Primary cardiac lymphoma: the management and outcome of a single-centre cohort of 22 patients.

BACKGROUND: The incidence of primary cardiac lymphoma (PCL) is increasing, but the optimal management approach remains unclear. We assessed the clinical characteristics of a single-centre cohort with the goal of determining the optimal management approach. The treatment outcomes and prognostic factors are reported. MATERIAL AND METHODS: All PCL patients were diagnosed via biopsy guided by whole-body imaging (positron emission tomography/computed tomography [PET/CT] and/or contrast-enhanced CT]. Curative therapy involved either surgery or prephase steroids followed by definitive immunochemotherapy, depending on the histological type. The primary outcomes were overall survival (OS) and progression-free survival (PFS); the secondary outcome was the treatment response. RESULTS: Twenty-two PCL patients (14 males, 8 females; age: 59.5 ± 14.7 years [mean ± S.D.]) were histologically confirmed to have diffuse large B-cell lymphoma (DLBCL; n = 17 [77.3%]), fibrin-associated DLBCL (FA-DLBCL) (n = 4 [18.2%]) and Burkitt lymphoma (n = 1 [4.5%]). Seven patients underwent cardiotomy (three for biopsy, four with curative intent). The median and longest follow-up periods were 16.3 and 180.0 months, respectively. The 16 patients who received curative therapy (complete response [CR], n = 15 [93.8%]; partial response [PR], n = 1 [6.2%]) showed better survival than those who did not (5-year OS: 83.0 ± 11.3% vs. 0%; hazard ratio [HR]: 0.025[95% confidence interval, CI: 0.003-0.187], p < 0.001); 5-year PFS: 78.7 ± 11.0% vs. 0%, HR= 0.010[0.001-0.093], p < 0.001). The left ventricular ejection fractions (LVEF) before and after definitive treatment was 63.6 ± 2.4% and 64.6 ± 4.5%, respectively (p = 0.275, power = 0.318). Extrapericardial lesions were associated with poorer survival (5-year OS: 40.0 ± 29.7% vs. 100%, p = 0.027; 5-year PFS:40.0 ± 21.9% vs. 100%, p = 0.010). CONCLUSIONS: Whole-body imaging is essential for diagnosis and prognosis. Curative therapy provided reasonable outcomes and survival; extrapericardial lesions were associated with a poorer treatment response.

Discrepancies between proxy estimates and patient reported, health related, quality of life: minding the gap between patient and clinician perceptions in heart failure.

PURPOSE: Health related quality of life (HRQoL) is rarely routinely measured in the clinical setting. In the absence of patient reported data, clinicians rely on proxy and informal estimates to support clinical decisions. This study compares clinician estimates (proxy) with patient reported HRQoL in patients with advanced heart failure and examines factors influencing discrepancies. METHODS: Seventy-five patients with heart failure, (22 females, 53 males) completed the EQ-5D-5L questionnaire. Thirty-nine clinicians (11 medical, 23 nursing, 5 allied health) completed the proxy version (V1) producing 194 dyads. Correlation was assessed using Spearman's rank tests, systematic bias was examined with Bland-Altman analyses. Inter-rater agreement at the domain level, was investigated using linear weighted Kappa statistics while factors influencing the IRG were explored using independent student t-tests, analysis of variance and regression. RESULTS: There was a moderate positive correlation between clinician HRQoL estimates and patient reported utility (r = 0.38; p < .0005). Mean clinician estimates were higher than patient reported utility (0.60 vs 0.54; p = 0.008), with significant underestimation of reported problems apparent in three of the five EQ-5D-5L domains. Patient sex (female), depressed mood and frailty were all associated with an increased inter-rater gap. CONCLUSION: Clinicians in this sample overestimated HRQoL. Factors affecting the inter-rater gap, including sex and depression, support formal HRQoL screening to enhance clinical conversations and decision making. The discrepancy also supports regulatory restriction on the use of expert opinion in the development of QALYs in health economic analysis.

EDTA-enhanced phytoremediation of heavy metals from sludge soil by Italian ryegrass (Lolium perenne L.).

