Influencing factors of delay in seeking medical attention of patients with obstructive sleep apnea based on the Model of Pathways to Treatment in China: a qualitative analysis.

BACKGROUND: There is the highest estimated number of patients with obstructive sleep apnea (OSA) in China. Early treatment could lead to fewer complications associated with OSA. This study aimed to analyze the factors influencing help-seeking from the first symptom discovery to treatment in OSA. METHODS: Semi-structured interview outline was designed to conduct face-to-face interview based on the analyses of a great number of related literatures on the delay in seeking medical attention of patients with OSA. 15 patients diagnosed were interviewed between June 2021 to September 2022 in general hospital of Shenyang, Northeastern of China. Qualitative data was analyzed by content analysis using the Model of Pathways to Treatment. RESULTS: Analyses identified factors contributing to elapsed time from first symptom discovery to received treatment that are linked to disease characteristic, patients, health system organization. Appraisal interval is most obvious for patients with OSA, but it is difficult to pinpoint precisely because the patients didn't remember exactly when the first symptom was detected. CONCLUSIONS: Patients diagnosed with OSA didn't initially interpret the snore as a warning sign and even thought it was a blessing. The findings provided guidance or avenues for reducing elapsed time between the first symptom and received treatment.

A novel microfluidic chip-based digital PCR method for enhanced sensitivity in the early diagnosis of colorectal cancer via mSEPT9.

BACKGROUND: To enhance the sensitivity of plasma methylated Septin9 gene (mSEPT9) detection in colorectal cancer (CRC) screening, we developed a microfluidic chip-based digital PCR (dPCR) method suitable for low-concentration samples, aiming to apply it for mSEPT9 detection in CRC diagnosis. METHODS: Our microfluidic chip-based dPCR method utilized specific primers and probes with locked nucleic acids (LNAs) modifications for mSEPT9 detection. We evaluated its performance, including detection limit, specificity, and linear range, comparing it with a commercial qPCR reagent kit using the same samples (95 CRC, 23 non-CRC). RESULTS: The LNAs-modified dPCR method showed a linear range of 100-104 copies/µL and a detection limit of 100 copies/µL. Clinical testing revealed that our dPCR method exhibited a sensitivity of 82.11 % and specificity of 95.65 % for CRC diagnosis, outperforming the commercial qPCR kit (sensitivity: 58.95 %, specificity: 91.30 %), particularly in Stage I with a diagnostic sensitivity of 90.91 %. Combining mSEPT9 and carcinoembryonic antigen (CEA) improved diagnostic sensitivity to 91.49 %. CONCLUSIONS: Our accurate microfluidic chip-based dPCR method, especially in combination with CEA, holds promise for effective CRC screening and timely interventions, offering enhanced mSEPT9 quantification over conventional qPCR.

A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population.

BACKGROUND: CD40 is an important immune costimulatory molecule that has recently been found to be associated with chronic hepatitis B. This study aims to explore the association between CD40 polymorphisms and HBV infection, as well as to investigate the impact of different rs1883832 genotypes on CD40 expression and its effect on the progression of chronic HBV infection. METHODS: We genotyped rs1883832 in 3433 individuals using MassARRAY, and quantified the CD40 expression, including CD40 mRNA, sCD40, and mCD40. The CD40 and HBV infection indicators were assessed to investigate the potential function of rs1883832 in suppressing HBV replication in HepG2.2.15 and HepAD38, CD40L in cytotoxic t lymphocytes (CTLs) and interferon-γ, TNF-α, granzyme B, and perforin were measured to elucidate the mechanism by which CD40 inhibits HBV replication. RESULTS: Our study revealed that the frequencies of CC genotype and C allele of rs1883832 were significantly higher in immune recovery compared to chronic hepatitis B. Individuals with CC genotype exhibited significantly elevated CD40 in serum and B cells compared to TT genotypes in chronic hepatitis B. Additionally, CD40 is capable of inhibiting HBV replication and transcription in hepatocytes by means of interaction with CD40L. A significant negative correlation was found between HBV DNA, HBeAg, and mCD40. Conversely, the expressions of ALT and mCD40 showed a positive correlation, which aligns with the trend of CD40L. CONCLUSIONS: rs1883832 C allele may have a protective role in HBV immune recovery. This protective effect could potentially be attributed to the regulation of CD40 expression. The activation of the anti-HBV immune response, which occurs through binding CD40L on CTL, can suppress HBV DNA replication and potentially facilitate immune recovery in HBV infection.

Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Using machine learning models to predict HBeAg seroconversion in CHB patients receiving pegylated interferon-α monotherapy.

BACKGROUND AND OBJECTIVE: Though there are many advantages of pegylated interferon-α (PegIFN-α) treatment to chronic hepatitis B (CHB) patients, the response rate of PegIFN-α is only 30 ~ 40%. Therefore, it is important to explore predictors at baseline and establish models to improve the response rate of PegIFN-α. METHODS: We randomly divided 260 HBeAg-positive CHB patients who were not previously treated and received PegIFN-α monotherapy (180 µg/week) into a training dataset (70%) and testing dataset (30%). The intersect features were extracted from 50 routine laboratory variables using the recursive feature elimination method algorithm, Boruta algorithm, and Least Absolute Shrinkage and Selection Operator Regression algorithm in the training dataset. After that, based on the intersect features, eight machine learning models including Logistic Regression, k-Nearest Neighbors, Support Vector Machine, Decision Tree, Random Forest, Gradient Boosting, Extreme Gradient Boosting (XGBoost), and Naïve Bayes were applied to evaluate HBeAg seroconversion in HBeAg-positive CHB patients receiving PegIFN-α monotherapy in the training dataset and testing dataset. RESULTS: XGBoost model showed the best performance, which had largest AUROC (0.900, 95% CI: 0.85-0.95 and 0.910, 95% CI: 0.84-0.98, in training dataset and testing dataset, respectively), and the best calibration curve performance to predict HBeAg seroconversion. The importance of XGBoost model indicated that treatment time contributed greatest to HBeAg seroconversion, followed by HBV DNA(log), HBeAg, HBeAb, HBcAb, ALT, triglyceride, and ALP. CONCLUSIONS: XGBoost model based on common laboratory variables had good performance in predicting HBeAg seroconversion in HBeAg-positive CHB patients receiving PegIFN-α monotherapy.

Adenosine Triphosphate in Serum as a Promising Biomarker for Differential Diagnosis of Hepatitis B Disease Progression.

The need to be diagnosed with liver biopsy makes the clinical progression of chronic HBV infection diagnosis a challenge. Existing HBV serum biochemical assays are used throughout clinical but have limited effects. Studies have shown that mitochondrial function is tightly coupled to HBV infection. Here, we verified the diagnostic value of serum Adenosine Triphosphate (ATP) as a potential marker for differential HBV infection progress by detecting the level of ATP in the serum from a wide spectrum of HBV-infected populations, and confirmed the role of ATP in the deterioration of HBV infection-related diseases through HBV-infected cells and mouse models. The results showed that there were significantly lower serum ATP levels in HBeAg-positive CHB patients compared with healthy controls. And during the progression of CHB to liver cirrhosis and hepatocellular carcinoma, the ATP level was increased but not higher than healthy controls. The area under the curve (AUC) of serum ATP was 0.9063 to distinguish HBeAg-positive CHB from healthy, and another AUC was 0.8328 in the CHB against the HCC group. Preliminary exploration of the mechanism indicated that the decline of serum ATP was due to impaired mitochondria in CHB patients. Our data provide evidence that serum ATP distinguishes the various progress of HBV infection-related diseases and expands diagnostic biomarkers for HBeAg-positive CHB patients with healthy controls.

Severity distribution and treatment of chronic obstructive pulmonary disease in China: baseline results of an observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) receives low awareness and is undertreated in China. Understanding the burden and treatment of COPD across the nation is important for improving quality of care for this disease. This study aims to reveal the current situation of COPD severity distribution and management across China. METHODS: Baseline data from REALizing and Improving Management of Stable COPD in China, a multicentre, prospective, longitudinal, observational study, were analysed. Patients diagnosed with COPD as per Global Initiative for Chronic Obstructive Lung Disease 2016 (GOLD 2016) criteria were enrolled from 50 randomly selected hospitals (tertiary, 25; secondary, 25) across six geographical regions. Data were collected in routine clinical settings. RESULTS: Between 15 December 2017 and 6 August 2020, 5013 patients were enrolled and 4978 included in the full analysis set. Of these, 2459 (49.4%) reported ≥ 1 exacerbation within 12 months prior to study enrolment, with a mean annual rate of 0.9/patient, including 0.2/patient and 0.5/patient leading to emergency room visits and hospitalisation, respectively. Spirometry graded 458 (10.1%), 1886 (41.7%), 1558 (34.5%), and 616 (13.6%) were GOLD stage I-IV, and 536 (11.4%), 1034 (22.0%), 563 (12.0%), and 2566 (54.6%) were classified as GOLD 2016 Group A-D, respectively, without evident regional variations. Inhaled corticosteroids plus long-acting beta2-agonist (ICS/LABA, 1316 [26.4%]), ICS/LABA plus long-acting muscarinic antagonist (ICS/LABA + LAMA, 871 [17.5%]), and LAMA (754 [15.1%]) were prescribed at high rates across all groups and regions. Medications not recommended by GOLD were commonly prescribed (TCM, 578 [11.6%]; others, 951 [19.1%]), and 681 (13.7%) were not given ICS or long-acting bronchodilators. CONCLUSIONS: Disease burden among Chinese COPD outpatients is high. Improved guideline adherence for COPD treatment is needed. Trial registration ClinicalTrials.gov identifier, NCT03131362.

