Prevalence and impact of metabolic associated fatty liver disease in non-metastatic breast cancer women at initial diagnosis: a cross-sectional study in China.

PURPOSE: The epidemiologic data of metabolic associated fatty liver disease (MAFLD) in breast cancer (BC) patients remains limited. We aimed to investigate the prevalence and clinicopathological characteristics of hepatic steatosis (HS) and MAFLD in Chinese BC women at initial diagnosis. METHODS: 3217 non-metastatic primary BC women with MAFLD evaluation indexes at initial diagnosis and 32,170 age-matched (in a 1:10 ratio) contemporaneous health check-up women were enrolled. RESULTS: The prevalence of HS (21.5% vs. 19.7%, p = 0.013) and MAFLD (20.8% vs. 18.6%, p = 0.002) were significantly higher in BC women than in health check-ups, respectively. Meanwhile, the prevalence of HS/MAFLD among elderly BC women (≥ 60 years) was significantly higher than the health check-ups (38.7%/37.6% vs 31.9%/30.8%), respectively. In BC women with HS/MAFLD, the prevalence of overweight/obesity was up to 85.7%/88.6%, dyslipidemia and elevated blood pressure were 63.2%/63.7% and 59.7%/61.7%, respectively. No statistical significance of the expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER-2) and Ki67 were found between BC women with HS/MAFLD and BC women without HS/MAFLD. After adjustment, BC women with HS showed significantly higher risk of lymph node metastasis than BC women without HS. Subjects with HS/MAFLD had higher risks of overweight/obesity, dyslipidemia, elevated blood pressure, hyperuricemia, and elevated enzymes than those without HS/MAFLD. CONCLUSIONS: Compared with health check-ups, BC patients have higher prevalence of HS/MAFLD. HS/MAFLD coexist with high prevalence of metabolic complications, and the risk of lymph node metastasis was significantly higher in BC women with HS than in BC women without HS.

Cross-sectional study of hepatitis B virus infection in female breast cancer patients in China for the first time diagnosed.

BACKGROUND: The correlation between breast cancer and hepatitis B virus (HBV) remains inconclusive. This study aims to explore the serological status of HBV infection and past infection in different age groups of female breast cancer patients, patients with benign breast diseases, and individuals undergoing routine physical examinations. METHODS: Serum data on HBV serological markers were collected and analyzed from 6072 female breast cancer patients first diagnosed from September 2012 to July 2020 at the First Affiliated Hospital of Chongqing Medical University, along with 4019 women with benign breast diseases and 54,740 healthy females undergoing routine physical examinations in the same period. The data were stratified by age for comparison between groups. RESULTS: The prevalence of HBV infection and past infection in the breast cancer group (7.9%, 55.1%) was higher than that in the benign breast disease group (6.5%, 39.1%) and the healthy females group(5.0%, 17.6%);the rate of only HBV surface antibody positivity (HBsAb ( +)) in the breast cancer group (10.3%) was lower than that in the benign breast disease group (26.9%) and the healthy females group (49.2%), with significant differences between the three groups (p < 0.05). Stratified by age, the prevalence of HBV infection in the breast cancer group (8%, 8.9%) and benign breast disease group (7.75%, 8.1%)was higher than that in the healthy females group (4.5%, 6.3%) in the 30-39 and 40-49 age group, respectively. The past infection rate of HBV in the breast cancer group (24.8%, 45.0%) was higher than that in the benign breast disease group (16.1%, 35.4%) in the ≤ 29 and 30-39 age group, respectively.. The past infection rate of HBV in the breast cancer group was higher than that in the healthy females group in all age groups, while the rate of only HBsAb ( +) in the breast cancer group was lower than that in the benign breast disease group and the routine physical examination group in all age groups. CONCLUSIONS: Breast cancer women and women with benign breast diseases have higher rates of hepatitis B virus infection and previous infections, with more significant differences among middle-aged women. Breast cancer women and women with benign breast diseases have lower rates of only HBsAb ( +) for HBV.

Prevalence and risk factors of thyroid nodules in breast cancer women with different clinicopathological characteristics: a cross-sectional study.

