Sedentary behavior is associated with chronic obstructive pulmonary disease: A generalized propensity score-weighted analysis

Chronic obstructive pulmonary disease (COPD) is the fourth and third leading cause of death worldwide and in China, respectively. Sedentary behavior has been shown to increase the risk of respiratory disease, such as asthma. However, the relationship between sedentary behavior and COPD is unclear. This study aimed to investigate the association between sedentary behavior and COPD.Data was extracted from the 2018 a large-scale cross-sectional study of Chronic Disease and Lifestyle Population Survey in Sichuan Province of China, in which sedentary behavior and chronic diseases were self-reported according to medical records. The association between sedentary behavior on risk of COPD was estimated using multivariable regression model in non-matching cohorts and generalized propensity score-weighted (GPSW)cohorts, respectively, controlling for potential confounders.Individuals who remained sedentary for more than 7 hours per day were more likely to have COPD than the control group (<3 hours) both in conventional multivariate logistic regression analysis (OR = 2.020, 95%CI: 1.575–2.585, P < .001) and GPSW analysis (OR = 2.381, 95%CI: 1.778–3.188, P < .001). After GPSW and the sensitivity analysis using refined smoking variable further found a dose-effect between sedentary behavior and COPD, with 1.242 (95%CI: 1.006–1.532, P < .05) times risk of COPD in those sedentary behavior of more than 5 hours per day (GPSW) and 1.377 (95%CI: 1.092–1.736, P < .05) times risk in those sedentary behavior above 5 hours per day (sensitivity analysis), comparing with the control group.Sedentary behavior is independently associated with increased risk of COPD, adjusting for other confounders. The findings of this study have important implications for future research and public health guidance. Reducing sedentary time may have a significant role in COPD prevention.     

Measurement of Free Versus Total Therapeutic Monoclonal Antibody in Pharmacokinetic Assessment is Modulated by Affinity,Incubation Time,and Bioanalytical Platform

Decisions about efficacy and safety of therapeutic proteins (TP) designed to target soluble ligands are made in part by their ex vivo quantification. Ligand binding assays (LBAs) are critical tools in measuring serum TP levels in pharmacokinetic, toxicokinetic, and pharmacodynamic studies. This study evaluated the impact of reagent antibody affinities, assay incubation times, and analytical platform on free or total TP quantitation. An ELISA-based LBA that measures monoclonal anti-sclerostin antibody (TPx) was used as the model system. To determine whether the method measures free or total TPx, the effects of K_on, K_off, and K_D were determined. An 8:1 molar ratio of sclerostin (Scl) to TPx compared to a 1:1 molar ratio produced by rabbit polyclonal antibodies to TPx was required to achieve IC₅₀, a measure of TPx interference effectiveness, making it unclear whether the ELISA truly measured free TPx. Kinetic analysis revealed that Scl had a rapid dissociation rate (K_off) from TPx and that capture and detection antibodies had significantly higher binding affinities (K_D) to TPx. These kinetic limitations along with long ELISA incubation times lead to the higher molar ratios (8:1) required for achieving 50% inhibition of TPx. However, a microfluidic platform with the same reagent pairs required shorter incubations to achieve a lower Scl IC₅₀ molar ratio (1:1). The findings from this study provide the bioanalytical community with a deeper understanding of how reagent and platform selection for LBAs can affect what a particular method measures, either free or total TP concentrations.KEY WORDS: affinity and kinetics, association and dissociation, free versus total, interference, ligand binding assay     

Therapeutic effects of puerarin on polycystic ovary syndrome: A randomized trial in Chinese women

Background:This study aims to assess the therapeutic effects of a well-known component (puerarin) obtained from a Chinese herb root in patients with polycystic ovary syndrome (PCOS).Methods:Women with premature ovarian failure (POF) were assigned to the obese group (body mass index [BMI] ≥24 kg/m² and waist hip ratio [WHR] >0.85) or non-obese group (group 3, n = 21). Obese patients were further randomly assigned to the obese treatment group (group 1, n = 15) and obese control group (group 1, n = 15). All patients received standard treatment (Diane-35, 1 tablet/d, orally, plus metformin, 1.5 g/d, orally). In addition to the standard modality, patients in group 1 and group 3 also orally received 150 mg/d of puerarin tablets for 3 months. Venous blood was drawn before and after treatment. Then, the metabolic and antioxidant biomarkers were measured. The normality of distribution of the data was tested using the Kolmogorov–Smirnov method. The baseline characteristics were analyzed using one-factor analysis of variance (ANOVA), and post-hoc was performed using the least significance difference (LSD)-t test.Results:Significantly improved blood levels of sex hormone binding globulin (SHBG) and superoxide dismutase (SOD) were observed in patients who received the additional treatment of puerarin, regardless of their lean or obese status, while these were not observed in patients who did not receive puerarin. Furthermore, obese patients with PCOS had significantly lower systolic blood pressure, total cholesterol, and testosterone blood levels, when compared with before treatment.Conclusion:The addition of puerarin to the present treatment protocol can be considered for the management of metabolic disorders and hyperandrogenism in PCOS patients.     

