The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC.

Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.

Borate bonds-containing pH-responsive chitosan hydrogel for postoperative tumor recurrence and wound infection prevention.

Chitosan has been widely used in biomedical fields due to its good antibacterial properties, excellent biocompatibility, and biodegradability. In this study, a pH-responsive and self-healing hydrogel was synthesized from 3-carboxyphenylboronic acid grafted with chitosan (CS-BA) and polyvinyl alcohol (PVA). The dynamic boronic ester bonds and intermolecular hydrogen bonds are responsible for the hydrogel formation. By changing the mass ratio of CS-BA and PVA, the tensile stress and compressive stress of hydrogel can controlled in the range of 0.61 kPa - 0.74 kPa and 295.28 kPa - 1108.1 kPa, respectively. After doping with tannic acid (TA)/iron nanocomplex (TAFe), the hydrogel successful killed tumor cells through the near infrared laser-induced photothermal conversion and the TAFe-triggered reactive oxygen species generation. Moreover, the photothermal conversion of the hydrogel and the antibacterial effect of CS and TA give the hydrogel a good antibacterial effect. The CS-BA/PVA/TAFe hydrogel exhibit good in vivo and in vitro anti-tumor recurrence and antibacterial ability, and therefore has the potential to be used as a powerful tool for the prevention of local tumor recurrence and bacterial infection after surgery.

The Relationship Between the Expression of CRBN in Peripheral Blood and the Severity and Prognosis of Adult Sepsis.

Objective: To investigate the correlation between the expression of cereblon (CRBN) protein in peripheral blood and the severity and prognosis of sepsis. Methods: A total of 130 patients with sepsis admitted to our hospital were selected as the observation subjects (sepsis group). The patients were divided into mild group, moderate group and severe group according to their conditions. The patients were divided into survival group and death group according to their living conditions within 28 days after admission. 130 health individuals were selected as the control group. The levels of CRBN mRNA, CRP and PCT in peripheral blood were detected. Results: The levels of serum CRBN mRNA, CRP, and PCT in patients with sepsis were higher than those in the control group (P<0.05); As the condition worsens, the levels of CRBN mRNA, CRP, and PCT gradually increase, and there are statistically significant differences among patients with mild, moderate, and severe sepsis; Correlation analysis showed that the expression of CRBN mRNA in sepsis patients was positively correlated with CRP, PCT levels, APACHE II score and SOFA score (P<0.05); the 28-day cumulative survival rate of patients with high CRBN mRNA expression was significantly lower than that of patients with low CRBN mRNA expression (P<0.05); compared with the survival group, the levels of serum CRBN mRNA, CRP and PCT in the death group were significantly higher (P<0.05); the AUC of death in sepsis patients diagnosed by CRBN mRNA, CRP and PCT was 0.961, the combined diagnostic efficacy was higher than that of single detection (P<0.05). Conclusion: The expression level of CRBN in the peripheral blood of patients with sepsis is increased, which is related to the severity and prognosis of the patients. The combination of CRP and PCT has certain diagnostic value for the death of sepsis patients.

Frailty-originated early rehabilitation reduces postoperative delirium in brain tumor patients: Results from a prospective randomized study.

Objective: To investigate the impact of frailty-originated, evidence-based early activity training on postoperative delirium in patients who have undergone brain tumor resection. Methods: A randomized controlled trial was conducted at the Second Affiliated Hospital of Zhejiang University School of Medicine, from July 2019 to June 2020. Data on the patients' general information, incidence and duration of delirium, duration of hospital stay, and activities of daily living were collected. From the first day after surgery, the patients were randomly assigned to either the traditional care group or the frailty-originated rehabilitation towards intracranial tumors using distinct evidence (FORTITUDE) group. Non-parametric, chi-square, and log-rank tests were used to compare the onset time and duration of postoperative delirium and activities of daily living performed by the participants between the two groups. Results: In total, 291 patients, 150 and 141 in the control group and FORTITUDE group, respectively, participated in the study. Patients in the FORTITUDE group had a lower incidence of postoperative delirium (15.6% vs. 28.7%, P â€‹= â€‹0.007), delayed onset of delirium (Z â€‹= â€‹-2.108, P â€‹= â€‹0.035), shorter duration of postoperative delirium (χ2 â€‹= â€‹26.67, P â€‹< â€‹0.001), shorter hospital stay (Z â€‹= â€‹-2.037, P â€‹= â€‹0.042), and higher scores in the activities of daily living one week (Z â€‹= â€‹-2.304, P â€‹= â€‹0.021) and one month (Z â€‹= â€‹-2.724, P â€‹= â€‹0.006) after surgery than in the control group. Conclusions: The FORTITUDE program was safe and effective in reducing the incidence and duration of postoperative delirium and improving the quality of life of patients who underwent brain tumor resection.

