the limitations of conventional methods. Conclusions: The novel carinal reconstruction technique demonstrated a reliable alternative for complex tracheo-carinal defects, ensuring tension-free anastomosis and complete tumor resection with clear margins.

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INTRODUCTION AND IMPORTANCE: Fallopian tube cancer that is characterized only by inguinal lymph node metastasis without intra-abdominal widespread is rare. Here we report a patient with primary Fallopian tube cancer with bilateral inguinal metastases as the first symptom. CASE PRESENTATION: A 68-year-old patient with primary Fallopian tube cancer, with painless bilateral inguinal enlargement (7 × 6 cm on the right side, 3 × 2 cm on the left side) as the only manifestation, was confirmed by preoperative biopsy as metastatic high-grade serous denocarcinoma, consider the adnexal or peritoneal source. Pelvic MRI, abdominal CT and PET-CT showed irregular signal foci can be seen in the right adnexal area, with a maximum cross-section of about 7.5 × 7.0 × 4.0 cm, considering malignancy, ovarian cancer may be possible; bilateral pelvic wall, bilateral inguinal, right iliac vessels with hypermetabolic lymph nodes. Serum CA125 level was markedly elevated at 922.40 U/ml and HE4 at 394.50 pmol/L. No abnormality was found in gastrointestinal endoscopy. At exploratory laparotomy, the tumor was confined to the right rear of the uterus, and a solid tumor with a size of about 10 × 6 × 6 cm was seen. The surface was smooth and closely related to the uterus. There was almost no tumor spread in the pelvic abdominal cavity, but there was 50 ml of pale blood-colored peritoneal fluid. The right ovarian capsule was intact. Cytoreductive surgery was performed, postoperative pathology confirmed adenocarcinoma of the right fallopian tube, and the patient received six cycles of paclitaxel plus cisplatin combination chemotherapy were administered, with three 3-weeks intervals between cycles. And subsequent the patient participated in a clinical trial. The work has been reported in line with the SCARE criteria. CLINICAL DISCUSSION: Literature review indicates that inguinal lymph node as the first manifestation of fallopian tube cancer is not usual, and with no widespread lymphadenopathies and abdominopelvic cavity are even rarer. This case shows that rare cases with only inguinal lymph node metastasis may occur through the underlying lymphatic and/or hematogenous routes. CONCLUSION: The diagnosis of tubal cancer is sometimes complicated and delayed. For elderly women without nonspecific symptoms, especially those with obvious masses, detailed examinations, and imaging studies should be carried out in time. The treatment of tubal cancer is multi-modal. Due to the high risk of recurrence of fallopian tube cancer, the possibility of metastasis after the initial diagnosis is large, so it is very important to receive close and regular follow-up for patients with fallopian tube cancer after treatment. We suggest that more tumor centers study the possible mechanisms, metastasis patterns, biological characteristics, etc. of such patients, and at the same time efforts should be made to early differential diagnosis, and ultimately prolong the survival time of such patients.

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BACKGROUND: Intrapancreatic fat deposition (IPFD) exerts a significant negative impact on patients with type 2 diabetes mellitus (T2DM), accelerates disease deterioration, and may lead to impaired ß-cell quality and function. AIM: To investigate the correlation between T2DM remission and IPFD. METHODS: We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023, including 40 patients with weight loss-induced T2DM remission (research group) and 40 patients with short-term intensive insulin therapy-induced T2DM remission (control group). We comparatively analyzed improvements in IPFD [differential computed tomography (CT) values of the spleen and pancreas and average CT value of the pancreas]; levels of fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and insulin; and homeostasis model assessment of insulin resistance (HOMA-IR) scores. Correlation analysis was performed to explore the association between T2DM remission and IPFD. RESULTS: After treatment, the differential CT values of the spleen and pancreas, FBG, 2hPBG, and HOMA-IR in the research group were significantly lower than those before treatment and in the control group, and the average CT value of the pancreas and insulin levels were significantly higher. Correlation analysis revealed that the greater the T2DM remission, the lower the amount of IPFD. CONCLUSION: T2DM remission and IPFD are inversely correlated.