Landscaping of sludge is a kind of recycling disposal, but the potential heavy metal risks limit its application. In this paper, the sludge soil was remediated by ryegrass, and the effect of ethylene diamine tetraacetic acid (EDTA) was studied through pot experiments. Italian ryegrass was planted in the sludge soil treated with six gradients concentrations of 0, 1, 2, 3, 4, 5 mmol kg-1 of EDTA, and the planting conditions were kept the same. After 45 days of planting, compared with the control group (without EDTA treated), the application of 1-5 mmol kg-1 EDTA decreased ryegrass biomass by 2-43%, reduced soil pH value by 0.21-0.34 unit, and reduced 4.1-9.7% capacity of exchange cation, but increased 1.4-8.6% soil organic matter. After growing ryegrass, the contents of heavy metals decreased by 10% for Cu, 15% for Zn, 6% for Ni, 14% for Cd and 44% for Pb; and after spraying EDTA decreased again by 33% for Cu, 31% for Zn, 56% for Ni, 24% for Cd, and 68% for Pb. In ryegrass, the uptake heavy metals were enhanced, and bio-concentration factor of Cu, Zn, Ni, Cd, and Pb of EDTA treated groups were 1.9, 1.6, 4.1, 2.7, and 4.8 times of the control group, respectively. However, EDTA only significantly increased transfer factor values of Cu and Zn, and made bio-extraction factor value of Cu greater than 1. The remediation factor values were used to comprehensive assess accumulation capacity of heavy metals by ryegrass under EDTA treating, and they ordered in Zn > Cu > Ni > Cd > Pb, and the best dose was 2 mmol kg-1 EDTA. Prediction models for bio-concentration factor were established by using stepwise multiple linear regression, explaining 94.9-99.3% of the corresponding elements with soil organic matter, EDTA dosage, and/or pH value (p < 0.005). This paper provided effective heavy metals remediation data for municipal sludge landscape and the prediction models.

Prevention of postpartum haemorrhage: cost consequences analysis of misoprostol in low-resource settings.

BACKGROUND: While inferior to oxytocin injection in both efficacy and safety, orally administered misoprostol has been included in the World Health Organization Model List of Essential Medicines for use in the prevention of postpartum haemorrhage (PPH) in low-resource settings. This study evaluates the costs and health outcomes of use of oral misoprostol to prevent PPH in settings where injectable uterotonics are not available. METHODS: A cost-consequences analysis was conducted from the international health system perspective, using data from a recent Cochrane systematic review and WHO's Mother-Baby Package Costing Spreadsheet in a hypothetical cohort of 1000 births in a mixed hospital (40% births)/community setting (60% births). Costs were estimated based on 2012 US dollars. RESULTS: Using oxytocin in the hospital setting and misoprostol in the community setting in a cohort of 1000 births, instead of oxytocin (hospital setting) and no treatment (community setting), 22 cases of PPH could be prevented. Six fewer women would require additional uterotonics and four fewer women a blood transfusion. An additional 130 women would experience shivering and an extra 42 women fever. Oxytocin/misoprostol was found to be cost saving (US$320) compared to oxytocin/no treatment. If misoprostol is used in both the hospital and community setting compared with no treatment (i.e. oxytocin not available in the hospital setting), 37 cases of PPH could be prevented; ten fewer women would require additional uterotonics; and six fewer women a blood transfusion. An additional 217 women would experience shivering and 70 fever. The cost savings would be US$533. Sensitivity analyses indicate that the results are sensitive to the incidence of PPH-related outcomes, drug costs and the proportion of hospital births. CONCLUSIONS: Our findings confirm that, even though misoprostol is not the optimum choice in the prevention of PPH, misoprostol could be an effective and cost-saving choice where oxytocin is not or cannot be used due to a lack of skilled birth attendants, inadequate transport and storage facilities or where a quality assured oxytocin product is not available. These benefits need to be weighed against the large number of additional side effects such as shivering and fever, which have been described as tolerable and of short duration.

Validation and comparison of EuroQoL-5 dimension (EQ-5D) and Short Form-6 dimension (SF-6D) among stable angina patients.