BACKGROUND: Association between breast cancer (BC) and thyroid nodules (TNs) is still unclear. This research was to estimate the prevalence and risk factors of TN in Chinese BC women at initial diagnosis. METHODS: 1731 Chinese early-stage BC women at initial diagnosis underwent thyroid ultrasound and 1:1 age-matched Chinese healthy women underwent health examination in corresponding period were enrolled for analysis. RESULTS: Prevalence of TN and TI-RADS ≥ 4 TN in BC patients (56.27% and 9.76%) were higher than healthy people (46.04% and 5.49%), respectively, P < 0.001. Among BC patients, prevalence of TN and TI-RADS ≥ 4 TN in hormone receptor (HR)-positive patients (59.57% and 11.81%) were higher than HR-negative patients (48.77% and 5.10%), respectively, P < 0.001, while without difference between HR-negative patients and healthy people. After adjusting for age and BMI, HR-positive patients had higher risk of TN (OR = 1.546, 95%CI 1.251-1.910, P < 0.001) and TI-RADS ≥ 4 TN (OR = 3.024, 95%CI 1.943-4.708, P < 0.001) than HR-negative patients. Furthermore, the risk of TI-RADS ≥ 4 TN was higher in patients with estrogen receptor (ER) positive (OR = 2.933, 95%CI 1.902-4.524), progesterone receptor (PR) positive (OR = 1.973, 95%CI 1.378-2.826), Ki-67 < 20% (OR = 1.797, 95%CI 1.280-2.522), and tumor size < 2 cm (OR = 1.804, 95%CI 1.276-2.552), respectively, P < 0.001. CONCLUSIONS: Prevalence of TN, especially TI-RADS ≥ 4 TN, in Chinese early-stage BC women was higher than healthy people. HR-positive patients had higher prevalence and risk of TN, while without difference between HR-negative patients and healthy people. The increased risk of TN was correlated with ER-positive, PR-positive, lower Ki-67 expression, and smaller tumor size.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Evaluating Efficacy and Safety of Tacrolimus Treatment in Membranous Nephropathy: Results of a Retrospective Study of 182 Patients.

Purpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN. Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus. Results: The mean follow-up period was 27.3 (19.3-41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids. Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study.

INTRODUCTION: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. METHODS: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. RESULTS: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. CONCLUSIONS: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Dynamics Tracking.

Background: Little is known about the dynamics of SARS-CoV-2 antigen burden in respiratory samples in different patient populations at different stages of infection. Current rapid antigen tests cannot quantitate and track antigen dynamics with high sensitivity and specificity in respiratory samples. Methods: We developed and validated an ultra-sensitive SARS-CoV-2 antigen assay with smartphone readout using the Microbubbling Digital Assay previously developed by our group, which is a platform that enables highly sensitive detection and quantitation of protein biomarkers. A computer vision-based algorithm was developed for microbubble smartphone image recognition and quantitation. A machine learning-based classifier was developed to classify the smartphone images based on detected microbubbles. Using this assay, we tracked antigen dynamics in serial swab samples from COVID patients hospitalized in ICU and immunocompromised COVID patients. Results: The limit of detection (LOD) of the Microbubbling SARS-CoV-2 Antigen Assay was 0.5 pg/mL (10.6 fM) recombinant nucleocapsid (N) antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs, comparable to many rRT-PCR methods. The assay had high analytical specificity towards SARS-CoV-2. Compared to EUA-approved rRT-PCR methods, the Microbubbling Antigen Assay demonstrated a positive percent agreement (PPA) of 97% (95% confidence interval (CI), 92-99%) in symptomatic individuals within 7 days of symptom onset and positive SARS-CoV-2 nucleic acid results, and a negative percent agreement (NPA) of 97% (95% CI, 94-100%) in symptomatic and asymptomatic individuals with negative nucleic acid results. Antigen positivity rate in NP swabs gradually decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity of the same samples. The computer vision and machine learning-based automatic microbubble image classifier could accurately identify positives and negatives, based on microbubble counts and sizes. Total microbubble volume, a potential marker of antigen burden, correlated inversely with Ct values and days-after-symptom-onset. Antigen was detected for longer periods of time in immunocompromised patients with hematologic malignancies, compared to immunocompetent individuals. Simultaneous detectable antigens and nucleic acids may indicate the presence of replicating viruses in patients with persistent infections. Conclusions: The Microbubbling SARS-CoV-2 Antigen Assay enables sensitive and specific detection of acute infections, and quantitation and tracking of antigen dynamics in different patient populations at various stages of infection. With smartphone compatibility and automated image processing, the assay is well-positioned to be adapted for point-of-care diagnosis and to explore the clinical implications of antigen dynamics in future studies.

Methylophiopogonanone A, an Ophiopogon homoisoflavonoid, alleviates high-fat diet-induced hyperlipidemia: assessment of its potential mechanism.

Methylophiopogonanone A (MO-A), a homoisoflavonoid extracted from Ophiopogon japonicus, has been shown to attenuate myocardial apoptosis and improve cerebral ischemia/reperfusion injury. However, the hypolipidemic effects remain unknown. This study was performed to investigate a potential hypolipidemic effect of MO-A in hyperlipidemia rats, as well as its underlying mechanism of action. A rat model of hyperlipidemia was induced by a high-fat diet (HFD). Animals were randomly divided into three groups (n=8/group): normal control group (NC), HFD group, and HFD+MO-A (10 mg·kg-1·d-1) treatment group. The effects of MO-A on serum lipids, body weight, activity of lipoprotein metabolism enzyme, and gene expression of lipid metabolism were evaluated in HFD-induced rats. In HFD-induced rats, pretreatment with MO-A decreased the body weight gain and reduced serum and hepatic lipid levels. In addition, pretreatment with MO-A improved the activities of lipoprotein lipase and hepatic lipase in serum and liver, down-regulated mRNA expression of acetyl CoA carboxylase and sterol regulatory element-binding protein 1c, and up-regulated mRNA expression of low-density lipoprotein receptor and peroxisome proliferator-activated receptor α in the liver. Our results indicated that MO-A showed strong ability to ameliorate the hyperlipidemia in HFD-induced rats. MO-A might be a potential candidate for prevention of overweight and dyslipidemia induced by HFD.

