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Objectives: The poor detection rate of multidrug-resistant tuberculosis (MDR-TB) highlights the urgent need to explore new case finding model to improve the detection of MDR-TB in China. The aim of this study was to evaluate the feasibility of a new model that combines molecular diagnostics and sputum transportation for early detection of patients with MDR-TB in Zhejiang.Methods: From May 2014 to January 2015, TB suspects were continuously enrolled at six county-level designated TB hospitals in Zhejiang. Each patient gave three sputum samples, which were submitted to laboratory for smear microscopy, solid culture and GeneXpert. The specimens from rifampin (RIF)-resistant cases detected by GeneXpert, and positive cultures were transported from county-level to prefecture-level laboratories for line probe analysis (LPA) and drug susceptibility testing (DST). The performance and interval of MDR-TB detection of the new model were compared with those of conventional model.Results: A total of 3151 sputum specimens were collected from TB suspects. The sensitivity of GeneXpert for detecting culture-positive cases was 92.7% (405/437), and its specificity was 91.3% (2428/2659). Of 16 RIF-resistant cases detected by DST, GeneXpert could correctly identify 15 cases, yielding a sensitivity of 93.8% (15/16). The specificity of GeneXpert for detecting RIF susceptibility was 100.0% (383/383). The average interval to diagnosis of the conventional DST model was 56.5 days, ranging from 43 to 71 days, which was significantly longer than that of GeneXpert plus LPA (22.2 days, P < 0.01).Conclusion: Our data demonstrate that the combination of improved molecular TB tests and sputum transportation could significantly shorten the time required for detection of MDR-TB, which will bring benefits for preventing an epidemic of MDR-TB in this high-prevalence setting. [ABSTRACT FROM AUTHOR]

Implementing joint distribution between express service providers is important in order to achieve operational efficiency and reduce operational cost. Joint distribution centers (JDCs) are an important part of the modern urban logistics system for online shopping, and selecting the location for a JDC has become a key problem for stakeholders considering sustainability. In this paper, we present a new hybrid fuzzy multiple-criteria decision-making method for selecting the location of a JDC considering sustainability. First, we identify the evaluation criteria for location selection integrating the economic, environmental, and social dimensions of sustainability. Secondly, a fuzzy set is used to translate linguistic preferences into triangular fuzzy numbers. Subjective criteria weights are calculated by combining the decision makers’ superiority linguistic ratings with a fuzzy AHP method. Objective criteria weights are determined by combining superiority linguistic ratings with a fuzzy-entropy method. Then, improved fuzzy TOPSIS is achieved by using weighted criterion distances to rank these alternatives. This permits a more stable ranking order to be obtained compared to traditional fuzzy TOPSIS which uses Euclidean distance. Finally, an empirical location selection and sensitivity analysis study is conducted to illustrate the effectiveness and robustness of the proposed method. This new method allows the location of a JDC to be selected considering sustainability, and will contribute to promoting the sustainable development of China’s express industry and, to some extent, the sustainability and harmony of city development. [ABSTRACT FROM AUTHOR]

Sediment accumulation and budget in the continental margins provides abundant information of source-sink processes from the land to the sea, including weathering, human activities and sedimentary environment. Here we show the distribution of mud areas, modern sedimentation rates and sediment budget in the Bohai Sea, Yellow Sea and East China Sea. Using grain size data of > 18,000 surface sediment samples and 210 Pb data from 413 sites, we identify five areas with sediments mainly composed of fine-grained fractions (mean grain size > 6 φ) and find a relatively high sedimentation rates of > 1.5 mm/yr in the mud areas. Near the Yellow and Yangtze River deltas sedimentation reaches > 95.0 mm/yr. Approximately 1185.4 × 10 6 tons of fine-grained sediment accumulate annually in the mud areas of the east China seas. Atmospheric deposition contributes < 2% (18.37 × 10 6 tons/yr), while the riverine sediment inputs account for > 75% (917 × 10 6 tons/yr). The remainder comes from all other sources including coastal erosion and resuspension of bottom sediments. In addition, ~ 45% of the fluvial sediment supply deposits on the subaerial delta, ~ 40–50% is trapped on the subaqueous delta and shelf, and the remainder < 5% escapes the shelf edge. The results will be a strong foundation for understanding of the transport, deposit and preservation of sediment and other relevant material (e.g. carbon and nutrient etc.) of terrestrial materials in the sea. [ABSTRACT FROM AUTHOR]