OBJECTIVES: Several preference-based health-related quality of life (HRQoL) instruments have been published and widely used in different populations. However no consensus has emerged regarding the most appropriate instrument in therapeutic area of stable angina. This study compared and validated the psychometric properties of two generic preference-based instruments, the EQ-5D and SF-6D, among Chinese stable angina patients. METHODS: Convergent validity of the EQ-5D and SF-6D was examined with eight a priori hypotheses from stable angina patients in conjunction with Seattle Angina Questionnaire (SAQ). Responsiveness was compared using the effect size (ES), relative efficiency (RE) and receiver operating characteristic (ROC) curves. Agreement between the EQ-5D and SF-6D was tested using intra-class correlation coefficient (ICC) and Bland-Altman plot. Factors affecting utility difference were explored with multiple linear regression analysis. RESULTS: In 411 patients (mean age 68.08 ± 11.35), mean utility scores (SD) were 0.78 (0.15) for the EQ-5D and 0.68 (0.12) for the SF-6D. Validity was demonstrated by the moderate to strong correlation coefficients (Range: 0.368-0.594, P< 0.001) for five of the eight hypotheses in both the EQ-5D and SF-6D. There were no serious floor effects for the EQ-5D and SF-6D, but ceiling effects for the EQ-5D were large. The areas under ROC of them all exceeded 0.5 (0.660-0.814, P< 0.001). The SF-6D showed a better discriminative capacity (ES: 0.573 to 1.179) between groups with different stable-angina-specific health status than the EQ-5D (ES: 0.426 to 1.126). RE suggested that the SF-6D (RE: 44.8 to 177.8%) was more efficient than the EQ-5D except for physical function. Poor agreement between them was observed with ICC (0.448, P< 0.001) and Bland-Altman plot analysis. Multiple liner regression showed that clinical variables significantly (P< 0.05) influenced differences in utility scores between the EQ-5D and SF-6D. CONCLUSIONS: Both EQ-5D and SF-6D are valid and sensitive preference-based HRQoL instruments in Chinese stable angina patients. The SF-6D may be a more effective tool with lower ceiling effect and greater sensitivity. Further study is needed to compare other properties, such as reliability and longitudinal response.

Real-world treatment patterns and outcomes for patients with CLL using the Australian pharmaceutical benefits scheme (PBS) dataset.

This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies.

Clinical evaluation of droplet digital pcr for suspected ascites infection in patients with liver cirrhosis.

BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.

Time-dependent movement and distribution of chlorothalonil and chlorpyrifos in tomatoes.

Determining the distribution of pesticides in fruits is essential to eliminate pesticide residues during food processing. In this study, the dynamic distribution of two pesticides, chlorothalonil (CHT) and chlorpyrifos (CHP), were determined in different tomato parts following immersion in pesticide solutions. The concentrations of CHT and CHP in tomato followed an order of cuticle>plasma>pulp. However, the plasma initially accumulated the highest pesticide concentration. And the ratio of CHT concentration to that of CHP in plasma was about 2.1:1, similar to the ratio in solution, which suggested carpopodium as the entry site for the pesticides tested. The ratio in the cuticle was 0.02:1-0.06:1. This was consistent with the ratio of Kow for the two pesticides, manifesting the direct pesticide transfer from solution to cuticle. Following pesticide injection into tomato, the degradation of CHT over 96h was described by a first-order decay equation, Ctomato(t)CHT=C0×e(-0.0239t). The CHP concentration in tomato remained nearly constant with little degradation detected. Deducting the amount of degradation and migration, volatilization appeared to contribute the most amount of migration of CHT and CHP in tomato.

Favorable prognosis of female patients with nasopharyngeal carcinoma.

The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this phenomenon. To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.

[Effect of coicis semen oil on renal interstitial fibrosis in rats with unilateral urethral obstruction].

OBJECTIVE: To study the effect and mechanism of Coicis Semen oil (Kanglaite injection, KLT) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHOD: Fifty-four male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KLT group. Renal interstitial fibrosis model was established in rats by UUO. After administration of KLT (15 mL x kg(-1) x d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1) were measured by immunohistochemistry staining sections. The protein expression of p-Smad2 and Smad7 were detected by Western blot respectively. RESULT: The degree of tubular damage in KLT group was much lower than that in UUO group (P < 0.05). The expression of alpha-SMA and TGF-beta1 was decreased in both UUO group and KLT group, while it was significantly lower in KLT group at every time point. The protein expression of p-Smad2 was obviously decreased while the protein expressions of Smad7 was obviously increased in KLT group, compared with the UUO group (P < 0.05). CONCLUSION: Coicis Semen oil could attenuate the tubulo-interstitial fibrosis, probable by intervening the TGF-beta/Smads signal transduction pathway of UUO rats.