Development and Clinical Validation of a Sensitive Lateral Flow Assay for Rapid Urine Fentanyl Screening in the Emergency Department.

BACKGROUND: Rapid identification of fentanyl at the point-of-care is critical. Urine fentanyl concentrations in overdose cases start at single-digit nanograms per milliliter. No fentanyl point-of-care assay with a cutoff at single-digit nanograms per milliliter is available. METHODS: A competitive lateral flow assay (LFA) was developed using gold nanoparticles and optimized for rapid screening of fentanyl in 5 minutes. Urine samples from 2 cohorts of emergency department (ED) patients were tested using the LFA and LC-MS/MS. The 2 cohorts consisted of 218 consecutive ED patients with urine drug-of-abuse screen orders and 7 ED patients with clinically suspected fentanyl overdose, respectively. RESULTS: The LFA detected fentanyl (≥1 ng/mL) and the major metabolite norfentanyl (≥10 ng/mL) with high precision. There was no cross-reactivity with amphetamine, cocaine, morphine, tetrahydrocannabinol, methadone, buprenorphine, naloxone, and acetaminophen at 1000 ng/mL and 0.03%, 0.4%, and 0.05% cross-reactivity with carfentanil, risperidone, and 9-hydroxyrisperidone, respectively. In 218 consecutive ED patients, the prevalence of cases with fentanyl ≥1 ng/mL or norfentanyl ≥10 ng/mL was 5.5%. The clinical sensitivity and specificity of the LFA were 100% (95% CI, 75.8-100%) and 99.5% (95% CI, 97.3-99.9%), respectively. The positive and negative predictive values were 92.3% (95% CI, 66.7-98.6%) and 100% (95% CI, 98.2-100%), respectively. The concordance between the LFA and LC-MS/MS was 100% in the 7 suspected fentanyl overdose cases (5 positive, 2 negative). CONCLUSIONS: The LFA can detect fentanyl and norfentanyl with high clinical sensitivity and specificity in the ED population with rapid fentanyl screening needs.

Methylophiopogonanone A, an Ophiopogon homoisoflavonoid, alleviates high-fat diet-induced hyperlipidemia: assessment of its potential mechanism

Methylophiopogonanone A (MO-A), a homoisoflavonoid extracted from Ophiopogon japonicus, has been shown to attenuate myocardial apoptosis and improve cerebral ischemia/reperfusion injury. However, the hypolipidemic effects remain unknown. This study was performed to investigate a potential hypolipidemic effect of MO-A in hyperlipidemia rats, as well as its underlying mechanism of action. A rat model of hyperlipidemia was induced by a high-fat diet (HFD). Animals were randomly divided into three groups (n=8/group): normal control group (NC), HFD group, and HFD+MO-A (10 mg·kg-1·d-1) treatment group. The effects of MO-A on serum lipids, body weight, activity of lipoprotein metabolism enzyme, and gene expression of lipid metabolism were evaluated in HFD-induced rats. In HFD-induced rats, pretreatment with MO-A decreased the body weight gain and reduced serum and hepatic lipid levels. In addition, pretreatment with MO-A improved the activities of lipoprotein lipase and hepatic lipase in serum and liver, down-regulated mRNA expression of acetyl CoA carboxylase and sterol regulatory element-binding protein 1c, and up-regulated mRNA expression of low-density lipoprotein receptor and peroxisome proliferator-activated receptor α in the liver. Our results indicated that MO-A showed strong ability to ameliorate the hyperlipidemia in HFD-induced rats. MO-A might be a potential candidate for prevention of overweight and dyslipidemia induced by HFD.

Programmed cell death 5 transgenic mice attenuates adjuvant induced arthritis by 2 modifying the T lymphocytes balance.

BACKGROUND: Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice. RESULTS: In the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4+IFN-γ+ cells (Th1) and CD4+IL-17A+ cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4+CD25+Foxp3+ regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4. CONCLUSIONS: Based on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.

Programmed cell death 5 transgenic mice attenuates adjuvant induced arthritis by 2 modifying the T lymphocytes balance

BACKGROUND: Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice. RESULTS: In the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4+IFN-γ+ cells (Th1) and CD4+IL-17A+ cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4+CD25+Foxp3+ regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4. CONCLUSIONS: Based on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.