To explore the effects of traditional Chinese medicine constitution (TCMC) on transformation of good health status to suboptimal health status (SHS), we conducted a nested case-control study among college students in China. During the 18-month mean follow-up time, 543 cases of SHS (42.7%) occurred in 1273 healthy students. There was a significant (P=0.000) and marked reduction in SHMS V1.0 total score in the case group at the 18-month follow-up (69.32 ± 5.45) compared with baseline (78.60 ± 4.70), but there was no significant change in the control group. Conditional logistic regression analysis showed that respondents reporting Yin-deficiency and Qi-deficiency were, respectively, 2.247 and 2.198 times more likely to develop SHS, while tendency to Yin-deficiency and tendency to Damp-heat were, respectively, 1.642 and 1.506 times more likely to develop SHS. However, the Balanced Constitution was a significant protective factor (OR 0.649; P<0.05). Altogether, these findings demonstrate that Yin-deficiency, Qi-deficiency, tendency to Yin-deficiency, and tendency to Damp-heat appeared to induce a change in health status to SHS, while the Balanced Constitution seemed to restrain this change. We conclude that regulating the unbalanced TCMC (such as Yin-deficiency and Qi-deficiency) may prevent a healthy status developing into SHS or lead to the regression of SHS. [ABSTRACT FROM AUTHOR]

• Combination of nifuroxazide and CpG ODN inhibited the HCC growth in mice. • Combination treatment prompted T cell anti-tumor immune response in mice. • Combination treatment increased M1 macrophage infiltration in tumor-tissues. Hepatocellular carcinoma (HCC) is a common malignant tumour in China that remains a major challenge to the medical community, and effective treatment is urgently needed. Due to complex tumorigenesis, monotherapy shows poor therapeutic effects, and combined treatment becomes a necessary option. YW002, a CpG ODN-containing sequence, has been proven to enhance antitumor effects in tumour-bearing mouse models. Moreover, as a broad-spectrum antimicrobial drug, nifuroxazide exhibited an anti-HCC effect through activation of p-Stat3. Here, we tested the effect of nifuroxazide on HCC in vitro and then explored the therapeutic effect of combined nifuroxazide and CpG ODN on HCC in vivo. Nifuroxazide inhibited proliferation, induced apoptosis and suppressed migration and invasion in HepG2 cells in vitro. The combination therapy using nifuroxazide and CpG ODN significantly suppressed the growth of tumours in tumour-bearing mice with few side effects and achieved better therapeutic effects on HCC than monotherapy. Moreover, combined nifuroxazide and CpG ODN therapy significantly induced apoptosis, enhanced the infiltration of CD4+ and CD8+ T lymphocytes and macrophages in tumour tissue, and increased the ratio of CD4+ and CD8+ T lymphocytes in the spleens of tumour-bearing mice. The introduction of this combination therapy combining nifuroxazide and CpG ODN provided a new strategy for HCC treatment. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) and HIV are two worldwide public health concerns. Co-infection of these two diseases has been considered to be a major obstacle for the global efforts in reaching the goals for the prevention of HIV and TB. Method: A comprehensive cross-sectional study was conducted to recruit TB patients in three provinces (Guangxi, Henan and Sichuan) of China between April 1 and September 30, 2010. Results: A total of 1,032 consenting TB patients attended this survey during the study period. Among the participants, 3.30% were HIV positive; about one quarter had opportunistic infections. Nearly half of the participants were 50 years or older, the majority were male and about one third were from minority ethnic groups. After adjusting for site, gender and areas of residence (using the partial/selective Model 1), former commercial plasma donors (adjusted OR [aOR] = 33.71) and injecting drug users(aOR = 15.86) were found to have significantly higher risk of being HIV-positivity. In addition, having extramarital sexual relationship (aOR = 307.16), being engaged in commercial sex (aOR = 252.37), suffering from opportunistic infections in the past six months (aOR = 2.79), losing 10% or more of the body weight in the past six months (aOR = 5.90) and having abnormal chest X-ray findings (aOR = 20.40) were all significantly associated with HIV seropositivity (each p<0.05). Conclusions: HIV prevalence among TB patients was high in the study areas of China. To control the dual epidemic, intervention strategies targeting socio-demographic and behavioral factors associated with higher risk of TB-HIV co-infection are urgently called for. [ABSTRACT FROM AUTHOR]

