General Defluoroalkylation of Trifluoromethylarenes with Both Electron-Donating and -Withdrawing Alkenes.

The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.

A study on the effect of clinical intervention of evidence-based nursing measures on complications in patients after breast-conserving surgery.

BACKGROUND: Breast-conserving surgery is an important treatment for breast cancer, which not only eradicates the disease, but also protects the integrity of the breast, however, postoperative nausea and vomiting often bother patients. OBJECTIVE: This study examines the effects of evidence-based nursing practices on nausea and vomiting in patients after breast-conserving surgery, with the aim of providing new perspectives for clinical nursing practice. METHODS: One hundred and sixty patients who underwent breast-conserving surgery from January 2023 to December 2023 in Fudan University Shanghai Cancer Center were enrolled. The patients were divided into an intervention group (evidence-based nursing group) and a control group (conventional nursing group) using the random number table method, both groups comprised 80 patients. The control group used conventional nursing methods, and the intervention group added evidence-based nursing intervention on this basis. Comparative analysis focused on the incidence of nausea and vomiting, quality of life metrics, and postoperative satisfaction. RESULTS: In the intervention group, notably lower incidence rates of postoperative nausea and vomiting were observed compared to the control group within both the 0-24 hour and 24-48-hour postoperative periods (P< 0.05). Furthermore, the intervention group exhibited significantly higher scores across all five dimensions as well as the overall score of the FACT-B scale in comparison to the control group (P< 0.05), accompanied by heightened satisfaction with the nursing staff. CONCLUSION: This study demonstrated the positive clinical intervention effects of evidence-based nursing measures and emphasized their importance in improving postoperative nausea and vomiting and quality of life. Future studies are expected to incorporate evidence-based nursing practices into nursing care to improve patient recovery and overall quality of care.

[Efficiency of different large language models in China in response to consultations about PCa-related perioperative nursing and health education].

OBJECTIVE: To evaluate the efficiency of the four domestic language models, ERNIE Bot, ChatGLM2, Spark Desk and Qwen-14B-Chat, all with a massive user base and significant social attention, in response to consultations about PCa-related perioperative nursing and health education. METHODS: We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases, and inputted the questions into each of the four language models for simulation consultation. Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy, comprehensiveness, understandability, humanistic care, and case analysis. We evaluated and compared the performance of the four models using visualization tools and statistical analyses. RESULTS: All the models generated high-quality texts with no misleading information and exhibited satisfactory performance. Qwen-14B-Chat scored the highest in all aspects and showed relatively stable outputs in multiple tests compared with ChatGLM2. Spark Desk performed well in terms of understandability but lacked comprehensiveness and humanistic care. Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis. The overall performance of ERNIE Bot was slightly inferior. All things considered, Qwen-14B-Chat was superior to the other three models in consultations about PCa-related perioperative nursing and health education. CONCLUSION: In PCa-related perioperative nursing, large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support, so as to improve the patient compliance and the quality of clinical treatment and nursing.

Synovial microenvironment in temporomandibular joint osteoarthritis: crosstalk with chondrocytes and potential therapeutic targets.

Temporomandibular joint osteoarthritis (TMJOA) is considered to be a low-grade inflammatory disease involving multiple joint tissues. The crosstalk between synovium and cartilage plays an important role in TMJOA. Synovial cells are a group of heterogeneous cells and synovial microenvironment is mainly composed of synovial fibroblasts (SF) and synovial macrophages. In TMJOA, SF and synovial macrophages release a large number of inflammatory cytokines and extracellular vesicles and promote cartilage destruction. Cartilage wear particles stimulate SF proliferation and macrophages activation and exacerbate synovitis. In TMJOA, chondrocytes and synovial cells exhibit increased glycolytic activity and lactate secretion, leading to impaired chondrocyte matrix synthesis. Additionally, the synovium contains mesenchymal stem cells, which are the seed cells for cartilage repair in TMJOA. Co-culture of chondrocytes and synovial mesenchymal stem cells enhances the chondrogenic differentiation of stem cells. This review discusses the pathological changes of synovium in TMJOA, the means of crosstalk between synovium and cartilage, and their influence on each other. Based on the crosstalk between synovium and cartilage in TMJOA, we illustrate the treatment strategies for improving synovial microenvironment, including reducing cell adhesion, utilizing extracellular vesicles to deliver biomolecules, regulating cellular metabolism and targeting inflammatory cytokines.

