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The potential mechanism of mulberry leaf against type 2 diabetes mellitus (T2DM) is not fully elucidated. Here, we hypothesized that the anti-T2DM of mulberry leaf ethanol extract (MLEE) is related to improvement of gut microbiota and bile acids (BAs) metabolism. Our results showed that MLEE alone can ameliorate glycolipid metabolism disorder, insulin resistance, and inflammation in db/db mice, and presents synergistic effects with metformin (MET). Furthermore, we found that MLEE altered the abundances of gut microbiota related to BAs metabolism such as Colidextribacter, Muribaculum, Muribaculaceae, and Eubacterium_siraeum_group, promoted fecal ωMCA level and thus inhibited intestinal farnesoid X receptor (FXR) gene expression, and then increased plasma glucagon-like peptide-1 (GLP-1) level. Furthermore, intestinal FXR inhibition and plasma GLP-1 level enhancing of MLEE could also be observed in antibiotic-intervened db/db mice. These results indicated that MLEE could alleviate T2DM via gut microbiota-BAs-intestinal FXR pathway mediated by gut microbiota and host.

Abstract An investigation about localized CP asymmetries for the processes of $${\bar{B}}_{s}^{0} \rightarrow \pi ^{+}\pi ^{-}\pi ^{0} (K^{0})$$ B ¯ s 0 → π + π - π 0 ( K 0 ) is presented in this paper. The innovation of this paper is that there is a consideration of three-particle $$\rho ^0(770)$$ ρ 0 ( 770 ) , $$\omega (782)$$ ω ( 782 ) and $$\phi (1020)$$ ϕ ( 1020 ) interferences effect. Generally, $$\omega (782)$$ ω ( 782 ) and $$\phi (1020)$$ ϕ ( 1020 ) both can decay into $$\pi ^+\pi ^-$$ π + π - pair where can cause extremely small contribution from isospin symmetry breaking. Nevertheless, our analysis shows that $${\bar{B}}_{s}^{0} \rightarrow \pi ^+\pi ^-\pi ^{0}(K^{0})$$ B ¯ s 0 → π + π - π 0 ( K 0 ) decay process can bring differential CP asymmetry about $$65\%$$ 65 % ( $$36\%$$ 36 % ) because of isospin symmetry breaking. To be better compared with the data from experimental in the future, we integrate CP asymmetry over the invariant mass and obtain localized CP asymmetry value for the decay $${\bar{B}}_{s}^{0} \rightarrow \pi ^+\pi ^-\pi ^{0} (K^{0})$$ B ¯ s 0 → π + π - π 0 ( K 0 ) . We find that there is an evident signal about CP asymmetry at invariant mass value $$m(\pi ^{+}\pi ^{-})$$ m ( π + π - ) below the mass of $$\rho ^{0}(770)$$ ρ 0 ( 770 ) with the decay $${\bar{B}}_{s}^{0} \rightarrow \pi ^+\pi ^{-}\pi ^{0}$$ B ¯ s 0 → π + π - π 0 .

In the marine environment far away from the mainland, the coral sand foundation can be improved by injecting the cement grout with a very small amount of graphene oxide (GO) through grouting or mixing piles and other processes, which can greatly increase the stone body’s ability to block chloride ion penetration. Based on the comparative analysis of the difference in the particle morphology of river sand and coral sand and changes in hydration products and microstructure before and after GO incorporation, this study employed a rapid chloride ion migration test, scanning electron microscope experiment, and Image-Pro Plus image processing to reveal the mechanism of the modified coral sand cement stone body blocking permeation by chloride. The result reveals that high particle angles, irregular shapes, and porous and internal pores are the main reasons for the lower coral sand cement stone body than the river sand cement stone body in blocking chloride ion permeability under the same process conditions. After mixing 0.02% (mass fraction) GO, 28 d and 56 d coral sand cement stones have the highest degree of improvement in blocking chloride ion permeability (39.43% and 48.93%) and are similar to those of ordinary river sand cement stones without GO addition under the same process conditions. The coral sand cement stone body’s antichloride ion penetration performance improvement is related to the amount of GO. The two are first positively correlated and then negatively correlated. 0.02% is the best mix-up measure after the experiment in the assay. Regulating cement hydration products to form a regular and orderly hydrated crystal shape, improving the morphology of the interface transition zone, filling the space of internal cracks, and repairing the morphological characteristics of the pores are the main reasons that allow the incorporation of GO to affect the resistance of coral sand cement stones to chloride ion permeability.