Background Maintenance therapy for extensive stage small cell lung cancer ( ES-SCLC) is still under debate. Many new agents fail during the maintenance course. As an active agent for SCLC, oral etoposide is worth being re-evaluated. Methods This phase II study was performed to evaluate the toxicity/efficacy of the maintenance of patients with oral etoposide with ES-SCLC responding (complete remission [ CR] + partial remission [ PR]) to the induction of four cycles of etoposide plus cisplatin ( EP) chemotherapy. Maintenance therapy with oral etoposide (50 mg/m2, day 1-14, repeated every 21 days until disease progression or unacceptable toxicity occurs) was administered. The primary endpoints were grade 3 and 4 toxicities and progression free survival ( PFS). Results Fifty-four patients with ES-SCLC received standard EP regimens as induction therapy; 31 responding patients were administered oral etoposide as the maintenance treatment. The most common hematological and non-hematological toxicity of the maintenance course was neutropenia and fatigue, respectively. Median PFS was nine months (95% confidence interval ( CI): 8.33∼9.67 months), median overall survival ( OS) was 14 months (95% CI: 11.58∼16.42 months). Significantly better PFS and OS were seen in patients responding to the induction EP chemotherapy. Conclusions Oral etoposide maintenance is safe and effective for patients with ES-SCLC who responded to the induction of EP chemotherapy. Significant survival benefit was revealed in patients completely responding to an EP regimen. Further randomized control study is warranted. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and hepatitis C virus (HCV)-HCC are the main indications for liver transplantation. We compared differences in survival outcomes between these two conditions. Methods and Findings: The China Liver Transplant Registry (CLTR) contains data collated from all transplants performed in 86 liver transplantation centers across China. We analyzed CLTR data from January 1999 to December 2010. In all, 7,658 patients (7,162 with HBV-HCC and 496 with HCV-HCC) were included in this study. Clinical characteristics were compared between the HBV-HCC and HCV-HCC groups; Kaplan–Meier analysis was used to calculate the overall, tumor-free and hepatitis-free survival rates. The 1-year, 3-year and 5-year overall survival was significantly higher in HBV-HCC recipients than in HCV-HCC recipients (76.65%, 56.61% and 49.10% vs. 64.59%, 42.78% and 39.20%, respectively; P<0.001). The corresponding tumor-free survival rates (63.55%, 47.37%, 40.99% vs. 56.84%, 38.04%, 35.66%, respectively) and hepatitis-free survival rates (75.49%, 54.84%, 47.34% vs. 63.87%, 42.15%, 39.33%, respectively) were both superior in HBV-HCC recipients (both P<0.001). Multivariate analyses identified hepatitis, preoperative alpha-fetoprotein (AFP) level, size of largest tumor, number of tumor nodules, TNM stage, vascular invasion and preoperative model for end-stage liver disease (MELD) score as independent predictors of overall, tumor-free and hepatitis-free survival. Conclusions: Survival outcomes after liver transplantation were significantly better in HBV-HCC patients than in HCV-HCC patients. This finding may be used to guide donor liver allocation in transplantation programs. [ABSTRACT FROM AUTHOR]

Abstract: Beta-Hemolytic group G streptococci cause a considerable invasive disease burden and sometimes disease outbreaks. Little is known about the critical epidemiologic parameter of genetic relatedness between isolates. We determined the emm types of 65 Streptococcus dysgalactiae subsp. equisimilis isolates. We formulated multilocus sequence typing (MLST) primers with 6 of the 7 loci corresponding to the Streptococcus pyogenes MLST scheme. We performed MLST with 69 S. dysgalactiae subsp. equisimilis isolates to represent each emm type identified. These strains were further analyzed by pulsed-field gel electrophoresis (PFGE) typing. Sixteen emm types were observed. Eighteen unique combinations of allelic profiles (sequence types [STs]) were obtained with 12 profiles each accounting for multiple isolates. Forty-one MLST STs were observed. Analysis of the PFGE patterns generated revealed 10 clones. Over 80% of the isolates were distributed in 3 large clones. Isolates within 16 redundantly represented S. dysgalactiae subsp. equisimilis emm types shared identical or nearly identical STs and subtypes of PFGE, demonstrating concordance between the emm type and genetic relatedness. It is conceivable that some particular characteristics in the genomes of these strains are responsible for their predominance in different regions. [Copyright &y& Elsevier]