Patient Access to Orphan Drugs Covered by Medical Insurance in China: Real-World Evidence From Patient Survey.

BACKGROUND: After the inclusion of more high-cost orphan drugs in China's National Reimbursement Drugs List, this study investigated issues relating to patient access to the 7 medicines for 4 rare diseases after listing. METHODS: This study collected data from a national survey conducted in China. Three aspects associated with the accessibility of medicines, namely, approachability, availability, and affordability, were analyzed using descriptive statistics. In addition, multilevel logistic regression models were used to investigate the associations between patient characteristics and the accessibility of surveyed orphan drugs. RESULTS: Of the 999 completed responses included in the study, 15% of the patients (n = 150) did not use the medicines because of non-medicine-related issues. Among the 849 patients using the surveyed medications, 64.4% (n = 547) encountered the problem of unavailability, whereas 51.2% (n = 435) reported affordability as an issue, and 49.6% (n = 320) had health expenditure beyond the catastrophic threshold. The data also indicated that Commercial Medical Insurance helped patients to relieve the cost burden on orphan drugs, but the payout of Commercial Medical Insurance failed to influence patients' decisions to continue the treatments. CONCLUSION: Accessibility of orphan drugs has improved in China after their inclusion in the National Reimbursement Drugs List. Nevertheless, the availability and affordability of medicines remained the barriers for patients to access the desired treatments. It is recommended that further policy refinement in conjunction with the collaboration among healthcare stakeholders is required to deliver better care for patients with rare disease.

Clinical Evaluation of Metagenomic Next-Generation Sequencing Method for the Diagnosis of Suspected Ascitic Infection in Patients with Liver Cirrhosis in a Clinical Laboratory.

Metagenomic next-generation sequencing (mNGS), mostly carried out in independent clinical laboratories, has been increasingly applied in clinical pathogen diagnosis. We aimed to explore the feasibility of mNGS in clinical laboratories and analyze its potential in the diagnosis of infectious ascites. Two reference panels composed of 12 strains commonly appearing in peritonitis were constructed to evaluate the performance metrics based on in-house mNGS protocols. The mNGS clinical detection value was analyzed in 211 ascitic samples and compared with culture and composite standards. Finally, eight patients with cirrhosis were prospectively enrolled to verify the clinical value of mNGS in peritoneal infection diagnosis. The mNGS analytical performance showed that the assay had great linearity, specificity, stability, interference, and limits of detection of 33 to 828 CFU/mL. The sensitivity and specificity of mNGS for bacterial or fungal detection using culture standards were 84.2% and 82.0%, respectively. After adjustment using digital PCR and clinical judgment, the sensitivity and specificity increased to 87.2% and 90.1%, respectively. Compared with culture, mNGS detected a broad range of pathogens and more polymicrobial infections (49% versus 9%, P < 0.05). The pathogen results were obtained within 24 h using mNGS in eight prospective cases, which effectively guided antibiotics therapy. mNGS testing in clinical laboratories affiliated with a hospital has certain advantages. It has unique superiority in pathogens detection, particularly in patients with polymicrobial infections. However, considering spectrum characteristics and test cost, pertinent pathogen panels should be developed in clinical practice. IMPORTANCE This study established and evaluated a complete metagenomics next-generation sequencing assay to improve the diagnosis of suspected ascitic infection in a clinical laboratory affiliated with a hospital. The assay is superior to traditional culture testing and will aid in the early and accurate identification of pathogens, particularly in patients with polymicrobial infections. This assay is also essential for precision therapy and can reduce the incidence of drug resistance stemming from irrational use of antibiotics.

Clinical outcomes of newly diagnosed primary central nervous system lymphoma treated with zanubrutinib-based combination therapy.