Gastric adenocarcinoma of fundic gland (chief cell predominant type) coexisting with well differentiated intestinal adenocarcinoma: A case report

Rationale:Gastric adenocarcinoma of fundic gland (chief cell predominant type) (GA-FG-CCP) is a new, rare variant of gastric adenocarcinoma, which is characterized by mild nuclear atypia and specific immunohistochemical markers.Patient concerns:An 84-year-old Chinese man was referred to our hospital for endoscopic resection of a gastric lesion.Interventions:We performed endoscopic submucosal dissection, and successfully removed the lesion.Diagnosis:Esophago gastroduodenoscopy showed a slightly elevated lesion with a diameter of 22 mm in the posterior wall of cardia. Magnifying endoscopy with narrow band imaging revealed an abnormal microsurface and microvessels on the tumor surface. Endoscopic ultrasonography revealed a hypoechoic mass located in the first layer. The pathological diagnosis of the biopsy specimens indicated that the tumor was high grade intraepithelial neoplasia. The pathological diagnosis differed between the superficial and deeper part of the lesion. The superficial part was composed of a tubular structure with prominent atypia and was diagnosed as well differentiated intestinal adenocarcinoma. The deeper part was composed of a well-differentiated tubular adenocarcinoma mimicking the fundic gland cells, mainly the chief cells. The tumor cells showed mild nuclear atypia and was positive for pepsinogen-I (PG-I) and mucin-6 (MUC6). This deeper part was diagnosed as GA-FG-CCP.Outcomes:The tumor was successfully removed. This patient had no discomfort during the follow-up period (10 months).Lessons:We present a rare case of GA-FG-CCP coexisted with well-differentiated tubular adenocarcinoma. GA-FG-CCP exists in the deep mucosal layer and the muscularis mucosa, which could not be found under endoscopy, but could be discerned in pathology with mild nuclear atypia and special biomarkers.     

Early-life educational attainment,APOE ε4 alleles,and incident dementia risk in late life

GeroScience - We examined the interactions between educational attainment and genetic susceptibility on dementia risk among adults over 60&nbsp;years old. A total of 174,161 participants were...     

Increased Risk of Infections with Anti-TNF Agents in Patients with Crohn’s Disease After Elective Surgery: Meta-Analysis

Digestive Diseases and Sciences - Postoperative complication rates in patients with inflammatory bowel disease (IBD) receiving preoperative biologics have been analyzed without considering the...     

An Efficient Approach for Automated Mass Segmentation and Classification in Mammograms

Breast cancer is becoming a leading death of women all over the world; clinical experiments demonstrate that early detection and accurate diagnosis can increase the potential of treatment. In order to improve the breast cancer diagnosis precision, this paper presents a novel automated segmentation and classification method for mammograms. We conduct the experiment on both DDSM database and MIAS database, firstly extract the region of interests (ROIs) with chain codes and using the rough set (RS) method to enhance the ROIs, secondly segment the mass region from the location ROIs with an improved vector field convolution (VFC) snake and following extract features from the mass region and its surroundings, and then establish features database with 32 dimensions; finally, these features are used as input to several classification techniques. In our work, the random forest is used and compared with support vector machine (SVM), genetic algorithm support vector machine (GA-SVM), particle swarm optimization support vector machine (PSO-SVM), and decision tree. The effectiveness of our method is evaluated by a comprehensive and objective evaluation system; also, Matthew’s correlation coefficient (MCC) indicator is used. Among the state-of-the-art classifiers, our method achieves the best performance with best accuracy of 97.73 %, and the MCC value reaches 0.8668 and 0.8652 in unique DDSM database and both two databases, respectively. Experimental results prove that the proposed method outperforms the other methods; it could consider applying in CAD systems to assist the physicians for breast cancer diagnosis.     

Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5

In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed “Mendelian vascular diseases,” which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types.     

Relationship between human leukocyte antigen-DRB1 and autoimmune hepatitis type I in Chinese patients

AIM: To analyze the association of human leukocyte antigen (HLA)-DRB1 with autoimmune hepatitis type I (AIH) among Chinese patients in the Shanghai area. METHODS: In 32 patients and 48 healthy controls, polymerase chain reaction amplified with sequence-specific primers (PCR-SSP) was performed to elucidate the relevance of certain alleles or polymorphic sequences of HLA-DRB1 with autoimmune hepatitis. RESULTS: The HLA-DRB1 typing by PCR-SSP showed that DR4 had a significantly increased frequency among patients with AIH versus that of healthy controls (46.9 vs 20.8%; relative risk = 3.35, P = 0.014). In the subtypes of DR4, there was a trend of an increase in the gene frequency of DRB1*0405 in patients with AIH versus that of healthy controls (21.9 vs 6.3%, P = 0.04, but corrected P (Pc) = 0.08). In addition, our analysis indicated a significant increase in the alleles frequency encoding Leu-Leu-Glu-Gln-Lys-Arg (LLEQRR) from the third hyperpolymorphic region (HVR3) of DR4 in the patients with AIH (86.7% of DR4 positive patients vs 40.0% in DR4 positive controls, P = 0.016, Pc = 0.028, relative risk (RR) = 9.75). CONCLUSION: Type I AIH among Chinese patients is associated with HLA-DR4. There is a relevance of type I AIH and LLEQRR sequence within the third hyperpolymorphic region of the DRB1 allele.