Cluster Randomized Trial of Diabetes Group Visits in Community Health Centers across the Midwest.

BACKGROUND: Diabetes group visits (GVs) have not been rigorously evaluated in community health centers. METHODS: This cluster randomized controlled study recruited adults with diabetes mellitus with glycosylated hemoglobin, A1C greater than or equal to eight percent: 75 intervention and 120 usual care. Group visit patients completed a six-month program. Primary outcome was A1C change from baseline to 12 months. RESULTS: Participants improved their A1C by 0.38%-0.40% with no difference across arms (p=.63). Group visit patients improved their diabetes social support, knowledge, and distress and were more likely to receive guideline-based care compared with control. Group visit patients with anxiety or depression were more likely to have a visit with behavioral health compared with usual care (p=.02). CONCLUSIONS: Community health center patients with diabetes had improvements in glucose control across arms. Group visits improved the receipt of mental health care and guideline-based care.

The novel up/down-conversion dual-emission carbon dots for dual-channel ratiometric fluorescence detection of pH and Cu2.

Up/down-conversion dual-emission carbon dots (U/D-CDs) are rare and have potential in analytical sensing. Herein, a kind of novel U/D-CDs was prepared successfully by a one-step solvothermal method. The prepared U/D-CDs exhibited similar dual-emission behaviors at excitation wavelengths of 300 nm and 680 nm, respectively. In addition, U/D-CDs displayed good photostability and salt-resistance. Due to the protonation-deprotonation, U/D-CDs showed strong pH dependence in the pH range of 2.0-8.0, which developed an up/down-conversion dual-channel ratiometric fluorescence (FL) probe of pH. The FL intensity of U/D-CDs can be effectively quenched by Cu2+ through the static quenching effect. Meanwhile, an obvious color change from yellow-green to blue can be observed under ultraviolet light with the increase of Cu2+ concentration. The up/down-conversion dual-channel ratiometric fluorescence sensor can be used for the visual sensing of pH and Cu2+, which also eliminates background signals and improves its accuracy and selectivity in complex samples.

A nurse driven care management program to engage older diabetes patients in personalized goal setting and disease management.

Background and Aims: Multiple diabetes care guidelines have called for the personalization of risk factor goals, medication management, and self-care plans among older patients. Study of the implementation of these recommendations is needed. This study aimed to test whether a patient survey embedded in the Electronic Healthcare Record (EHR), coupled with telephonic nurse care management, could engage patients in personalized goal setting and chronic disease management. Methods: We conducted a single-center equal-randomization delayed comparator trial at the primary care clinics of the University of Chicago Medicine from 2018.6 to 2019.12. Patients over the age of 65 years with type 2 diabetes with an active patient portal account were recruited and randomized to receive an EHR embedded goal setting and preference survey immediately in the intervention arm or after 6 months in the delayed intervention control arm. In the intervention arm, nurses reviewed American Diabetes Association recommendations for A1C goals based on health status class, established personalized goals, and provided monthly telephonic care management phone calls for a maximum of 6 months. Our primary outcome was the documentation of a personalized A1C goal in the EHR. Results: A total of 100 patients completed the trial (mean age, 72.51 [SD, 5.22] years; mean baseline A1C, 7.14% [SD, 1.06%]; 68% women). The majority were in the Healthy (59%) followed by Complex (30%) and Very Complex (11%) health status classes. Documentation of an A1C goal in the EHR increased from 42% to 90% (p < 0.001) at 6 months in the intervention group and from 54% to 56% in the control group. Across health status classes, patients set similar A1C goals. Conclusions: Older patients can be engaged in personalized goal setting and disease management through an embedded EHR intervention. The clinical impact of the intervention may differ if deployed among older patients with more complex health needs and higher glucose levels. Trial Registration: ClinicalTrials.gov Identifier: NCT03692208.