APOL1 Induces Pyroptosis of Fibroblasts Through NLRP3/Caspase-1/GSDMD Signaling Pathway in Ulcerative Colitis.

Background: Pyroptosis is a form of proinfammatory gasdermin-mediated programmed cell death. Abnormal infammation in the intestine is a critical risk factor for Ulcerative colitis (UC). However, at present, it is not clear whether pyroptosis of colonic fibroblasts is involved in the pathogenesis and progression of UC. Methods: In this study, key genes associated with UC were identified by bioinformatics analysis. Datasets were downloaded from the Gene Expression Omnibus (GEO) database (GSE193677). The differentially expressed genes were analyzed, and the hub genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed genes. We also downloaded the dataset from GEO for single-cell RNA sequencing (GSE231993). The expression of key genes was verified by immunohistochemistry, immunofluorescence and Western blot, and the specific pathways of key genes inducing pyroptosis in cell lines were explored. Results: The results of bioinformatics analysis showed that the expression of APOL1 and CXCL1 in UC tissues was significantly higher than that in normal tissues. The results of single-cell analysis showed that the two genes were co-localized to fibroblasts. These results were consistent with the results of immunohistochemistry and immunofluorescence colocalization in human intestinal mucosa specimens. Furthermore, APOL1 overexpression induced NLRP3-caspase1-GSDMD-mediated pyroptosis of fibroblasts, which was confirmed by Western blot. Conclusion: APOL1 induces pyroptosis of fibroblasts mediated by NLRP3-Caspase1-GSDMD signaling pathway and promote the release of chemokines CXCL1. Fibroblasts may play a crucial role in the pathogenesis and progression of UC.

Effectiveness and safety of oral anticoagulant therapy in patients with atrial fibrillation with prior gastrointestinal bleeding: A systematic review and meta-analysis.

Background: Gastrointestinal bleeding (GIB) commonly complicates anticoagulant therapy for patients with atrial fibrillation (AF). However, AF patients with prior GIB were excluded from most randomized controlled trials on anticoagulation therapy. Therefore, we conducted a systematic review and meta-analysis to assess the effect of oral anticoagulant (OAC) therapy in this specific population. Methods: Randomized trials and observational studies reporting the data about the resumption of OAC therapy among AF patients with prior GIB were included. The search was performed in the PubMed and Embase databasesup to March 2022. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method. Results: A total of 7 studies involving 57,623 patients were included. Compared with no anticoagulant therapy, OAC therapy was associated with decreased risks of stroke or systemic embolism (HR = 0.71, 95% CI: 0.59-0.84) and all-cause death (HR = 0.66, 95% CI: 0.60-0.72), but there was no significant difference in the risk of recurrent GIB (HR = 1.22, 95% CI: 0.94-1.59). Compared with vitamin K antagonists, non-vitamin K antagonist oral anticoagulants (NOACs) were associated with reduced risks of stroke or systemic embolism (HR = 0.61, 95% CI: 0.54-0.68), all-cause mortality (HR = 0.86, 95% CI: 0.75-0.99), major bleeding (HR = 0.75, 95% CI: 0.66-0.84), and GIB recurrence (HR = 0.83, 95% CI: 0.72-0.96). Conclusions: In AF patients with prior GIB, OAC therapy (especially NOACs) demonstrated superior effectiveness compared with no anticoagulant therapy.

Use of prescription medications associated with weight gain among US adults, 1999-2018: A nationally representative survey.

OBJECTIVE: This study aimed to evaluate trends in the use of obesogenic medications among adults. METHODS: Cross-sectional data on adults aged ≥20 years are from the 1999 to 2018 National Health and Nutrition Examination Survey (n = 52,340). Obesogenic medications were defined according to the 2015 Endocrine Society guidelines on the pharmacological management of obesity. Weight status was categorized according to BMI. Trends in prior 30-day use were evaluated. RESULTS: In NHANES 2017-2018, 20.3% of US adults used an obesogenic medication. Beta-blockers (9.8%) and antidiabetics (5.7%) were the most common; antipsychotics (1.0%) were the least common. Most common indications were disorders of glucose metabolism, hypertension, neuralgia or neuritis, heart disease, and musculoskeletal pain and/or inflammation. From 1999 to 2018, the proportional use of obesogenic medications increased for anticonvulsants (34.4% to 55.0%) but decreased for antidepressants (32.1% to 18.8%), antidiabetics (82.9% to 52.5%), and beta-blockers (83.9% to 80.7%). The proportional use of obesogenic medications was not associated with weight status, except for antipsychotics. CONCLUSIONS: Use of obesogenic medications was common. Differences in the proportional use of obesogenic medication may reflect changing availability of obesogenic versus nonobesogenic medications over time. The decision to prescribe a nonobesogenic alternative, if one exists, is guided by weighing the risks and benefits of available treatments.