[Display omitted] • A suitable 1H qNMR-based technique was used to quantify total macamide in five maca. • This method show potential for the quality control of maca. • A new macamide represents the first example of macamides with azelaxyl fraction. Macamides are considered bioactive markers of maca, and they have been used as food and medicine for centuries. In the present study, a 1H qNMR method was developed, and the analyses of the specificity, linearity, sensitivity, accuracy, and precision further indicate the validity of this method. Furthermore, the 1H qNMR method was applied for the quantification of total macamides in five naturally air-dried maca samples with different origins and colors. The results showed that the content of total macamides was correlated with the origins and colors: China purple maca (1845.75 ± 3.45 μg g−1) > China yellow maca (1090.20 ± 2.07 μg g−1) > Peru yellow maca (393.30 ± 2.42 μg g−1) > China and Peru black maca (each 269.10 ± 1.03 μg g−1). In addition, a new macamide, N -benzyl-(9-carboxymethyl)-octanamide (2), which is the first example of a macamide with an azelaxyl motif, was identified from Chinese purple maca. Our research not only provides a valid method to determine the content of total macamides in different maca samples but also offers a reference for quality control of maca. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Recently, the (GGC) n repeat expansion in the NOTCH2NLC gene has been identified to be associated with neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of dementia-dominant NIID with neurodegenerative dementia, we therefore hypothesized that the NOTCH2NLC repeat expansion might also contribute to these diseases. In the present study, repeat primed polymerase chain reaction (RP-PCR) and GC-rich PCR were conducted to detect the repeats of NOTCH2NLC in a cohort of 1004 patients with neurodegenerative dementias from mainland China. As a result, 4 sporadic patients were found to carry the NOTCH2NLC repeats expansion, totally accounting for 0.4% of all dementia individuals, and the accurate repeated sizes were 110, 133,120 and 76 respectively. Of 4 mutation carriers, three and one were clinically diagnosed Alzheimer's disease (AD) and frontotemporal dementia (FTD) respectively. In addition, 3 out of them revealed leukoencephalopathy in T2-Flair imaging. This study revealed that although rare, the NOTCH2NLC repeat expansions may be associated with AD or FTD-like phenotype as well as leukoencephalopathy. • The GGC repeat expansions in the NOTCH2NLC gene were identified in patients with.AD and FTD. • Of cases with repeats expansions, three showed leukoencephalopathy in T2-Flair imaging. • The repeat expansions in NOTCH2NLC may be associated with AD or FTD-like phenotypes as well as leukoencephalopathy. [ABSTRACT FROM AUTHOR]

Background: Early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is associated with poor surgical outcomes. This study aims to construct a preoperative model to predict individual risk of post-LT HCC recurrence.Methods: Data of 748 adult patients who underwent deceased donor LT for HCC between January 2015, and February 2019 were collected retrospectively from the China Liver Transplant Registry database and randomly divided into training (n = 486) and validation(n = 262) cohorts. A multivariate analysis was performed and the five-eight model was developed.Results: A total of 748 patients were included in the study; of them, 96% had hepatitis B virus (HBV) and 84% had cirrhosis. Pre-LT serum alpha-fetoprotein (AFP), tumor number and largest tumor diameter were incorporated to construct the 5-8 model which can stratify patients accurately according to their risk of recurrence into three prognostic subgroups; low-(0-5 points), medium-(6-8 points) and high-risk (> 8 points) with 2-year post-LT recurrence rate of (5,20 and 51%,p <  0.001) respectively. The 5-8 model was better than Milan, Hangzhou, and AFP-model for prediction of HCC early recurrence. These findings were confirmed by the results of the validation cohort.Conclusions: The 5-8 model is a simple validated and accurate tool for preoperative stratification of early recurrence of HCC after LT. [ABSTRACT FROM AUTHOR]