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Introduction: Dementia and physical disability are serious problems faced by the aging population, and their occurrence and development interact. Methods: Based on data from a national cohort of Chinese people aged 60 years and above from the China Health and Retirement Longitudinal Survey from 2011 to 2018, we applied the group-based trajectory model to identify the heterogeneous trajectories of cognitive function and physical disability in participants with different physical disability levels. Next, multinomial logistic regression models were used to explore the factors affecting these trajectories. Results: The cognitive function trajectories of the Chinese older people could be divided into three characteristic groups: those who maintained the highest baseline level of cognitive function, those with a moderate baseline cognitive function and dramatic progression, and those with the worst baseline cognitive function and rapid-slow-rapid progression. The disability trajectories also fell into three characteristic groups: a consistently low baseline disability level, a low initial disability level with rapid development, and a high baseline disability level with rapid development. Compared with those free of physical disability at baseline, a greater proportion of participants who had physical disability at baseline experienced rapid cognitive deterioration. Education, income, type of medical insurance, gender, and marital status were instrumental in the progression of disability and cognitive decline in the participants. Discussion: We suggest that the Chinese government, focusing on the central and western regions and rural areas, should develop education for the older people and increase their level of economic security to slow the rate of cognitive decline and disability among this age group. These could become important measures to cope with population aging.

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Hematopoietic homeostasis is maintained by hematopoietic stem cells (HSCs), and it is tightly controlled at multiple levels to sustain the self-renewal capacity and differentiation potential of HSCs. Dysregulation of self-renewal and differentiation of HSCs leads to the development of hematologic diseases, including acute myeloid leukemia (AML). Thus, understanding the underlying mechanisms of HSC maintenance and the development of hematologic malignancies is one of the fundamental scientific endeavors in stem cell biology. N  6-methyladenosine (m6A) is a common modification in mammalian messenger RNAs (mRNAs) and plays important roles in various biological processes. In this study, we performed a comparative analysis of the dynamics of the RNA m6A methylome of hematopoietic stem and progenitor cells (HSPCs) and leukemia-initiating cells (LICs) in AML. We found that RNA m6A modification regulates the transformation of long-term HSCs into short-term HSCs and determines the lineage commitment of HSCs. Interestingly, m6A modification leads to reprogramming that promotes cellular transformation during AML development, and LIC-specific m6A targets are recognized by different m6A readers. Moreover, the very long chain fatty acid transporter ATP-binding cassette subfamily D member 2 (ABCD2) is a key factor that promotes AML development, and deletion of ABCD2 damages clonogenic ability, inhibits proliferation, and promotes apoptosis of human leukemia cells. This study provides a comprehensive understanding of the role of m6A in regulating cell state transition in normal hematopoiesis and leukemogenesis, and identifies ABCD2 as a key factor in AML development.

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G protein pathway suppressor 2 (GPS2) has been shown to play a pivotal role in human and mouse definitive erythropoiesis in an EKLF-dependent manner. However, whether GPS2 affects human primitive erythropoiesis is still unknown. This study demonstrated that GPS2 positively regulates erythroid differentiation in K562 cells, which have a primitive erythroid phenotype. Overexpression of GPS2 promoted hemin-induced hemoglobin synthesis in K562 cells as assessed by the increased percentage of benzidine-positive cells and the deeper red coloration of the cell pellets. In contrast, knockdown of GPS2 inhibited hemin-induced erythroid differentiation of K562 cells. GPS2 overexpression also enhanced erythroid differentiation of K562 cells induced by cytosine arabinoside (Ara-C). GPS2 induced hemoglobin synthesis by increasing the expression of globin and ALAS2 genes, either under steady state or upon hemin treatment. Promotion of erythroid differentiation of K562 cells by GPS2 mainly relies on NCOR1, as knockdown of NCOR1 or lack of the NCOR1-binding domain of GPS2 potently diminished the promotive effect. Thus, our study revealed a previously unknown role of GPS2 in regulating human primitive erythropoiesis in K562 cells.