Coconstruction of Supramolecular Lithium-Conducting Cross-Linked Networks Based on PVDF and Triblock Polymer Nanomicrosphere Solid-State Polymer Electrolytes for Lithium-Metal Batteries.

Uneven lithium plating and low ionic conductivity currently impede the realization of high-capacity rechargeable lithium metal batteries. And the conventional poly(ethylene oxide) (PEO) solid-state electrolytes are unsuitable for high-energy-density Li anode applications due to their low lithium-ion transference number and high reactivity with Li metal, leading to detrimental dendrite formation and potentially hazardous exothermic reactions with the electrolyte. In this study, we employ a supramolecular approach to develop a novel polymer solid-state electrolyte based on poly(vinylidene fluoride) (PVDF) and a novel triblock polymer nanomicrosphere, (poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone), (PCL-PEG-PCL). The abundance of carbonyl and ether-oxygen functional groups in PCL-PEG-PCL enhances the lithium coordination environment within the polymer solid-state electrolyte. Additionally, the original C-F moieties of PVDF form hydrogen bonds with C-H and terminal hydroxyl groups in PCL-PEG-PCL, collectively creating a multichannel fast Li+-conducting supramolecular cross-linked network. The resulting electrolyte demonstrates a high ionic conductivity of 1.4 × 10-3 S cm-1 and an extended electrochemical window of 5.2 V. Moreover, the electrolyte exhibits a high lithium-ion transference number (tLi+ = 0.63) at room temperature and exhibits excellent interfacial compatibility with the lithium metal anode. For the resulting electrolyte utilized in LiFePO4 batteries, the capacity retention of the cells assembled with this electrolyte exceeds 91.3% after 1000 cycles at 25 °C and 2 C (0.281 mA cm-2).

The role of YAP/TAZ on joint and arthritis.

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common forms of arthritis with undefined etiology and pathogenesis. Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ), which act as sensors for cellular mechanical and inflammatory cues, have been identified as crucial players in the regulation of joint homeostasis. Current studies also reveal a significant association between YAP/TAZ and the pathogenesis of OA and RA. The objective of this review is to elucidate the impact of YAP/TAZ on different joint tissues and to provide inspiration for further studying the potential therapeutic implications of YAP/TAZ on arthritis. Databases, such as PubMed, Cochran Library, and Embase, were searched for all available studies during the past two decades, with keywords "YAP," "TAZ," "OA," and "RA."

Evaluating Quality of Care for Patients with Asthma in the Readmission Penalty Era.

Rationale: Asthma poses a significant burden for U.S. patients and health systems, yet inpatient care quality is understudied. National chronic obstructive lung disease (COPD) readmission policies may affect inpatient asthma care through hospital responses to these policies because of imprecise diagnosis and identification of patients with COPD and asthma. Objectives: Evaluate inpatient care quality for patients hospitalized with asthma and potential collateral effects of the Medicare COPD Hospital Readmissions Reduction Program (HRRP). Methods: This was a retrospective cohort study of patients aged 18-54 years hospitalized for asthma across 924 U.S. hospitals (Premier Healthcare Database). Results: Care quality for patients with asthma was evaluated before HRRP implementation (n = 20,820; January 2010-September 2014) and after HRRP implementation (n = 26,885; October 2014-December 2018) using adherence to inpatient care guidelines (recommended, nonrecommended, and "ideal care" [all recommended with no nonrecommended care]). Between 2010 and 2018, at least 80% of patients received recommended care annually. Recommended care decreased similarly (rate of 0.02%/mo) after versus before HRRP (P = 0.8). Nonrecommended care decreased more rapidly after HRRP (rate of 0.29%/mo) versus before HRRP (rate of 0.17%/mo; P < 0.001), with changes driven largely by decreased antibiotic prescribing. Ideal care increased more rapidly after HRRP (rate of 0.25%/mo) versus before HRRP (rate of 0.17%/mo; P = 0.02), with changes driven largely by nonrecommended care improvements. Conclusions: Post-HRRP trends suggest asthma care improved with increased rates of guideline concordance in nonrecommended and ideal care. Although federal policies (e.g., HRRP) may have had positive collateral effects, such as with asthma care, parallel care efforts, including antibiotic stewardship, likely contributed to these improvements.