Mean Body Weight, Height, Waist Circumference, and Body Mass Index Among Children and Adolescents: United States, 1999-2018.

Objective-This report presents trends in mean weight, recumbent length, height, waist circumference, and body mass index (BMI) among children and adolescents in the United States from 1999 through 2018.

Off-Label Underdosing or Overdosing of Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation: A Meta-Analysis.

Background: Several studies have investigated the role of off-label non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). We aimed to compare the effectiveness and safety outcomes between off-label underdose or overdose vs. on-label dose of NOACs in AF patients. Methods: The PubMed database was systematically searched until August 2021. Observational cohorts were included if they compared the outcomes of off-label underdose or overdose with on-label dose of NOACs in AF patients. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a fixed-effects model (I 2 ≤ 50%) or a random-effects model (I 2 > 50%). Results: A total of 15 observational studies were included. Compared with on-label dose of NOACs, off-label underdose of NOACs was associated with increased risks of stroke or systemic embolism (RR = 1.09, 95% CI 1.02-1.16), and all-cause death (RR = 1.29, 95% CI 1.10-1.52) but not ischemic stroke (RR = 1.34, 95% CI 0.76-2.36), myocardial infarction (RR = 1.08, 95% CI 0.92-1.28), major bleeding (RR = 0.97, 95% CI 0.89-1.05), intracranial hemorrhage (RR = 1.12, 95% CI 0.90-1.40), and gastrointestinal bleeding (RR = 0.96, 95% CI 0.85-1.07), whereas off-label overdose of NOACs was associated with increased risks of SSE (RR = 1.20, 95% CI 1.05-1.36), all-cause death (RR = 1.22, 95% CI 1.06-1.39), and major bleeding (RR = 1.33, 95% CI 1.16-1.52) but not gastrointestinal bleeding (RR = 1.18, 95% CI 0.99-1.42) and myocardial infarction (RR = 0.98, 95% CI 0.75-1.30). Conclusion: Compared with on-label dose of NOACs, off-label underdose was associated with increased risks of stroke or systemic embolism and all-cause death, whereas off-label overdose of NOACs was associated with increased risks of stroke or systemic embolism, all-cause death, and major bleeding.

Association of Direct Oral Anticoagulants vs. Vitamin K Antagonists With Fractures in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis.

Background: Current evidence regarding the application of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) on the fracture risk is inconsistent. Therefore, we conducted a meta-analysis to evaluate the fracture risk of DOACs vs. VKAs in patients with atrial fibrillation (AF). Methods: The PubMed and Embase databases were systematically searched until June 2021 for all the studies that reported oral anticoagulants in AF patients. The random-effect model with an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). Results: A total of 10 studies were included in this meta-analysis. Among AF patients receiving anticoagulants, DOAC users showed a reduced risk of any fracture compared to those with VKAs (RR = 0.80; 95% CI: 0.70-0.91) regardless of gender [males (RR = 0.79; 95% CI: 0.67-0.92) and females (RR = 0.71; 95% CI: 0.57-0.89)]. Apixaban (RR = 0.75; 95% CI: 0.60-0.92) and rivaroxaban (RR = 0.73; 95% CI: 0.61-0.88), but not dabigatran and edoxaban, were associated with a decreased risk of any fracture compared with VKAs. DOAC users had decreased risks of osteoporotic fractures (RR = 0.63; 95% CI: 0.47-0.84) and hip/pelvic fractures (RR = 0.88; 95% CI: 0.79-0.97) compared to those treated with VKAs. Conclusions: Our meta-analysis suggested that the use of DOACs was associated with a reduced risk of any fracture compared with VKAs. Further studies should confirm our findings.

Anthropometric Reference Data for Children and Adults: United States, 2015-2018.

Based on nationally representative anthropometric data, the National Center for Health Statistics (NCHS) has published reference tables on the distribution of various body measurements for the U.S. population (1-5). National Health and Nutrition Examination Survey (NHANES) data are the primary source of body measurement information for the U.S. population. These measurements reflect the mean weight, height, length, and various circumferences of U.S. children and adults. Anthropometry is a measure of nutritional or general health status, dietary adequacy, and growth. This report presents anthropometric reference data from the years 2015-2018 for U.S. children and adults.