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Objective: Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis. Methods: We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome (n = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results. Results: According to the inverse variance-weighted estimation, we identified that ten bacterial traits (Class Actinobacteria, Class Bacteroidia, family Bifidobacteriaceae, family Rikenellaceae, genus Lachnospiraceae (UCG004 group), genus Ruminococcaceae (UCG013 group), order Bacteroidales, order Bifidobacteriales, genus Peptococcus and genus Victivallis) were negatively correlated with skin fibrosis while five bacterial traits (genus Olsenella, genus Oscillospira, genus Turicibacter, genus Lachnospiraceae (NK4A136group), and genus Sellimonas) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis. Objective conclusion: There is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.

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Objective: Despite the developments of in vitro fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure. Methods: We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I2 index was analyzed. Results: We identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I2 = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I2 = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I2 = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I2 = 24%], but not on LBR. In addition, >150µg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I2 = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I2 = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I2 = 22%], while ≤150µg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I2 = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I2 = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I2 = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection. Conclusion: G-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.

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The study aimed to evaluate the association between high-altitude polycythemia and hypertension in adults residing on Anduo County's plateau, which is located 4700 meters above sea level. A total of 387 individuals participated in the cross-sectional survey conducted between April and May of 2021. Interviews, physical inspections, and laboratory tests were employed to gather information about all of the subjects. The association between high-altitude polycythemia and hypertension was assessed using multivariable logistic regression models. The average age of the 387 participants was 32.6 ± 6.3 years. Of these participants, 260 (67%) were male. The overall prevalence of hypertension was 27.1% (57/380). When stratified by gender, the prevalence was 12.6% (16/127) in females and 34.2% (89/260) in males. The overall prevalence of high-altitude polycythemia was 19.6% (76/387). When stratified by gender, the prevalence was 26.2% (68/260) in males and 6.3% (8/127) in females. During logistic regression analysis, we found that participants with elevated hemoglobin per 10 g/L had a 26% greater risk of hypertension (adjusting for odds ratio [OR], 1.26; 95% confidence interval [CI], 1.11-1.44). Additionally, high-altitude polycythemia greatly increased the risk of hypertension in comparison to non-high-altitude polycythemia (OR, 3.01; 95% CI, 1.66-5.44, P < 0.001). The consistency of the results was further demonstrated by stratified and interaction analyses, showing that Hans individuals had a higher risk of hypertension. High-altitude polycythemia is positively associated with hypertension in adults residing at Tibetan ultrahigh altitudes. The results of the investigation may aid in the planning of future research and guide the development of targeted healthcare practices for high-altitude populations, particularly among Han Chinese residents of the Tibetan Plateau.

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OBJECTIVE: Although low-dose computed tomography has been proven effective to reduce lung cancer-specific mortality, a considerable proportion of surgically resected high-risk lung nodules were still confirmed pathologically benign. There is an unmet need of a novel method for malignancy classification in lung nodules. METHODS: We recruited 307 patients with high-risk lung nodules who underwent curative surgery, and 247 and 60 cases were pathologically confirmed malignant and benign lung lesions, respectively. Plasma samples from each patient were collected before surgery and performed low-depth (5×) whole-genome sequencing. We extracted cell-free DNA characteristics and determined radiomic features. We built models to classify the malignancy using our data and further validated models with 2 independent lung nodule cohorts. RESULTS: Our models using one type of profile were able to distinguish lung cancer and benign lung nodules at an area under the curve metrics of 0.69 to 0.91 in the study cohort. Integrating all the 5 base models using cell-free DNA profiles, the cell-free DNA-based ensemble model achieved an area under the curve of 0.95 (95% CI, 0.92-0.97) in the study cohort and 0.98 (95% CI, 0.96-1.00) in the validation cohort. At a specificity of 95.0%, the sensitivity reached 80.0% in the study cohort. With the same threshold, the specificity and sensitivity had similar performances in both validation cohorts. Furthermore, the performance of area under the curve reached 0.97 in both the study and validation cohorts when considering the radiomic profile. CONCLUSIONS: The cell-free DNA profiles-based method is an efficient noninvasive tool to distinguish malignancies and high-risk but pathologically benign lung nodules.