Neighborhood-level factors associated with COVID-19 vaccination rates: a case study in Chicago.

INTRODUCTION: Chicago's deeply-rooted racial and socioeconomic residential segregation is a pattern mirrored in other major cities, making it a prototype for studying the uptake of public health interventions across the US. Residential segregation is related to availability of primary care, sense of community, and trust in the healthcare system, components which are essential in the response to crises like Covid-19 in which vaccine rollout was primarily community-based. We aimed to evaluate the association between rates of access to primary care and community-belonging with Covid-19 vaccination within Chicago's neighborhoods. METHODS: Data from Chicago Department of Public Health (12/2020-6/2022) on Covid-19 vaccination rates, race/ethnicity (% Black and % Hispanic/Latinx residents), age (% >65), gender (% female), socioeconomic status (% below the federal poverty line), access to needed care rate, and rate of self-reported sense of community-belonging on the neighborhood level were analyzed. Linear mixed models (LMMs) were used to study the impact of variables on vaccination; each neighborhood was added as a random effect to account for with-community association. RESULTS: The average Covid-19 vaccination rates across Chicago's neighborhoods was 79%, ranging from 37 to 100%, with median 81%. We found that Covid-19 vaccination rates were positively correlated with access to needed care (p < 0.001) and community-belonging (p < 0.001). Community areas that had lower vaccination rates had greater percentage of Black residents (p < 0.0001) and greater poverty rates (p < 0.0001). After adjusting for poverty, race, gender and age in the models, the association between vaccination rates and access to care or community-belonging were no longer significant, but % Black residents and poverty remained significant. CONCLUSIONS: Though access to needed primary care and community-belonging are correlated with vaccination rates, this association was not significant when controlling for demographic factors. The association between poverty, race and vaccination status remained significant, indicating that socioeconomic and racial disparities across Chicago drive Covid-19 vaccine recommendation adherence regardless of care access. Understanding how poverty, and its intersectional relation to race and primary care access, affects vaccination should be a priority for public health efforts broadly.

BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion.

B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.

Assembly of porous filaments by interfacial complexation of nanochitin-based Pickering emulsion and seaweed alginate.

Interfacial polyelectrolyte complexation spinning is an all-water, easy-to-operate method for production of composite filaments. Herein, this concept is extended to interfacial polyelectrolyte-emulsion complexation (IPEC) that better encodes structural and functional attributes of biomass substances into the filaments. This allows for formation of composite filaments by drawing contacting oppositely-charged chitin nanofiber-stabilized Pickering emulsion and seaweed alginate solution. The parameters affecting spinnability of the system including water-to-oil ratio, alginate concentration, and pH are comprehensively elucidated to support the design and application of IPEC. The composite filaments exhibit varied diameters and diverse porous structures that are adjustable by properties of Pickering droplets. The droplet diameter of precursor emulsion and pore size in the filaments are well correlated, revealing controllability of the IPEC spinning. The filaments are mechanically robust in dry condition and show stable performance even in wet condition. The release rate of filaments that is pre-loaded with hydrophilic drug is regulated by the internal pore size, showing capability on sustained release. This study offers a new perspective toward dry spinning via interfacial complexation of complicated nanochitin-based structural building blocks, aiming at developing high-performance fiber materials for advanced applications.

Diabetes Life Expectancy Prediction Model Inputs and Results From Patient Surveys Compared With Electronic Health Record Abstraction: Survey Study.

Background: Prediction models are being increasingly used in clinical practice, with some requiring patient-reported outcomes (PROs). The optimal approach to collecting the needed inputs is unknown. Objective: Our objective was to compare mortality prediction model inputs and scores based on electronic health record (EHR) abstraction versus patient survey. Methods: Older patients aged ≥65 years with type 2 diabetes at an urban primary care practice in Chicago were recruited to participate in a care management trial. All participants completed a survey via an electronic portal that included items on the presence of comorbid conditions and functional status, which are needed to complete a mortality prediction model. We compared the individual data inputs and the overall model performance based on the data gathered from the survey compared to the chart review. Results: For individual data inputs, we found the largest differences in questions regarding functional status such as pushing/pulling, where 41.4% (31/75) of participants reported difficulties that were not captured in the chart with smaller differences for comorbid conditions. For the overall mortality score, we saw nonsignificant differences (P=.82) when comparing survey and chart-abstracted data. When allocating participants to life expectancy subgroups (<5 years, 5-10 years, >10 years), differences in survey and chart review data resulted in 20% having different subgroup assignments and, therefore, discordant glucose control recommendations. Conclusions: In this small exploratory study, we found that, despite differences in data inputs regarding functional status, the overall performance of a mortality prediction model was similar when using survey and chart-abstracted data. Larger studies comparing patient survey and chart data are needed to assess whether these findings are reproduceable and clinically important.

