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Background Herbal Reference Extracts (HREs) have been used for the overall quality control (QC) of Traditional Chinese Medicines (TCMs) and used as an effective strategy for solving the shortage of reference standards in quality evaluation of TCMs in recently years. But the preparation and evaluation of it has rarely been reported. The ideal HREs should be a combination of Chemical Reference (CR) and Efficacy Reference (ER). However, it is not realistic to achieve "completely extracted" of TCMs at the present stage. Quality markers (Q-markers) provides a series of effective and scientific strategies for QC of TCMs. And Q-markers-based HREs should be a meaningful attempt to promote the standardization of quality evaluation system for TCMs. Purpose Preparation adequate HREs based on the principles of Q-markers, and used for quality evaluation of relevant preparation products. Then propose the general procedure for establishing HREs used for identification. Methods The authenticity, specificity, consistency and stability (ASCS) were the four essential principles of HREs. In this study, we chose Aurantii Fructus as an example, Firstly, selected 7 Q-markers of it which has the properties of specificity, effectiveness and testability based on the combination of analytic hierarchy process and entropy weight method (AHP-EWM). Secondly, preparated its reference extract which is called Orange Fruit Reference Extract (OFRE) based on ASCS and its Q-markers. Thirdly, established the QC method of OFRE according to its usage requirements. And finally, demonstrated its application of the thin layer chromatography (TLC) identification and characteristic chromatogram identification in the Orange fruit formula granule (or called Zhiqiao Peifangkeli, ZQPK). Results Compared with the Herbal Reference Substance (HRS) which with characteristic appearance or morphological structure, OFRE can be used for TLC identification of ZQPK conveniently, without complicated extraction or purification steps. And in the analysis of characteristic chromatogram of ZQPK, the OFRE can provid a rather simple profile, the main naringin, neohesperidin, nobiletin and tangeretin were clearly separated, which indicated that the OFRE could be used to identify the characteristic chromatogram of ZQPK and reduce the use of Chemical Reference Substance (CRS). And finally, we propose the general procedure for establishing HREs used for identification. Conclusion In summary, Q-markers-based HREs is feasibility, and should have a broader application prospect. And this research concept can serve as a reference for study on preparation, evaluation and application of HREs used for identification.

Additional file 2: Deterministic risk assessment results for heavy metals in TCM.

Additional file 3: Table S1. HBGV of heavy metals from different sources.

Background: Liver fibrosis involves the increase of iron deposition. however, whether R2* measurement can be used as a noninvasive method to characterize processes of fibrogenesis with iron deposition is not clear. This study aims at assessing the usefulness of magnetic resonance imaging (MRI) R2* value in diagnosing and staging of rat liver fibrosis. Methods: Male Sprague-Dawley rats were injected intraperitoneally with a mixture of 1.0 ml/kg carbon tetrachloride (CCl4) and oil (1:1 v/v) twice a week for 12 weeks. Liver R2* value was quantitatively determined by multi - echo fast gradient echo sequence. Liver iron content (LIC) was evaluated by an atomic absorption spectrophotometer. The stage of liver fibrosis was assessed by pathological METAVIR scores. The performances of R2* values for each fibrosis stage were evaluated. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values for fibrosis stage. Results: R2* values and LIC gradually increased during the progression of the liver fibrosis, the correlation between the R2* values and the LIC was high-positive. There were significant differences in R2* values among the stages of liver fibrosis (F= 30.84，P < 0.001). There was a significant positive correlation between R2* values and LIC (r= 0.984, P < 0.001). The most discriminating cutoff values of R2* were 46.84 Hz for ≥ F1, 55.30 Hz for ≥ F2, 68.06 Hz for ≥ F3, and 78.79 Hz for F4. Conclusion: R2* values can be used for detecting and staging liver fibrosis. The degree of liver fibrosis was related to the degree of increase in R2* measurements.

Background Renal schwannomas are very rare and are usually benign. Its clinical symptoms and imaging features are nonspecific, and the diagnosis is usually confirmed by pathology after surgical resection. Case presentation A 46-year-old Chinese female was admitted to the hospital with right flank pain that had persisted for the six months prior to admission. This pain had worsened for 10 days before admission, and dyspnea occurred when she was supine and agitated. A right abdominal mass could be palpated on physical examination. Computed tomography and magnetic resonance imaging examinations revealed a large, nonenhanced, cystic and solid mass in the right kidney. The patient received radical nephrectomy for the right kidney. The diagnosis of schwannoma was confirmed by pathological examination. Conclusions We report a case of a large renal schwannoma with obvious hemorrhage and cystic degeneration, which can be used as a reference for further study.