BACKGROUND: High-dose methotrexate (HD-MTX) combined with other chemotherapeutic agents is an effective treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL); however, some patients have adverse reactions. AIM: To retrospectively evaluate disease outcomes and mutational profiles in newly diagnosed PCNSL patients treated with a zanubrutinib/HD-MTX combination regimen. METHODS: Nineteen newly diagnosed PCNSL patients were treated with zanubrutinib/HD-MTX until disease progression, intolerable toxicities, or physician/patient-directed withdrawal. Safety and efficacy were assessed per the CTCAE v5.0 and RECIST v1.1 criteria, respectively. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were progression-free survival, overall survival (OS), and safety. RESULTS: The median follow-up duration was 14.7 mo (range, 3.9-30 mo). The ORR for all patients was 84.2%, and 2-year progression-free- and OS rates were 75.6% and 94.1%, respectively. All patients completed the induction phase, and nine patients underwent autologous stem cell transplantation as consolidation therapy, resulting in an ORR of 88.9%. Ten patients received zanubrutinib as maintenance therapy and achieved an ORR of 80%. All patients showed an acceptable safety profile. The sequencing results for cerebrospinal fluid (CSF) and tumor tissue showed that PIM1 mutations were the most frequent genetic alterations. Circulating tumor DNA was correlated with disease relapse and response. CONCLUSION: Our empirical observations demonstrated that the combination of zanubrutinib with HD-MTX yielded a marked clinical response and tolerability among newly diagnosed PCNSL patients. Non-invasive CSF liquid biopsy profiling may be feasible for evaluating treatment response and tumor burden.

Cost-utility analysis of liraglutide versus glimepiride as add-on to metformin in type 2 diabetes patients in China.

OBJECTIVES: The aim of this study was to evaluate the long-term cost-utility of liraglutide versus glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM), based on the results of clinical trial conducted in Asian population. METHODS: The validated UKPDS Outcomes Model was used to project life expectancy, quality adjusted life-years (QALYs), incidence of diabetes-related complication and cost of complications in patients receiving those regimens. Baseline cohort characteristics and treatment effects were derived from an Asian study. China-specific complication costs and utility score were taken from local studies. Patients' outcomes were modeled for 30 years and incremental cost-effectiveness ratios were calculated for liraglutide compared with glimepiride from the healthcare system perspective. Both future costs and clinical benefits were discounted at 3 percent. Sensitivity analyses were performed. RESULTS: Over a period of 30 years, compared with glimepiride, liraglutide 1.8 mg was associated with improvements in life expectancy (0.1 year) and quality adjusted life-year (0.168 QALY), and a reduced incidence of diabetes-related complications leading to an incremental cost-effectiveness ratio per QALY gained versus glimepiride of CNY 25,6871 (DEC 2010, 1 USD = 6.6227 CNY). CONCLUSIONS: Long-term projections indicated that liraglutide was associated with increased life expectancy, QALYs, and reduced complication incidences comparing with glimepiride. When the UK cost of liraglutide was discounted by 38 percent, liraglutide would be a cost-effective option in China from the healthcare system perspective using the 3X GDP/capita per QALY as the WTP threshold.

Altered transfer of heavy metals from soil to Chinese cabbage with film mulching.

The influence of film mulching on the migration of metals from soil to cabbage was investigated. Following a 50-day growth in field plots mulched or unmulched, root-zone soils and Chinese cabbage (Brassica chinensis L.) were sampled for metal analysis. Mulching slightly decreased the soil mobile (acid-extractable) Cd, but increased its transfer from root to the cabbage parts. As an essential element, Cu was readily transferred to the cabbage parts. While mulching decreased the soil mobile Zn, reduced soil pH resulted in its enhanced soil-to-root migration. This, however, did not increase the transfer of Zn within cabbage. Although mulching increased the soil mobile Pb by 200%, an increase in Pb in cabbage leaves but a decrease in stem result presumably from the enhanced foliar uptake of atmospheric Pb. This study suggests that mulching may promote the accumulation of toxic metals such as Cd and Pb in cabbage and therefore increase crop risks to human health.

Mitoxantrone exerts both cytotoxic and immunoregulatory effects on activated microglial cells.