Enhancing Chronic-Disease Education through Integrated Medical and Social Care: Exploring the Beneficial Role of a Community Teaching Kitchen in Oregon.

Teaching kitchens (TKs) are rapidly being utilized as models to integrate culinary education and chronic-disease education into healthcare settings. Our observational study details the structure and organizational processes (e.g., referral, services, medical and social care integration) of the Community TK at Providence Milwaukie Hospital in Portland, OR. We utilize electronic medical-record data from engaged TK participants (n = 3077) to evaluate between the association of engagement and clinical outcomes (e.g., HbA1c, blood pressure, weight and cholesterol). Mean baseline HbA1c of Highly Engaged TK patients with diabetes (n = 88) reduced from 9.8% to 8.6% at 6 months (p < 0.0001) and sustained significant reductions at 12, 18, 24, 30, and 36 months (p < 0.05). Highly Engaged patients with hypertension (n = 152) had significant, sustained reductions in blood pressure (p < 0.0001). Engaged patients in the same high-risk groups also had significant improvements in HbA1c and blood pressure. Both engagement subgroups had moderate improvements in weight change and cholesterol. This study shows promising associations of TK services that promote chronic-disease self-management with improved clinical outcomes among higher risk patients (e.g., high blood pressure, high HbA1c, high low-density lipoprotein) with different medical issues (e.g., diabetes, obesity) and social barriers (e.g., food insecurity).

Evaluating Effects of Virtual Diabetes Group Visits in Community Health Centers During the COVID-19 Pandemic.

Diabetes is the seventh leading cause of death in the US. Diabetes group visits (GVs), which include group education and individual medical visits have been shown to improve clinical outcomes. However, few studies have evaluated virtual GVs. We conducted a single-arm pilot study to test the impact of virtual diabetes GVs in Midwestern community health centers (CHCs). Adult patients with diabetes participated in monthly virtual GVs for 6 months. Surveys and chart abstraction were used to assess patient-reported and clinical outcomes. Five CHCs implemented virtual GVs with 34 patients attending at least one session. Virtual GVs show promise as evidenced by these findings: (1) Patients had a nonsignificant decrease in A1C. (2) In the subgroup of patients with baseline A1C ≥ 9%, there was a significant decrease in A1C. (3) Patients had significant increases in diabetes knowledge and support as well as a decrease in diabetes distress. Future studies with a larger sample size and a control comparison group are needed to assess the impact of virtual GVs on patient outcomes.

Optimized CRISPR/Cas9 system for gene knockout in chicken DF1 cells.

The editing efficiency primarily hinders the utility of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology in poultry. For a better understanding of the factors that influence the efficiency of gene knockout mediated by CRISPR/Cas9 in chicken DF1 cells, the single or dual single guide RNA (sgRNA) targeted exon regions of genes (taking anti-Müllerian hormone, TGF-beta receptor type-2 and Peroxisome proliferator-activated receptor gamma as examples) were designed. The sgRNA-CRISPR/Cas9 vectors with corresponding reporter vectors were transfected into DF1 cells. T7 endonuclease 1 (T7E1) and amplicon sequencing assay were compared for evaluating genome editing efficiency and the indel profiles were analyzed based on the data of amplicon sequencing. Meanwhile, to evaluate the precision of Cas9 cleavage, we also analyzed the homology of small insertion with the nucleotides of upstream and downstream of cleave sties. The surrogate reporter systems showed strong enrichment function, and the indel percentages were increased after puromycin selection. The indel ratios of T7E1 assay were lower than amplicon sequencing assay, which indicated T7E1 isn't fit to be used as the sole evaluation criterion for the targeting efficiency of CRISPR/Cas9. Based on the amplicon sequencing analysis, the editing efficiency showed noticeable differences among cells treated with different sgRNAs. However, the variety of indel efficiencies was not related to the GC content of sgRNA or chromosome types of targeted genes. The results showed that the dual sgRNA might not raise the indel ratios compared with individual sgRNA, but they could increase the ratios of the fragment deletions. The present study suggested that the surrogate reporter was an effective method to promote the editing efficiencies of CRISPR/Cas9 in chicken cells. The dual sgRNA could increase the fragment deletions, and the sensitivity of amplicon sequencing to detect cleavage was higher than the T7 endonuclease 1 assay. These results are essential to improve the application of CRISPR/Cas9 technology in chicken cells.