Prevalence and Trends in HIV Infection and Testing Among Adults in the United States: The National Health and Nutrition Examination Surveys, 1999-2018.

BACKGROUND: HIV antibody testing has been included in the National Health and Nutrition Examination Survey, for ages 18-49 since 1999 and for ages 18-59 years since 2009 enabling estimation of trends in HIV prevalence as part of national surveillance in the U.S. household population. Self-reported HIV testing and antiretroviral use was also included in the survey since 1999. SETTING: A continuous household-based probability sample of the U.S. population. METHODS: From 1999 to 2018, 29,020 participants age 18-49 years were tested for HIV antibody and 34,092 participants age 18-59 years were asked about self-report of any previous HIV testing. RESULTS: HIV prevalence was 0.41% among those aged 18-59 in 2009-2018 with a nonsignificant trend over time among those aged 18-49 years from 1999-2002 to 2015-2018. However, significant declines in prevalence were seen among those aged 18-39 years (0.37%-0.11%), women (0.22%-0.06%) and non-Hispanic black persons (2.14%-0.80%). Participants aged 18-39 years self-reported a decline in HIV testing, whereas those aged 40-49 and 50-59 years, non-Hispanic black persons and women reported an increase in getting a HIV test. Prevalence of infection and self-reported history of HIV testing varied by demographic and risk groups. HIV testing among HIV-positive persons was 83.9%. Antiretroviral therapy among those HIV-positive was under 50%. CONCLUSION: Although total HIV prevalence and previous self-reported HIV testing remained stable for the last 20 years, there were significant declines in age and demographic subgroups. Prevalence for both outcomes varied by demographic and risk variables.

Developing equations to predict waist circumference measurements based on the National Heart, Lung, and Blood Institute method from the World Health Organization method.

PURPOSE: The purpose of the study was to convert waist circumference (WC) measurements obtained by the World Health Organization (WHO-WC) method to the National Heart, Lung, and Blood Institute (NHLBI-WC) method. METHODS: During 2016, the National Health and Nutrition Examination Survey participants aged 20 years and older had two different WC measurements taken (n = 2405). The mean differences in the WC between the NHLBI-WC and WHO-WC measurements were calculated. Multivariable prediction models were developed to predict the NHLBI-WC from the measured WHO-WC. Sensitivity and specificity of the abdominal obesity classification (AOC) were calculated for the measured WHO-WC and the predicted NHLBI-WC. Kappa coefficients were calculated to evaluate the agreements between the AOC derived from the NHLBI-WC and from the WHO-WC and the predicted NHLBI-WC. RESULTS: The mean differences between the NHLBI-WC and WHO-WC were 0.8 cm for males and 3.2 cm for females (P ≤ .05). Sensitivity of the AOC for the measured WHO-WC was 93% for males and 87% for females, and the specificity of the AOC was 97% or greater for both genders. Sensitivity and specificity of the AOC for the predicted NHLBI-WC were 95% or greater for both genders. The AOC derived from the predicted NHLBI-WC had higher agreements for both genders. CONCLUSIONS: The prediction equations provided may be used to predict the NHLBI-WC from the WHO-WC for comparability in WC estimates across studies.

Antidepressant Use Among Adults: United States, 2015-2018.

In 2018, an estimated 7.2% of American adults had a major depressive episode in the past year (1). Depression is associated with diminished quality of life and increased disability (2). Antidepressants are one of the primary treatments for depression (3) and are among the most frequently used therapeutic medications in the United States (4). This data brief provides recent prevalent estimates for antidepressant use among U.S. adults aged 18 and over, by age, sex, race and Hispanic origin, and education. Trends in antidepressant use over the decade from 2009-2010 through 2017-2018 are described.

Prevalence of Prescription Pain Medication Use Among Adults: United States, 2015-2018.

Prescription pain medications are used to treat pain due to injury, surgery, and health conditions, such as arthritis and cancer. While opioids may be prescribed together with nonopioid pain medications, nonpharmacologic and nonopioid-containing pharmacologic therapies are preferred for management of chronic pain, where appropriate (1). This report shows the percentage of U.S. adults who, in the past 30 days, used one or more prescription pain medications, used prescription opioid medications, or used nonopioid prescription pain medications (without prescription opioids) in 2015-2018.

MicroRNA-19b-3p suppresses gastric cancer development by negatively regulating neuropilin-1.