Mitoxantrone (MX) is the most common immunosuppressive drug used in patients with rapidly worsening multiple sclerosis (MS), whose disease is not controlled by ß-interferon or glatiramer acetate. Although MX suppresses antigen-presenting cell (APC) and T-cell function in the periphery, its mechanism of action in the central nervous system (CNS) is not known. Given that MX can cross the disrupted blood-brain barrier, such as in MS patients, we in the present study have tested our hypothesis that MX in the CNS exerts cytotoxic and immunomodulatory effects on microglia, the major CNS-resident APCs that play a crucial role in MS pathogenesis. The cytotoxic effect of MX on microglial cells was determined by MTT and flow cytometry test, whereas the regulatory function was tested with enzyme-linked immunosorbent assay (ELISA) method. Indeed, we have found that MX induced microglial cell death in a dose-dependent manner, and the cell death was mainly from late apoptosis and necrosis. Further, MX induced significantly increased levels of interleukin (IL)-10 production of microglia, whereas IL-23p19 production/expression was significantly suppressed. Thus, our study for the first time demonstrates the immunosuppressive/regulatory effect of MX on microglia, which represents an important mechanism underlying the therapeutic effect of this drug on MS patients.

Psychometric Evaluation of the Mandarin HeartQoL Health-Related Quality of Life Questionnaire Among Patients With Ischemic Heart Disease in China.

OBJECTIVES: This study evaluated the psychometric properties of the Mandarin version of the HeartQoL questionnaire, a core ischemic heart disease (IHD) health-related quality of life (HRQL) instrument, in patients with angina, myocardial infarction (MI), and ischemic heart failure (IHF). METHODS: The English version of HeartQoL was translated into Mandarin. A cross-sectional study was then conducted in mainland China using the Mandarin HeartQoL, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale. Factor analysis was used to establish the HeartQoL structure and internal consistency reliability and construct validity were assessed. RESULTS: Patients with IHD (n = 412; angina = 112, MI = 151, and IHF = 149) were enrolled. Significantly higher HeartQoL HRQL scores were reported by patients with either angina or MI than by patients with IHF. The 2-factor structure was confirmed by Mokken scale analysis in the total group with strong H coefficients on the global scale (0.64) and both the physical (0.70) and emotional (0.80) subscales. Internal consistency reliability was strong with Cronbach's α ranging from 0.90 to 0.95. Convergent validity was confirmed with strong correlations between similar physical and mental HeartQoL and Short Form-12 Health Survey subscales ranging from 0.77 to 0.82 with divergent validity confirmed with significantly lower correlations between dissimilar constructs. Discriminative validity was confirmed for 72% of the a priori sociodemographic and clinical hypotheses. CONCLUSIONS: The Mandarin version of the HeartQoL HRQL questionnaire demonstrates acceptable internal consistency reliability and convergent, divergent, and discriminative validity in patients with IHD and in each diagnostic subgroup. The data support the use of the HeartQoL to assess and compare HRQL in Mandarin-speaking patients with IHD.

Willingness to pay per quality-adjusted life year: is one threshold enough for decision-making?: results from a study in patients with chronic prostatitis.

OBJECTIVE: To estimate the willingness to pay (WTP) per quality-adjusted life year (QALY) ratio with the stated preference data and compare the results obtained between chronic prostatitis (CP) patients and general population (GP). METHODS: WTP per QALY was calculated with the subjects' own health-related utility and the WTP value. Two widely used preference-based health-related quality of life instruments, EuroQol (EQ-5D) and Short Form 6D (SF-6D), were used to elicit utility for participants' own health. The monthly WTP values for moving from participants' current health to a perfect health were elicited using closed-ended iterative bidding contingent valuation method. RESULTS: A total of 268 CP patients and 364 participants from GP completed the questionnaire. We obtained 4 WTP/QALY ratios ranging from $4700 to $7400, which is close to the lower bound of local gross domestic product per capita, a threshold proposed by World Health Organization. Nevertheless, these values were lower than other proposed thresholds and published empirical researches on diseases with mortality risk. Furthermore, the WTP/QALY ratios from the GP were significantly lower than those from the CP patients, and different determinants were associated with the within group variation identified by multiple linear regression. CONCLUSIONS: Preference elicitation methods are acceptable and feasible in the socio-cultural context of an Asian environment and the calculation of WTP/QALY ratio produced meaningful answers. The necessity of considering the QALY type or disease-specific QALY in estimating WTP/QALY ratio was highlighted and 1 to 3 times of gross domestic product/capita recommended by World Health Organization could potentially serve as a benchmark for threshold in this Asian context.