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Zinc oxide (ZnO) is a widely employed material for enhancing the performance of cellulose-based triboelectric nanogenerators (C-TENGs). Our study provides a novel chemical interpretation for the improved output efficiency of ZnO in C-TENGs. C-TENGs exhibit excellent flexibility and integration, achieving a maximum open-circuit voltage (Voc) of 210 V. The peak power density is 54.4 µW/cm2 with a load resistance of 107 Ω, enabling the direct powering of 191 light-emitting diodes with the generated electrical output. Moreover, when deployed as self-powered sensors, C-TENGs exhibit prolonged operational viability and responsiveness, adeptly discerning bending and motion induced by human interaction. The device's sensitivity, flexibility, and stability position it as a promising candidate for a diverse array of energy-harvesting applications and advanced healthcare endeavors. Specifically, envisaging sensitized wearable sensors for human activities underscores the multifaceted potential of C-TENGs in enhancing both energy-harvesting technologies and healthcare practices.

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Increasing interests have been directed toward the exploitation of origami techniques in developing biomimetic soft robots. There is a need for effective design solutions to exploit the properties of origami structure with simplified assembly and improved robotic mobility. In this study, inspired by human long-standing jumps, we present a soft electrostatically driven legged accordion fold actuator made by turning a flat paper into hollow polyhedron structure with a spring like rear and capable of electrostatic pad-assisted steering and carrying loads. Without the need for integration of external actuators, the actuator is composed of the electrostatic origami actuator itself supported by a single-fold leg with fast response, easy fabrication process, and low cost. Initiated by periodic deformation around the folding hinges caused by alternating current voltage and ground reaction forces, the actuators exhibit a unique jump-slide movement outperforming other existing soft electrostatic actuators/robots in terms of relative speed. We examined the effect of different geometric and external factors on the relative speed and highlighted the significance of body scale and short-edge panels as the elastic elements, as well as operating at resonance frequency in producing effective performances. Theoretical locomotion models and finite element analysis were carried out to interpret the working principle and validate experimental results.

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INTRODUCTION: GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC. METHODS: TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to screen out the downstream genes of GINS2. RESULTS: GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression. CONCLUSION: Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target.

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The movements of syringes and medications during an anesthetic case have yet to be systematically documented. We examine how syringes and medication move through the anesthesia work area during a case. We conducted a video-based observational study of 14 laparoscopic surgeries. We defined 'syringe events' as when syringe was picked up and moved. Medications were administered to the patient in only 48 (23.6%) of the 203 medication or syringe events. On average, 14.5 syringe movements occurred in each case. We estimate approximately 4.2 syringe movements for each medication administration. When a medication was administered to the patient (either through the IV pump or the patient port), it was picked up from one of 8 locations in the work area. Our study suggests that the syringe storage locations vary and include irregular locations (e.g., patient bed or provider's pockets). Our study contributes to understanding the complexity in the anesthesia work practices.

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ETHNOPHARMACOLOGICAL RELEVANCE: Polygonatum cyrtonema Hua (Huangjing) is a Chinese herb that is considered by ancient Chinese healers to have the effect of nourishing yin and moisturizing the lungs. It is clinically used to treat diseases of the pulmonary system, including non-small cell lung cancer. However, the precise active components and underlying mechanisms of Huangjing in the context of treating NSCLC remain uncertain. AIM OF THE STUDY: This study aimed to explore the active components and mechanisms of Huangjing for the treatment of NSCLC by means of data mining, network pharmacology, and in vitro and vivo experiments. MATERIALS AND METHODS: First, the main active compounds and key targets of Huangjing were predicted by network pharmacology. The potential key targets of Huangjing were molecularly docked with the main active compounds using Pymol. In vivo, we verified whether Huangjing and its main active compound have anti-lung cancer effects. Key targets were verified by PCR and immunohistochemistry. In vitro, we verified the effects of Huangjing's main active compound on the proliferation, apoptosis, and migration of A549 cells by CCK-8, colony formation, wound healing assay, and flow cytometry. Key targets and signaling pathway were validated by PCR and Western blot. RESULTS: The network pharmacology results suggested that ß-sitosterol was the main active substance. TP53, JUN, AKT1, MAPK14, ESR1, RELA, HIF1A, and RXRA were potential targets of Huangjing. Molecular docking results suggested that MAPK14, HIF-1α, and RXRA docked well with ß-sitosterol. In vivo tests also confirmed that Huangjing could significantly inhibit the growth of lung cancer tumors, while PCR and immunohistochemistry results suggested that the expression of HIF-1α was significantly decreased. Critically, KEGG analysis indicated that the PI3K/Akt/HIF-1α signaling pathway was recommended as one of the main pathways related to the anti-NSCLC effect of Huangjing. We conducted in vitro experiments to confirm the significant impact of ß-sitosterol on the proliferation, apoptosis, migration, and colony formation of A549 cells. Furthermore, our findings indicate that a high dosage of ß-sitosterol may effectively decrease the expression of HIF-1α, AKT1, JUN and RELA in A549 cells. Similarly, in vitro experiments also revealed that high doses of ß-sitosterol could inhibit the PI3K/Akt/HIF-1α signaling pathway. CONCLUSIONS: We discovered Huangjing and its main active ingredient, ß-sitosterol, can reduce HIF-1α, AKT1, JUN and RELA expression and decrease non-small cell lung cancer growth through the PI3K/Akt/HIF-1α signaling pathway.