Population Health Management Approach to Depression Symptom Monitoring in Primary Care via Patient Portal: A Randomized Controlled Trial.

Depression is undertreated in primary care. Using patient portals to administer regular symptom assessments could facilitate more timely care. At an urban academic medical center outpatient clinic, patients with active portal accounts and depression on their problem list or a positive screen in the past year were randomized to assessment during triage at visits (usual care) versus usual care plus assessment via portal (population health care). Portal invitations were sent regardless of whether patients had scheduled appointments. More patients completed assessments in the population health care arm than usual care: 59% versus 18%, P < 0.001. Depression symptoms were more common among patients who completed their initial assessment via the portal versus in the clinic. In the population health care arm, 57% (N = 80/140) of patients with moderate-to-severe symptoms completed at least 1 follow-up assessment versus 37% (N = 13/35) in usual care. A portal-based population health approach could improve depression monitoring in primary care.

Role of m6A modification in immune microenvironment of digestive system tumors.

Digestive system tumors are huge health problem worldwide, largely attributable to poor dietary choices. The role of RNA modifications in cancer development is an emerging field of research. RNA modifications are associated with the growth and development of various immune cells, which, in turn, regulate the immune response. The majority of RNA modifications are methylation modifications, and the most common type is the N6-methyladenosine (m6A) modification. Here, we reviewed the molecular mechanism of m6A in the immune cells and the role of m6A in the digestive system tumors. However, further studies are required to better understand the role of RNA methylation in human cancers for designing diagnostic and treatment strategies and predicting the prognosis of patients.

Structural Maintenance of Chromosome Protein 4 Promotes the Progression of Cardia Adenocarcinoma via Regulation of the Wnt/ß-catenin Signaling Pathway.

BACKGROUND: Structural maintenance of chromosome protein 4 (SMC4) is crucial for chromosome assembly and separation, but its role and mechanism in cardia adenocarcinoma (CA) are unknown. METHODS: SMC4 expression levels were initially detected by protein profiling in 20 pairs of CA tumor tissues and adjacent normal tissues. The level of SMC4 expression in CA cells was then evaluated using a western blot analysis. Cell proliferation was evaluated by CCK-8 and clone formation tests. Scratch and transwell tests were used to investigate cell migration as well as invasion, while through the flow cytometry, we examined the cell apoptosis and progression of the cell cycle. The regulatory effects of the epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin pathway were investigated using western blot. A tumorigenesis experiment was used to investigate the influence of SMC4 on tumor development in nude mice. RESULTS: This study showed overexpression of SMC4 in CA tissues and cells. Knockdown of SMC4 can significantly inhibit the proliferation, migration and invasion, stimulate cell apoptosis, induce cell cycle arrest in the G0/G1 phase of CA cells, and inhibit tumor growth in vivo. In addition, down-regulation of SMC4 resulted in decreased expression of Bcl-2, Cyclin D1, CDK4, CDK6, ß-catenin, phosphorylated GSK-3ß, N-cadherin, and Vimentin, with an increased level of proteins, i.e., Bax, cleaved-caspase3, and E-cadherin. When SMC4 was overexpressed, these effects were reversed. CONCLUSION: SMC4 can facilitate the biological progression of CA, suggesting that SMC4 could be a potential therapeutic target for the disease.