The major obstacles to strengthening the primary care system in China are shortages of finance and workforce, especially in rural and low-income areas. To address these barriers, in 2009, Pengshui County (Chongqing, China), implemented a reform on its primary care delivery system, with a focus on horizontal integration and financing mechanisms. We aimed to analyse the horizontal integrated-care model and evaluate the effect of the reform in the past 10 years. We analysed the reform to the primary care delivery system in Pengshui County, focusing on the design and implementation of the horizontal integrated-care model, as well as its financial mechanisms. A descriptive, explanatory, evaluative case study was conducted based on analysis of national and local policy documents, in-depth interviews with local policy makers and institution managers in March, 2019, and analysis of pre-reform and post-reform administrative data from provincial and local health administrative departments. Implementation of the reform was characterised by establishment of a commission of primary care and a policy-coordinating board, which was charged with managing all horizontally integrated primary care providers and strengthening strategic planning and management of Pengshui County's primary care system. Additionally, a primary care funding pool was developed to support facility purchasing, professional development, and financial incentives. The reform was also characterised by performance assessments, with equal emphasis on public health care and basic medical services, and an enhanced compensation system to encourage uptake of grassroots medical posts by the primary care workforce. From 2009 to 2018, the number of primary care health professionals increased by 125% (from 1113 to 2510). The proportion of outpatients who sought first-contact care in rural community health centres or township health centres increased from 29% (522 700 of 1 817 600) in 2009 to 40% (849 900 of 2 147 800) in 2018 (the national average in 2018 was 23%). From 2009 to 2018, the proportion of inpatients in primary medical institutions decreased slightly from 67% (30 528 of 45 450) to 60% (93 273 of 156 166), marking a decline rate that was 6 percentage points lower than the national average (the national average decreased from 31% to 17%). However, numbers of inpatients tripled in the same period. The mean annual payment to primary care staff was ¥120 800 (SD 25 615) in 2018, which was five times higher than in 2009. Our study suggests that a high priority of Pengshui County's reform strategy was the mobilisation of enough resources to finance efficient and equitable provision of primary care. The horizontal integrated-care model established a clear division of responsibilities and governance structure. The policy of fundraising and mutual aid-sharing of compulsory payment improved the financing and compensation mechanism and made up for the problem of insufficient investment. Many positive results have been achieved through the reform, including advanced medical facilities, more qualified medical professionals, better capability of primary health care, and improved patients' trust of public health and primary medical services. Pengshui County's experience represents a successful experiment in the development of integrated-care reform, especially for rural and low-income regions. World Bank China and Science and Technology Department of Chongqing. [ABSTRACT FROM AUTHOR]

Seven undescribed C21 steroids, namely cynanchin A – G , together with thirteen known analogues, were isolated from the roots of cynanchum otophyllum. Their structures were elucidated by 1D, 2D NMR and MS spectra, as well as chemical methods. Meanwhile, all of isolates were tested for their anti-hepatic fibrosis activity. Among them, compounds 4–6 , 10–12 and 14–17 showed moderate or significant inhibitory effects for the proliferation of hepatic stellate cells (HSCs) induced by transforming growth factor- β 1 (TGF- β 1) in vitro. Seven undescribed steriods together with thirteen known compounds were isolated from the roots of Cynanchum otophyllum. Some of them showed moderate or marked anti-hepatic fibrosis activity. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract: Mutations of 3 causative genes, namely presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP), have been identified as the major causes of early-onset familial Alzheimer's disease (EOFAD). Recently, a GGGGCC repeat expansion in the noncoding region of C9orf72 was also detected in some patients with clinically diagnosed familial Alzheimer's disease. The prevalence of causative gene mutations in patients with EOFAD has been reported in previous studies but their prevalence remains unclear in Mainland China. The aim of this study was to characterize the common causative gene mutation spectrum and genotype-phenotype correlations in Chinese patients with EOFAD. Genetic screening for mutations in PSEN1, PSEN2, and APP was conducted in a total of 32 families with clinical diagnoses of EOFAD from Mainland China. Subsequently, a hexanucleotide repeat expansion in C9orf72 was detected in all patients. Four novel mutations in PSEN1 (p.A434T, p.I167del, p.F105C, and p.L248P) were identified in 4 respective families, and 1 previously recognized pathogenic mutation in APP (p.V717I) was detected in another 2 unrelated families. The PSEN2 mutation and pathogenic repeat expansions of C9orf72 were not detected in all patients. To the best of our knowledge, this is the first cohort report of a causative gene screen in patients with EOFAD in Mainland China. The analysis of the genetic-clinical correlations in this cohort supports the idea that the clinical phenotype might be influenced by specific genetic defects. [Copyright &y& Elsevier]