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Metabolic reprogramming has been observed in cancer metastasis, whereas metabolic changes required for malignant cells during lymph node metastasis of esophageal squamous cell carcinoma (ESCC) are still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) of paired ESCC tumor tissues and lymph nodes to uncover the reprogramming of tumor microenvironment (TME) and metabolic pathways. By integrating analyses of scRNA-seq data with metabolomics of ESCC tumor tissues and plasma samples, we found nicotinate and nicotinamide metabolism pathway was dysregulated in ESCC patients with lymph node metastasis (LN+), exhibiting as significantly increased 1-methylnicotinamide (MNA) in both tumors and plasma. Further data indicated high expression of N-methyltransferase (NNMT), which converts active methyl groups from the universal methyl donor, S-adenosylmethionine (SAM), to stable MNA, contributed to the increased MNA in LN+ ESCC. NNMT promotes epithelial-mesenchymal transition (EMT) and metastasis of ESCC in vitro and in vivo by inhibiting E-cadherin expression. Mechanically, high NNMT expression consumed too much active methyl group and decreased H3K4me3 modification at E-cadherin promoter and inhibited m6A modification of E-cadherin mRNA, therefore inhibiting E-cadherin expression at both transcriptional and post-transcriptional level. Finally, a detection method of lymph node metastasis was build based on the dysregulated metabolites, which showed good performance among ESCC patients. For lymph node metastasis of ESCC, this work supports NNMT is a master regulator of the cross-talk between cellular metabolism and epigenetic modifications, which may be a therapeutic target.

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OBJECTIVES: Examining information presentation strategies that may facilitate patient education through patient portals is important for effective health education. METHODS: A randomized exploratory study evaluated information presentation (text or videos) and a chatbot in patient education and examined several performance and outcome variables (e.g., search duration, Decisional Conflict Scale, and eye-tracking measures), along with a simple descriptive qualitative content analysis of the transcript of chatbot. RESULTS: Of the 92 participants, those within the text conditions (n = 46, p < 0.001), had chatbot experiences (B =-74.85, p = 0.046), knew someone with IBD (B =-98.66, p = 0.039), and preferred to engage in medical decision-making (B =102.32, p = 0.006) were more efficient in information-searching. Participants with videos spent longer in information-searching (mean=666.5 (SD=171.6) VS 480.3 (SD=159.5) seconds, p < 0.001) but felt more informed (mean score=18.8 (SD=17.6) VS 27.4 (SD=18.9), p = 0.027). The participants' average eye fixation duration with videos was significantly higher (mean= 473.8 ms, SD=52.9, p < 0.001). CONCLUSIONS: Participants in video conditions were less efficient but more effective in information seeking. Exploring the trade-offs between efficiency and effectiveness for user interface designs is important to appropriately deliver education within patient portals. PRACTICE IMPLICATIONS: This study suggests that user interface designs and chatbots impact health information's efficiency and effectiveness.

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