Abstract Background Tuberculosis (TB) poses a severe public health challenge in China and worldwide. This study evaluated the effects of age, period, and birth cohort on reported incidence trends of TB based on population and refined the characteristics of high-risk groups. Methods Aggregate data that reported pulmonary tuberculosis (PTB) cases from China Tuberculosis Management Information System (TBIMS) from 2006 to 2020 were used to analyze effect coefficients through the age–period–cohort (APC) model based on intrinsic estimator (IE) method, and converted them into relative risk (RR) to estimate trends. Results A total of 14.82 million cases of PTB were reported in China from 2006 to 2020, showing a continuous downward trend. The reporting rate increased with age by age group, with 70–74 years old being 2–3 times higher than that in 20–24 years old. APC analysis model showed that age effects were bimodal in 20–24 years old [RR = 2.29, 95% confidence interval (CI): 1.73–3.03] and 70–74 years old (RR = 1.95, 95% CI: 1.67–2.27), and lower than the overall average in the groups under 15 years old. Stratified results showed that the risk was higher for women under age 40 than men and higher for men over 40. The risk was higher in urban than in rural areas under 30 years old and slightly higher in rural than in urban between 30 and 64 years old. The risk for 15–34 years old was significantly higher in the east than in other regions. The period effects showed a decreasing trend, and the risk was higher in rural in recent years. Except for cohorts born in 1961–1965 and 2001–2005, where the RR increased, the later the cohort was born, the lower the risk. The cohort 1926–1930 in eastern had the highest risk (RR = 3.49, 95% CI: 2.44–4.98). Conclusions The reported incidence of PTB continued to decline in China from 2006 to 2020. The young (20–24 years old) and the elderly (70–74 years old) were equally at high risk. There were differences in the age, period and cohort effects on PTB incidence among gender, urban–rural and regions. Our findings better reflected the characteristics of high-risk populations, thus contributing to the development of timely and effective intervention strategies, and providing clues for etiological research. Graphical abstract

The air-lifting pump has the advantages of low cost, strong reliability, simple structure and convenient maintenance, especially in the fields of deep-sea mining, oilfield mining and mineral mining under complex geological conditions. The construction technology and air intake mode not only play a decisive role in the performance of the air-lifting pump, but also greatly hinder the engineering application of the air-lifting pump. Here, the air-lifting pump is taken as the research object, and the river sand is used as the experimental transport medium. The particle concentration-efficiency model is established based on the mechanical energy conservation theorem. The working performance characteristic parameters of the air-lifting pump under different construction technologies are obtained by a three-axis motion control system. On this basis, the working performance characteristic parameters of the air-lifting pump under different intake modes are obtained by changing the intake mode. The results show that the particle concentration-efficiency model can well describe the efficiency of lifting solid particles by the air-lifting pump. When the sand depth is less than 200 mm, the concentration and efficiency of solid particles transported by the air-lifting pump in the horizontal movement construction are significantly better than those in the fixed position construction. In the same construction technology, the solid particle concentration of the air-lifting pump in uniform intake mode is better than that in non-uniform intake mode, while the transportation efficiency of the air-lifting pump in non-uniform intake mode is better than that in uniform intake mode. The research results of this paper can provide an important theoretical reference value for the air-lifting pump in practical engineering applications.

Background/purpose: The World Health Organization has recommended commercial urine-sourced lipoarabinomannan (LAM) detection as a tool for screening HIV patients with suspected TB, but more sensitive immunodetection assays would help to identify HIV-negative TB patients. Here, we aimed to develop novel rabbit monoclonal antibodies (mAbs) against LAM for immunodetection purposes. Methods: Rabbits were immunized with cell-wall components from the Mycobacterium tuberculosis (Mtb) H37Rv strain. An immune single-chain fragment variable (scFv) phage display library was generated. The scFv mAbs to LAM were identified through ELISA screening. The light and heavy chain variable region genes from the selected clones were sequenced. Vectors containing the full-length light and heavy chains were constructed and co-expressed in 293 T cells to generate whole IgG antibodies. The performances and binding characteristics of the mAbs against purified LAM from M.tb H37Rv, multiple mycobacteria species (M.tb H37Rv, M. bovis and non-tuberculous mycobacteria (NTM) strains), and mycobacteria clinical isolates (Mtb and NTM isolates) were determined using various immunoassay methods. Results: We obtained five rabbit mAbs against LAM, four of which had high sensitivities (100 pg/ml) and affinities (1.16–1.73 × 10−9 M) toward LAM. They reacted with M.tb H37Rv, M. bovis, and slow-growing NTM, but not with rapid-growing NTM. Similar results were obtained with mycobacterium isolates, where 96% of the Mtb isolates and 90% of the M. avium-intracellulare isolates were successfully identified. Conclusion: The novel rabbit LAM-specific mAbs performed well at recognizing LAM from slow-growing pathogenic mycobacteria, which support their future clinical application.