Direct qualitative and quantitative determination methodology for massive screening of DON in wheat flour based on multi-molecular infrared spectroscopy (MM-IR) with 2T-2DCOS.

Deoxynivalenol (DON) contamination in wheat flour induces a number of adverse health effects to consumers and livestock, even at very low concentrations. Direct detection methods for massive screening of DON in wheat flour is still lacking. A new methodology integrating multi-molecular infrared spectroscopy (MM-IR) with two-trace two-dimensional correlation spectroscopy (2T-2DCOS) was developed for in-situ qualitative and quantitative determination of DON in wheat flour as a whole. Typical spectral variation of wheat flour samples with diverse concentration of DON were stepwise characterized by MM-IR and tiny spectral profile differences resulting from concentration variation of DON were visually disclosed by 2T-2DCOS. Based on the obtained key spectral features of DON, 180 of wheat flour samples with DON higher and lower than 1.00 mg/kg were undoubtedly classified by Principal Component Analysis (PCA) and Support Vector Machines (SVM) with an accuracy rate up to 100% (for Second derivative spectra consisted of selected bands, SD-SS). Furthermore, a robust quantitative prediction model was established based on partial least squares (PLS) of SD-SS (Rc: 0.998, RMSEC: 0.135; Rp: 0.968, RMSEP: 0.421), and its excellent predictive capacity of model was validated by both residual prediction deviation (RPD) value of 3.2 and t-test. It was demonstrated that the developed methodology was applicable for screening and quantitative detection of DON in wheat flour based on the novel correlation analysis methods (SD-2DCOS-IR and 2T-2DCOS-IR) with chemometrics tools, which could be utilized both at laboratory and industrial level for quality control purposes of a large wheat flour sample set.

[Identify the Nitrate Sources in Different Land Use Areas Based on Multiple Isotopes].

Different land uses have different impacts on the water quality of the region. Multiple isotopes (δD-H2O, δ18O-H2O, δ15N-NO3-, and δ18O-NO3-) and the SIAR (stable isotope analysis in R) model were applied to identify the nitrate sources and estimate the proportional contributions of multiple nitrate sources in a river in a typical urban area (the Grand Canal, Hangzhou) and a river in a typical forest and agricultural area (Yuying Riveri). The results indicated that there were different degrees of nitrogen pollution in the Grand Canal and Yuying River; NO3--N and NH4+-N are the predominant forms of nitrogen in the Grand Canal, and the primary form of nitrogen in Yuying River was NO3--N. There was an obvious linear relationship between the hydrogen and oxygen isotopes (R2=0.78). The δD-H2O and δ18O-H2O values for the Grand Canal and Yuying River were distributed along the local meteoric waterline, indicating that precipitation served as the primary water source in these rivers. All of the δ18O-NO3- values of the Grand Canal and Yuying River were lower than 15 ‰. It was revealed that nitrification, rather than denitrification, was the primary N cycling process in the two rivers. The δ15N-NO3-/δ18O-NO3- ratios of some of the samples from the Grand Canal ranged from 1.3 to 2.1, accompanied by low concentrations of DO and NO2-, indicating that denitrification existed in some sections of the Grand Canal. The δ15N-NO3- values of the samples from the Grand Canal (average:6.1‰) were higher than those from the Yuying River (average:2.3‰). The NO3- source contributions differed significantly between the Grand Canal and Yuying River. The contributions of NO3- sources in the Grand Canal were sewage/manure (37.0%) > soil nitrogen (35.7%) > chemical fertilizer (19.1%) > precipitation (8.2%), and those in the Yuying River were chemical fertilizer (46.1%) > soil nitrogen (22.8%) > precipitation (17.3%) > sewage/manure (13.8%). The contribution of the sewage/manure was substantially increased in the Grand Canal in the urban area with stronger human activities primarily due to the sporadic discharge of domestic sewage and urban runoff. Chemical fertilizer is the main NO3- source in the Yuying River near the forest and agricultural area, suggesting that the nitrogen pollution caused by agricultural non-point sources was extremely serious. The contribution of precipitation decreased in the areas of substantial human activities. The isotopic fractionation produced by denitrification was affected by the contributions of the NO3- sources, which were calculated by SIAR model. Sewage/manure and chemical fertilizer produced significant impacts, followed by soil nitrogen and precipitation.