Combination of Theoretical and Experimental Insights into the Oxygenated Fuel Poly(oxymethylene) Dibutyl Ether from n-Butanol and Paraformaldehyde.

Oxygenated fuel has the function of self-supplying oxygen during the combustion process, which can greatly improve emission performance and reduce diesel fuel soot production. In this paper, a novel oxygenated fuel poly(oxymethylene) dibutyl ether (PODBE n ) is designed and synthesized through experiments in combination with density functional theory (DFT) calculation. The experimental results show that PODBE n has the advantages of high cetane number (73.6), moderate density (868 kg/m3), and low condensation point (-72 °C). According to the DFT calculation results, the molecular (PODBE n ) polarity index of different polymerization degrees is similar to the value of diesel and has good mutual solubility with diesel. Moreover, the mechanism of the entire path of synthesis is calculated at the M06-2X/6-311G(d,p) level of theory. The energetic profile reveals that the rate-determining step is the nucleophilic addition step with the highest barrier energy (TS1 = 21.59 kcal/mol). This work provides a feasible method to synthesize high-performance oxygenated fuel PODBE n using NKC-9 ion-exchange resins.

Extractive removal of micro and trace nitrofen, 2, 4-dichlorophenol and p-nitrotrophenol from water/soil by humic acid ester ether.

The amphiphilic humic acid ester ether (HAEE), as a kind of solid-phase extractant with characteristics of easy separation and hydrophilic-hydrophobic amphiphilic property, was prepared and used to extract micro or trace nitrofen, 2,4-dichlorophenol and p-nitrotrophenol (NIPs) from water and soil. Degradation of NIPs and extractant regeneration were carried out by simple photocatalysis. The adsorption equilibrium of the mono- or three mixed NIPs by HAEE in aqueous could be quickly reached within 20 min. The adsorption process was fit to quasi-second-order kinetics model and Friendlich thermodynamics model. The possible adsorption interaction was discussed. Results suggested that the adsorption of NIPs onto HAEE predominated by hydrogen bonding, hydrophobic interaction and π-π interaction. The extraction capacity of mixed NIPs (80 µg/L each component) by HAEE was up to 0.38 mg/g and tended to be multi-layer adsorption, in which p-nitrotrophenol had higher adsorption competitiveness because of lower resistance to HAEE. When HAEE-NIPs were degraded by photo-catalyst Fe0/F-TiO2 for 8 h, not only the adsorbed NIPs could be totally degraded and mineralized, but also the HAEE could be effectively regenerated. When the NIPs were continuously extracted from 40-year aging soil for three times (regenerative twice) by combined extractant (48 mL H2O + 2 mL n-hexane + 0.1 g HAEE), the total extraction efficiency of NIPs could reach to 84.66%. This research could supplement the theory and technique for harmless treatment of NIPs contaminated water and soil.

Taurocholic acid inhibits the response to interferon-α therapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8+ T and NK cell function.