Abstract Background Information on the prevalence and resistance spectrum of nontuberculous mycobacteria (NTM) in China is mainly based on regional or local data. To estimate the proportion of NTM cases in China, a national survey of NTM pulmonary disease was carried out based on acid-fast positive sputum samples collected in 2013. Methods Sputum samples collected from enrolled presumptive cases in 72 nationwide tuberculosis surveillance sites from the 31 provinces in the mainland of China were cultured using L-J medium at the National tuberculosis reference laboratory (NTRL). MALDI-TOF MS identified the species of re-cultured strains, and minimal inhibitory concentrations (MICs) were determined to evaluate the drug susceptibility of NTM isolates. Data analysis used statistical software SPSS version 22.0 for Windows statistical package. Results Of 4917 mycobacterial isolates cultured, 6.4% [317/4917, 95% confidence interval (CI) 5.8%–7.2%] were confirmed as NTM, among which 7.7% (287/3709, 95% CI 6.9%–8.6%) were from the southern region. In inland and coastal China, 87.7% (95% CI 78.7%–93.2%) and 50.0% (95% CI 43.7%–56.3%) of isolates, respectively, were slow-growing mycobacteria (SGM), with the remaining rapid growing mycobacteria (RGM). A total of 29 species were detected, Mycobacterium abscessus had higher clarithromycin-inducible resistance rates than M. massiliense (65.67% vs 2.22%). M. kansasii presented lower resistance rates in linezolid and moxifloxacin than M. avium-intracellulare complex (3.23% vs 66.67%, 0 vs 47.22%) and other SGM (3.23% vs 38%, 0 vs 26%). Conclusions More NTM pulmonary disease was observed in the south and coastal China (P

Abstract Background China is still faced with the public health challenge of tuberculosis (TB), and a robust surveillance system is critical for developing evidence-based TB control policies. The Tuberculosis Information Management System (TBIMS), an independent system launched in 2005, has encountered several challenges in meeting the current needs of TB control. The Chinese government also planned to establish the National Health Information System (NHIS) aggregating data in different areas. The China National Health Commission-Gates TB Project Phase III launched a new TB surveillance system to address these challenges and also as a pilot for the countrywide implementation of the NHIS. This commentary highlights the improvements and challenges in implementing the new TB system and also discusses the implications for the roll-out of the NHIS. Main text The new TB surveillance system piloted in each prefecture of the project provinces was designed based on the local information system under the unified principle of organizing patient information under a unique ID and realizing the function of data exchange. Upon mid-2019, the data exchange successful rate reached almost 100%, and the system showed good performance in data completeness. Major improvements of the new system included achieving automatic data extraction instead of manual entry, assisting clinical service provision, and the augmented statistical functions. The major challenges in the implementation and scale-up of the new system were the licensing issue and the diversities of infrastructures that hinder the promotion of the new system at a low cost. This pilot also accumulated experiences for the roll-out of the NHIS regarding the technical solutions of reforming current information systems as well as effective training approaches for the developers and users of the new system. Conclusions The successful implementation of the new TB surveillance system in the three TB designated medical institutions demonstrated how the diverse infrastructures of the information system could be reformed to achieve the functions of automatic data extraction and data exchange and better cater to the needs of healthcare workers. This pilot also accumulated rich experiences and lessons learnt for developing technical solutions and personnel training for the scale-up of the NHIS.