BACKGROUND: Gastric cancer (GC) remains one of the most common digestive malignancies worldwide and ranked third causes of cancer-related death. Mounting evidence has revealed that miRNAs exert critical regulatory roles in GC development. METHODS: Immunohistochemistry (IHC) and western blot assay were performed to determine the protein expression levels of neuropilin-1 (NRP1) and mRNA levels were confirmed by quantitative RT-PCR (qRT-PCR) in GC tissues. Kaplan-Meier analysis was performed to evaluate the prognostic value of NRP1 in GC. Knockdown of NRP1 was conducted to analyse its function in vitro and vivo. Luciferase reporter assay, western blot and qRT-qPCR were employed to identify the miRNAs which directly targeted NRP1. Furthermore, Bioinformatics analysis and experimental verification were used to explore the potential molecular mechanism and signalling pathway. RESULTS: In the current study, we revealed that NRP1 was highly expressed in GC tumor tissues and was associated with poor prognosis in GC patients. NRP1 knockdown inhibited GC cell growth, migration and invasion in vitro, while suppressed GC xenograft tumor development in vivo. Bioinformatics analysis predicted that miR-19b-3p down-regulated NRP1 expression by targeting its 3'-UTR. Functional assay demonstrated that miR-19b-3p inhibited GC cell growth, migration and invasion via negatively regulating NRP1. Overexpression NRP1 partially reversed the regulatory effect of miR-19b-3p. Moreover, we showed that miR-19b-3p/NRP1 axis regulated the epithelial-to-mesenchymal transition and focal adhesion in GC, which might contribute the GC development and progression. CONCLUSIONS: Taken together, our findings suggest a regulatory network of miR-19b-3p/NRP1 in GC development. The miR-19b-3p/NRP1 axis might be further explored as a potential diagnostic and therapeutic target in GC.

Prescription Drug Use in the United States, 2015-2016.

Monitoring prescription drug use patterns at the population level (1) can inform research and clinical practice. These patterns may shift over time in response to changing health needs, updated clinical guidelines (2), policy changes, and other factors (1,3). The percentage of the U.S. population that used one or more prescription drugs increased from 1999-2000 through 2007-2008 (4). This report describes prescription drug use by age, sex, and race and Hispanic origin in 2015-2016 and trends over the preceding decade.

Factors Associated with Prescription Opioid Analgesic Use in the US Population, 2011-2014.

OBJECTIVE: This study examined factors associated with prescription opioid analgesic use in the US population using data from a nationally representative sample. It focused on factors previously shown to be associated with opioid use disorder or overdose. Variations in the use of different strength opioid analgesics by demographic subgroup were also examined. METHODS: Data came from respondents aged 16 years and older who participated in the National Health and Nutrition Examination Survey (2011-2014). Respondents were classified as opioid users if they reported using one or more prescription opioid analgesics in the past 30 days. RESULTS: Opioid users reported poorer self-perceived health than those not currently using opioids. Compared with those not using opioids, opioid users were more likely to rate their health as being "fair" or "poor" (40.4% [95% confidence interval {CI} = 34.9%-46.2%] compared with 15.6% [95% CI = 14.3%-17.1%]), experienced more days of pain during the past 30 days (mean = 14.3 [95% CI = 12.9-15.8] days compared with 2.3 [95% CI = 2.0-2.7] days), and had depression (22.5% [95% CI = 17.3%-28.7%] compared with 7.1% [95% CI = 6.2%-8.0%]). Among those who reported using opioids during the past 30 days, 18.8% (95% CI = 14.4%-24.1%) reported using benzodiazepine medication during the same period and 5.2% (95% CI = 3.5%-7.7%) reported using an illicit drug during the past six months. When opioid strength was examined, a smaller percentage of adults aged 60 years and older used stronger-than-morphine opioids compared with adults aged 20-39 and 40-59 years. CONCLUSIONS: Higher percentages of current opioid users than nonusers reported having many of the factors associated with opioid use disorder and overdose.

Prevalence of Total, Diagnosed, and Undiagnosed Diabetes Among Adults: United States, 2013-2016.

Diabetes is a major cause of morbidity and mortality in the United States (1-3). Diabetes can be present but undiagnosed, meaning that a person can have diabetes but not report having ever been told by a doctor or health professional that they have the condition. Type 2 diabetes can progress over an extended time period with gradual, often unnoticed, changes occurring before diagnosis. If left unmanaged, diabetes may contribute to serious health outcomes including neuropathy, nephropathy, retinopathy, coronary artery disease, stroke, and peripheral vascular disease (4). This report presents the prevalence of total, diagnosed, and undiagnosed diabetes in U.S. adults in 2013-2016.