Pegylated interferon-alpha (PegIFNα) therapy has limited effectiveness in hepatitis B e-antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. However, the mechanism underlying this failure is poorly understood. We aimed to investigate the influence of bile acids (BAs), especially taurocholic acid (TCA), on the response to PegIFNα therapy in CHB patients. Here, we used mass spectrometry to determine serum BA profiles in 110 patients with chronic HBV infection and 20 healthy controls (HCs). We found that serum BAs, especially TCA, were significantly elevated in HBeAg-positive CHB patients compared with those in HCs and patients in other phases of chronic HBV infection. Moreover, serum BAs, particularly TCA, inhibited the response to PegIFNα therapy in HBeAg-positive CHB patients. Mechanistically, the expression levels of IFN-γ, TNF-α, granzyme B, and perforin were measured using flow cytometry to assess the effector functions of immune cells in patients with low or high BA levels. We found that BAs reduced the number and proportion and impaired the effector functions of CD3+CD8+ T cells and natural killer (NK) cells in HBeAg-positive CHB patients. TCA in particular reduced the frequency and impaired the effector functions of CD3+CD8+ T and NK cells in vitro and in vivo and inhibited the immunoregulatory activity of IFN-α in vitro. Thus, our results show that BAs, especially TCA, inhibit the response to PegIFNα therapy by impairing the effector functions of CD3+CD8+ T and NK cells in HBeAg-positive CHB patients. Our findings suggest that targeting TCA could be a promising approach for restoring IFN-α responsiveness during CHB treatment.

Mechanistic insights into the C-H activation of methane mediated by the unsupported and silica-supported VO2OH and CrOOH: a DFT study.

The direct activation and conversion of methane has been a topic of interest in both academia and industry for several decades. Deep understanding of the corresponding mechanism and reactivity mediated by diverse catalytic clusters, as well as the supporting materials, is still highly desired. In this work, the regulation mechanism of C-H bond activation of methane, mediated by the closed-shell VO2OH, the open-shell CrOOH, and their silica supported clusters, has been investigated by density functional theory (DFT) calculations. The hydrogen-atom transfer (HAT) reaction towards methane C-H bond activation is more feasible when mediated by the unsupported/silica-supported CrOOH clusters versus the VO2OH clusters, due to the intrinsic spin density located on the terminal Ot atom. The proton-coupled electron transfer (PCET) pathways are regulated by both the nucleophilicity of the Ot site and the electrophilicity of the metal center, which show no obvious difference in energy consumption among the four reactions examined. Moreover, the introduction of a silica support can lead to subtle influences on the intermolecular interaction between the CH4 molecule and the catalyst cluster, as well as the thermodynamics of the methane C-H activation.

IL-17 and IL-21 polymorphisms in relation to HBV related hepatocellular carcinoma in Chinese Han population.

OBJECTIVE: Inflammatory cytokine gene polymorphisms may influence the hepatic and extrahepatic HBV-related disease. In this study, we aimed to investigate the relationship between polymorphisms of IL-17, IL-21 gene and HBV related hepatocellular carcinoma in Chinese Han population. METHODS: We performed a multi-center study comprised 866 HBV-related hepatocellular carcinoma (HCC) patients and 1086 unrelated patients with a diagnosis of chronic hepatitis B (CHB) as control to evaluate the effects of IL-17 (rs4711998), IL-21 SNPs (rs12508721, rs13143866 and rs2221903) and the susceptibility of HCC. MassARRAY technology was utilized to genotype. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IL-17 and IL-21 level. Quantitative real time polymerase chain reaction (qRT-PCR) was used to analyze the serum viral loads. RESULTS: In logistic regression analysis, our results showed the frequency of rs4711998 allele G in CHB group was significantly higher than that in HCC group (P = 0.042, 0.859(0.743-0.994)), and it is present only among females. Compared to HCC group, rs13143866 A allele was more likely to appear in HCC group (P = 0.015, 1.268 (1.049-1.532)). The frequency of AA also showed different between HCC group and CHB groups (P = 0.011, 3.135 (1.292-7.603)), which showed strong sex-specific relationships. ELISA showed a higher serum IL-17 and IL-21 expression in HCC patients compared to CHB patients (P all <0.05). Haplotype rs12508721C/rs13143866A/rs2221903T in male HCC group was statistically higher than in male CHB group(P = 0.013) but not in females (P > 0.05). CONCLUSION: We suggested rs4711998 allele A as risk factors for women to develop HBV related-HCC in Chinese Han population. rs13143866 allele A as risk factors to develop HBV related-HCC in Chinese male population. Male patients with haplotype rs12508721C/rs13143866A/rs2221903T may with 1.3-fold risk for HBV-related HCC.

Association Between Adherence to Maintenance Medication in Patients with COPD and Acute Exacerbation Occurrence and Cost in China: A Retrospective Cohort Database Study.