Abstract Background In China, an indigenously developed electronic medication monitor (EMM) was designed and used in 138 counties from three provinces. Previous studies showed positive results on accuracy, effectiveness, acceptability, and feasibility, but also found some ineffective implementations. In this paper, we assessed the effect of implementation of EMMs on treatment outcomes. Methods The longitudinal ecological method was used at the county level with aggregate secondary programmatic data. All the notified TB cases in 138 counties were involved in this study from April 2017 to June 2019, and rifampicin-resistant cases were excluded. We fitted a multilevel model to assess the relative change in the quarterly treatment success rate with increasing quarterly EMM coverage rate, in which a mixed effects maximum likelihood regression using random intercept model was applied, by adjusting for seasonal trends, population size, sociodemographic and clinical characteristics, and clustering within counties. Results Among all 69 678 notified TB cases, the treatment success rate was slightly increased from 93.5% [95% confidence interval (CI): 93.0–94.0] in second quarter of 2018 to 94.9% (95% CI: 94.4–95.4) in second quarter of 2019 after implementing EMMs. There was a statistically significant effect between quarterly EMM coverage and treatment success rate after adjusting for potential confounders (P = 0.0036), increasing 10% of EMM coverage rate will lead to 0.2% treatment success rate augment. Besides, an increase of 10% of elderly or bacteriologically confirmed TB will lead to a decrease of 0.4% and 0.9% of the treatment success rate. Conclusions Under programmatic settings, we found a statistically significant effect between increasing coverage of EMM and treatment success rate at the county level. More prospective studies are needed to confirm the effect of using EMM on TB treatment outcomes. We suggest performing operational research on EMMs that provides real-time data under programmatic conditions in the future.

Abstract Background Host genetic factors affect the immune response to Mycobacterium tuberculosis (Mtb) infection as well as the progression of the disease. Epiregulin (EREG) belongs to the epidermal growth factor (EGF) family, which binds to the epidermal growth factor receptor (EGFR) to regulate the immune response of the host during infections. Our study aimed to compare EREG levels in tuberculosis (TB) patients and healthy controls and assess whether polymorphisms in EREG increase the risk of TB. Methods We used ELISA to determine the plasma EREG level from 30 healthy controls and 50 tuberculosis patients. By evaluating the EREG gene from 624 TB patients and 600 healthy controls, we determined the allelic and genotypic frequencies for association with susceptibility to TB infections in this group. Results This paper shows that the pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) groups showed a significantly higher plasma EREG level (1014 ± 733.9 pg/ml, 700.2 ± 676.6 pg/ml, respectively) than the healthy controls (277 ± 105.4 pg/ml). The rs2367707 polymorphism was associated with a higher risk of PTB and EPTB (P = 0.00051, P = 0.0012). Analyses of haplotype frequencies found that people with the haplotype CACAT had a higher risk of PTB and EPTB (P = 0.00031, OR = 1.43; P = 0.000053, OR = 1.65). Moreover, the rs6446993 polymorphism of the EREG gene was found to be associated with EPTB (P = 0.00087, OR = 1.54; 95% CI = 1.23–1.94). Conclusions Compared to that of healthy controls, the level of EREG in the plasma of TB patients increased significantly. Based on these data, we demonstrated that EREG polymorphisms are genetic factors for susceptibility to TB and various forms of TB.

Abstract Background China is one of 22 countries with a high tuberculosis (TB) burden in the world. Healthcare workers (HCWs) have a high risk of contracting Mycobacterium tuberculosis infection due to insufficient infection control practices. We conducted a cross-sectional study to explore the prevalence of TB and its associated risk factors among HCWs in Chinese TB facilities. Methods Two hundred and forty-one TB facilities employing a total of 9663 HCWs were selected from 12 provinces in China to represent healthcare settings at the provincial, prefectural, and county levels. Structured questionnaires were used to collect information on TB infection control practices and HCWs in those facilities. Data was double entered into EpiData 3.1; TB prevalence and associated risk factors were analyzed using SPSS 21.0 with bivariate and multivariate regression models. Results The results showed that 71 HCWs had been diagnosed with TB, accounting for a prevalence of 760/100 000. The multivariate analysis showed that associated risk factors included belonging to the age group of 51 years and above (aOR: 6.17, 95% CI: 1.35–28.28), being a nurse (aOR = 3.09, 95% CI: 1.15–8.32), implementation of 0–9 items of management measures (aOR = 2.57, 95% CI: 1.37–4.80), and implementation of 0–1 items of ventilation measures (aOR = 2.42, 95% CI: 1.31–4.47). Conclusion This was the first national large sampling survey on TB prevalence among HCWs in China. It was found that the implementation of TB infection control practices in some facilities was poor. The TB prevalence in HCWs was higher than that in the general population. Therefore, TB infection control practices in Chinese medical facilities should be strengthened.