Background: This study aimed to evaluate the association between adherence to maintenance medication (ie, inhaled bronchodilators, inhaled corticosteroid/long-acting beta-2 agonist [ICS/LABA] combinations, and oral therapy) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and related costs among patients with chronic obstructive pulmonary disease (COPD) in China. Patients and Methods: Claims data from the hospitals of a metropolitan city in south China between January 2014 and December 2016 were obtained. Patients with COPD with ≥2 maintenance medication claims during 1 year were included. Adherence was measured by the proportion of days covered (PDC). The interaction of medication class×adherence was considered when building models. Results: A total of 11,708 patients met the inclusion criteria, of whom 10.8% were highly adherent (PDC≥0.8). There were significant interaction effects of drug category on hospitalized AECOPD risk (P≤0.001), hospitalized AECOPD rate (P<0.001), and 1-year hospitalized AECOPD treatment costs (P=0.012). There was a relationship between high adherence and outcomes for ICS/LABA combinations (n=3,419), ie, relative risk of hospitalized AECOPD was reduced by 34.8% (adjusted odds ratio=0.65; 95% confidence interval (CI): 0.54-0.79; P<0.001) while the frequency of hospitalized AECOPD per patient-year was reduced by 24.4% (adjusted rate ratio=0.76; 95% CI: 0.65 to 0.87; P<0.001). Mean 1-year per-patient hospitalized AECOPD costs were reduced by 37.8% (mean difference=-848 USD; 95% CI: -1435-262 USD; P<0.001). Patients taking oral mucolytics and having high adherence had worse AECOPD outcomes than patients with poor adherence. Conclusion: High adherence to ICS/LABA maintenance therapy was associated with reduced hospitalized AECOPD rates and costs in Chinese patients with COPD.

REALizing and improving management of stable COPD in China: a multi-center, prospective, observational study to realize the current situation of COPD patients in China (REAL) - rationale, study design, and protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fifth leading cause of death in China with a reported prevalence of 8.2% people aged ≥40 years. It is recommended that Chinese physicians follow Global Initiative for Chronic Obstructive Lung Disease (GOLD) and national guidelines, yet many patients with COPD in China remain undiagnosed. Furthermore, missed diagnoses and a lack of standardized diagnosis and treatment remain significant problems. The situation is further complicated by a lack of large-scale, long-term, prospective studies of real-world outcomes, including exacerbation rates, disease severity, efficacy of treatment, and compliance of COPD patients in China. METHODS/DESIGN: The REALizing and improving management of stable COPD in China (REAL) study is a 52-week multi-center, prospective, observational trial. REAL aims to recruit approximately 5000 outpatients aged ≥40 years with a clinical diagnosis of COPD per GOLD 2016. Outpatients will be consecutively recruited from approximately 50 tertiary and secondary hospitals randomly selected across six geographic regions to provide a representative population. Patients will receive conventional medical care as determined by their treating physicians. The primary objective is to evaluate COPD patient outcomes including lung function, health status, exacerbations, hospitalization rate, and dyspnea following 1 year of current clinical practice. Secondary objectives are to assess disease severity, treatment patterns, adherence to medication, and associated risk factors. Data will be collected at two study visits, at patients' usual care visits, and by telephone interview every 3 months. DISCUSSION: Knowledge of COPD among physicians in China is poor. The REAL study will provide reliable information on COPD management, outcomes, and risk factors that may help improve the standard of care in China. Patient recruitment began on 30 June 2017 and the estimated primary completion date is 30 July 2019. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03131362. Registered on 20 March 2017.

Recyclable Amphiphilic Metal Nanoparticle Colloid Enabled Atmospheric Oxidation of Alcohols.

Developing amphiphilic colloid catalysts is essentially important for realizing environmentally benign biphasic catalysis under atmospheric conditions. Herein, a linear structured plant polyphenol was employed as an amphiphilic stabilizer for preparing a series of amphiphilic Pd nanoparticles (PdNPs) colloids. For the as-prepared PdNPs colloids, the phenolic hydroxyls of plant polyphenols were responsible for the stabilization of PdNPs, whereas the rigid aromatic scaffold of plant polyphenols effectively suppressed the PdNPs from aggregation by providing a high steric effect. Thanks to the coexistence of hydrophilic phenolic hydroxyls and hydrophobic aromatic rings, the plant polyphenols induced tunable amphiphilic properties into the PdNPs, allowing an easier wetting of PdNPs with the substrate molecules. By tuning the content of plant polyphenols in the colloid, the particle size (3.17-4.73 nm) and the dispersity of the PdNPs were facilely controlled. When applied for atmospheric oxidation of insoluble alcohols in water by air, the amphiphilic PdNPs preferentially absorbed the alcohol substrates to create a relatively high-substrate-concentration microenvironment, which improved the mass transfer in the biphasic catalysis, allowing the proceeding of low-temperature (50 °C) atmospheric oxidation of diverse alcohols with high catalytic conversion, including aliphatic alcohols, cyclic aliphatic alcohols, and aromatic alcohols. Furthermore, the amphiphilic PdNPs colloid also exhibited excellent reusability with a conversion yield high up to 97.96% in the fifth cycle. In contrast, the control catalysts of poly(vinylpyrrolidone)- and poly(ethylene glycol)-stabilized PdNPs were completely inactivated in the fifth cycle. As a consequence, our findings provided a new route for developing an environmentally benign aqueous colloid catalyst that is both highly active and recyclable for mild biphasic oxidation reaction systems.

Prediction value of serum HBV large surface protein in different phases of HBV infection and virological response of chronic hepatitis B patients.

BACKGROUND: Serum HBV large surface protein (HBV-LP) is an envelope protein that has a close relationship with HBV DNA level. This study is to explore the prediction value of HBV-LP in different phase of HBV infection and during antiviral therapy in chronic hepatitis B (CHB) patients. METHODS: A retrospective study was conducted in 2033 individuals, which included 1677 HBV infected patients in different phases and 356 healthy controls. HBV-LP, HBV serum markers and HBV DNA were detected by ELISA, CMIA and qRT-PCR, respectively. 85 CHB patients receiving PegIFNα or ETV were divided into virological response (VR) and partial virological response (PVR). The dynamic changes of HBV DNA and HBV-LP were observed. RESULTS: The level of HBV-LP in 2033 individuals was shown as: HBeAg-positive hepatitis > HBeAg-positive infection > HBeAg-negative hepatitis > HBeAg-negative infection > healthy controls. HBV-LP was positive in all patients whose HBV DNA > 1.0E + 06 IU/ml. When HBsAg was <0.05 IU/ml or >1000 IU/ml, HBV DNAs were all negative if HBV-LP < 1.0 S/CO. When HBsAg was between 0.05 IU/ml and 1000 IU/ml, the consistency of HBV-LP with HBV DNA was 100% in case of HBV-LP > 4.0 S/CO in HBeAg-positive patients and HBV-LP > 2.0 S/CO in HBeAg-negative ones. During antiviral therapy, baseline HBV-LP was lower in VR patients than that in PVR patients. The optimal cut-off points to predict VR by baseline HBV-LP were 32.4 and 28.6 S/CO for HBeAg-positive and HBeAg-negative hepatitis patients, respectively. CONCLUSIONS: HBV-LP may be a useful marker for distinguishing the different phases of HBV infection. Moreover, baseline HBV-LP level can be used for predicting VR of CHB patients.

Current situation of asthma-COPD overlap syndrome (ACOS) in Chinese patients older than 40 years with airflow limitation: rationale and design for a multicenter, cross-sectional trial (study protocol).

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are the frequently occurring chronic airway diseases, and the overlapping syndrome observed in the majority of patients has been recently defined as asthma-COPD overlap syndrome (ACOS) by the Global Initiative for Chronic Obstructive Lung (GOLD, 2014) and Global initiative for Asthma (GINA, 2015). The proportion, features, and clinical practice of ACOS still remain elusive in China. We are conducting this multicenter, cross-sectional, observational study (NCT02600221) to investigate the distributions of chronic obstructive diseases in patients >40 years of age with chronic airflow limitation in China along with determination of the main clinical practice and features of these diseases. The study will also explore the factors that may influence the exacerbations and severity of ACOS in Chinese patients (>40 years of age). METHODS: A total of 2,000 patients (age, ≥40 years; either sex) who are clinically diagnosed as having asthma, COPD/chronic bronchitis/emphysema, or ACOS for at least 12 months with airflow limitation [post-bronchodilator forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC): <0.7] will be enrolled from approximately 20 sites in China between December 2015 and December 2016. The proportion of ACOS among patients older than 40 years based on GINA 2015 and GOLD 2014 definitions is the primary variable. Following were the secondary variables: the proportions of COPD and asthma among the patients, distributions of the severity of airflow limitation, distribution of groups according to GOLD 2011 group definition (A, B, C, D), and the distribution of medication by drug class in patients with ACOS, asthma, and COPD. Acute exacerbation history, hospitalization, and severity of ACOS as evaluated using COPD Assessment Test, Asthma Control Questionnaire-5, and Modified British Medical Research Council in patients with ACOS were also assessed. IMPLICATIONS: This will be the first study to disseminate scientific knowledge on the current situation, main clinical practice, and features of ACOS, asthma, and COPD conditions in Chinese patients. The insights will be helpful in designing optimal management strategies for ACOS and redefining the healthcare development programs.