Based on a 2D discrete element method (PFC2D code) and limit equilibrium method, a new method is proposed to obtain critical slip surface and to determine the factor of safety of the slope model. After the calibration process, the excavation process on the rectangular assembly of particles can make the slope model of the DEM. As the trial acceleration of gravity increases, the critical slip surface tends to change from shallow to deep, which indicates more serious failures in the slope. With higher trial accelerations of gravity, the factor of safety calculated by this method continually increases as well. Therefore, the critical trial acceleration of gravity that places the slope in a critical state of failure is essential to ensure the results are correct. The gravity increase method is applied to render the critical state of failure for slope model. As soon as the continuous failure surface forms, the influence parameters of particles on the critical slip surface also can be determined. Connecting the centre of these particles forms the critical slip surface, which is more consistent with the actual situation in nature due to the absence of assumptions of the critical slip surface in this method. Then, the factor of safety is calculated by the Spencer method that has the ability of dealing with noncircular, complex slip surface. This method proves to be a promising tool to analyse slope stability with the DEM. The character of progressive failure process of slope can be well modelled by DEM by investigating the development of failure in the slope body. By studying temporal and spatial risk of slope instability by the total failure process, it is possible for managers and engineers to detect temporal and spatial risks so robust suggestions and mitigation measures can be made.

Objectives: To evaluate the performance of the newly developed technology Abbott RealTime MTB assay (RealTime MTB assay) for the detection of Mycobacterium tuberculosis in sputum specimens and to compare its performance with that of the Cepheid GeneXpert assay. Methods: Sputum specimens were collected from 270 subjects suspected to have tuberculosis (TB). Smear microscopy, culture, identification, RealTime MTB, and GeneXpert assays were performed according to standard protocols. Accuracy measures of the method evaluated were determined using solid culture as the reference standard. Results: The RealTime MTB assay showed similar positive detection rates as the GeneXpert assay in smear-positive, culture-positive, and smear/culture-negative groups; no significant differences were found in these groups between the two assays. The RealTime MTB assay demonstrated a sensitivity of 100% and a specificity of 84.4%; the GeneXpert assay had a sensitivity of 96.9% and specificity of 89.6%. After the resolution of discordant results by PCR-based molecular method, the sensitivities and specificities of the RealTime MTB and GeneXpert assays were 100% vs. 97% and 90.0% vs. 95.6%, respectively; no significant difference in sensitivity or specificity was found between the RealTime MTB and GeneXpert assays. Conclusions: This study demonstrated that the Abbott RealTime MTB and Cepheid GeneXpert assays have similar sensitivity and specificity. The Abbott RealTime MTB assay is a highly promising method for the diagnosis of TB.

Background: Microbiological confirmation of tuberculous meningitis (TBM) remains problematic. We assessed the diagnostic performance of a modified Ziehl-Neelsen (MZN) staining method that showed promise in earlier studies. Methods: Patients evaluated for TBM in Shaanxi province, China, were prospectively enrolled from May, 2011 to April, 2013. Cerebrospinal fluid (CSF) specimens were evaluated using the Xpert MTB/RIF® assay, MZN staining, and standard biochemical and microbiological tests, together with detailed clinical and radiological assessment. Results: Among 316 patients included in the study, 38 had definite TBM, 66 probable TBM, 163 possible TBM and 49 "no TBM," using consensus uniform research case definition criteria. Comparing "definite or probable TBM" to "no TBM" MZN staining had higher sensitivity than Xpert MTB/RIF® (88.5 vs. 36.5%), but greatly reduced specificity (71.4 vs. 100.0%); 14/49 (28.6%) cases with "no TBM" tested positive on MZN. Mycobacterium tuberculosis culture was performed in 104/179 (58.1%) of MZN positive samples; 12.5% (13/104) were positive. Using Xpert MTB/RIF® as the reference standard, MZN had a sensitivity of 92.1% (95% CI 79.2-97.3) and specificity of 71.4% (95% CI 57.6-82.2). Conclusion: Xpert MTB/RIF® offered a rapid and specific TBM diagnosis, but sensitivity was poor. MZN was mainly hampered by false positives. Strategies to enhance the sensitivity of Xpert MTB/RIF® or improve the diagnostic accuracy of MZN should be explored. [ABSTRACT FROM AUTHOR]