Clinical significance of periodic detection of hepatitis B virus YVDD mutation by ultrasensitive real-time amplification refractory mutation system quantitative PCR during lamivudine treatment in patients with chronic hepatitis B.

Monitoring hepatitis B virus (HBV) mutants periodically during nucleoside analogue treatment is of great clinical significance, particularly in persistently HBV DNA-positive patients. However, few studies have investigated the dynamic changes of HBV YMDD (Tyr-Met-Asp-Asp) and YVDD (Tyr-Val-Asp-Asp) populations in chronic hepatitis B (CHB) patients whilst undergoing lamivudine (LMV) treatment. In this study, we sought to investigate the dynamic changes of HBV YMDD and YVDD variants by ultrasensitive real-time amplification refractory mutation system quantitative PCR (RT-ARMS-qPCR) and evaluate its significance for changes in the treatment of CHB patients. RT-ARMS-qPCR was established and evaluated with standard recombinant plasmids. Fifteen CHB patients receiving LMV (100 mg daily) were consecutively recruited and followed up for 60 weeks. Serum samples were obtained from each patient at baseline and every 12 weeks. The total HBV DNA, HBV YMDD DNA and YVDD DNA levels were measured using RT-ARMS-qPCR at all given time points after treatment. Routine liver biochemistry parameters, including aspartate aminotransferase and alanine aminotransferase, were also measured every 12 weeks. The linear range of the assay was between 1×10(12) and 1×10(5) copies ml(-1). The low detection limit was 1×10(4) copies ml(-1). After 60 weeks of LMV treatment, nine patients experienced virological breakthrough. The YVDD variant could be detected 12-48 weeks before virological breakthrough. The YVDD variant was detected as the predominant population (range 69.4-100 %) in patients by the time virological breakthrough appeared. We concluded that RT-ARMS-qPCR was sensitive for the detection and quantification of low levels of HBV mutation. Periodic detection of HBV YM(V)DD every 12 weeks during LMV treatment is helpful for therapeutic decision making.

Gingival health benefits of essential-oil and cetylpyridinium chloride mouthrinses: a 6-month randomized clinical study.

PURPOSE: This randomized, single center, examiner-blind, controlled, parallel-group, 6-month clinical study compared the antiplaque/antigingivitis potential of an essential oil (EO) versus a 0.07% cetylpyridinium chloride (CPC)-containing mouthrinse. A 5% hydroalcohol solution was included as a control group. METHODS: 354 healthy volunteers (18-71 years of age) were enrolled in this clinical trial; 338 subjects completed the study. At baseline, 1-, 3-, and 6-month visits, subjects received an oral examination, gingivitis (MGI), gingival bleeding (BI) and plaque assessments (PI). Following randomization, subjects received a prophylaxis and began brushing twice daily with the provided fluoride toothpaste and rinsing twice daily with 20 mL of the assigned mouthrinse for 30 seconds. RESULTS: All rinses were well tolerated by the subjects, with the exception of extrinsic tooth stain complaints in 13 subjects in the CPC group between the 3- and 6-month exams. Statistically significant reductions in gingivitis, bleeding and plaque were observed for both EO and CPC at all post-baseline time-points when compared to the negative control. At 6 months MGI and PI were reduced by 42.6% and 42.0% for EO and by 17.1% and 13.9% respectively, for CPC vs. control. When compared to CPC, EO was statistically significantly superior at all post-baseline time-points. EO showed increasing reductions in MGI of 10.5%, 20.3% and 30.7% as well as reductions in PI of 12.7%, 23.7% and 32.6% at 1, 3 and 6 months, respectively. When analyzing the number of healthy sites (MGI scores of 0 or 1), the beneficial effect of the EO-containing mouthrinse is 45.8% greater than using a CPC-containing mouthrinse and 59.8% greater than placebo.