Excessive nitrogen (N) fertilization with a high basal N ratio in wheat can result in lower N use efficiency (NUE) and has led to environmental problems in the Yangtze River Basin, China. However, wheat requires less N fertilizer at seedling growth stage, and its basal N fertilizer utilization efficiency is relatively low; therefore, reducing the N application rate at the seedling stage and postponing the N fertilization period may be effective for reducing N application and increasing wheat yield and NUE. A 4-year field experiment was conducted with two cultivars under four N rates (240 kg N ha−1 (N240), 180 kg N ha−1 (N180), 150 kg N ha−1 (N150), and 0 kg N ha−1 (N0)) and three basal N application stages (seeding (L0), four-leaf stage (L4), and six-leaf stage (L6)) to investigate the effects of reducing the basal N application rate and postponing the basal N fertilization period on grain yield, NUE, and N balance in a soil-wheat system. There was no significant difference in grain yield between the N180L4 and N240L0 (control) treatments, and the maximum N recovery efficiency and N agronomy efficiency were observed in the N180L4 treatment. Grain yield and NUE were the highest in the L4 treatment. The leaf area index, flag leaf photosynthesis rate, flag leaf nitrate reductase and glutamine synthase activities, dry matter accumulation, and N uptake post-jointing under N180L4 did not differ significantly from those under N240L0. Reduced N application decreased the inorganic N content in the 0–60-cm soil layer, and the inorganic N content of the L6 treatment was higher than those of the L0 and L4 treatments at the same N level. Surplus N was low under the reduced N rates and delayed basal N application treatments. Therefore, postponing and reducing basal N fertilization could maintain a high yield and improve NUE by improving the photosynthetic production capacity, promoting N uptake and assimilation, and reducing surplus N in soil-wheat systems.

Breast cancer is a severe threat to the health and lives of women due to its difficult early diagnosis and the unsatisfactory therapeutic efficacy of breast cancer treatments. The development of theranostic strategies to combat breast cancer with high accuracy and effectiveness is therefore urgently needed. In this study, we describe a near-infrared (NIR) light-controllable, targeted and biocompatible drug delivery nanoplatform (PFH-PTX@PLGA/SPIO-Her) for photoacoustic (PA)/ultrasound (US) bimodal imaging-guided photothermal (PTT)/chemo synergistic cancer therapy of breast cancer. Carboxyl-modified PEGylated poly (lactic-co-glycolic acid) (PLGA-PEG-COOH) constituted the skeleton of the nanoplatform. Especially, the antibody Herceptin was modified onto the surface of nanoplatform for active HER2-targing to facilitate the tumor accumulation of the nanoplatform. The encapsulated superparamagnetic iron oxide (SPIO) nanoparticles could be employed as an excellent PA imaging agent to guide tumor therapy. When exposed to NIR light, the SPIO also could transform NIR light into thermal energy for photothermal ablation of tumor. The NIR-induced thermal effect subsequently triggered the optical droplet vaporization (ODV) of perfluorohexane (PFH) to generate PFH gas bubbles, which not only achieved the US imaging enhancement, but also contributed to the release of loaded paclitaxel (PTX) from the nanoplatform for significantly improving PTT therapeutic efficacy. Our results demonstrated that the targeted tumor accumulation, accurate real-time bimodal imaging, and the abundant drug release at the tumor site were all closely associated with the PTT therapeutic efficacy. Therefore, the theranostic nanoplatform is a very promising strategy for targeted imaging-guided photothermal/chemo synergistic tumor therapy with high therapeutic efficacy and minimized side effects. STATEMENT OF SIGNIFICANCE: Breast cancer is the most frequent cancer in women. Herein, we successfully developed a light-controllable and HER2 targeted theranostic nanoparticels (PFH-PTX@PLGA/SPIO-Her) as a specific drug delivery nanoplatform to overcome the low accuracy of tumor detection and the low specificity of traditional chemo-therapeutic protocols. The study demonstrated that PFH-PTX@PLGA/SPIO-Her could actively target to breast cancer cells with positive HER2 expression. The biocompatible PFH-PTX@PLGA/SPIO-Her nanoparticles as both photoacoustic/ultrasound bimodal imaging agents, photothermal-conversion nanomaterials (photothermal hyperthermia) and controllable drug delivery nanoagents (optical droplet vaporization) have completely eradicated the tumor without severe side effects. The theranostic strategy not only integrates strengthens of traditional imaging or therapeutic modalities, but also paves a new way for the efficient cancer treatment by taking the advantage of quickly-developing nanomedicine.

Aims To determine how long SARS-CoV-2 virus RNA persists in fecal specimens in children with COVID-19. Methods Retrospectively, ten children with confirmed COVID-19 in the Jinan Infectious Disease Hospital Affiliated to Shandong University were enrolled between January 23, 2020 to March 9, 2020. Epidemiological, clinical, laboratory, and radiological characteristics of the children were analyzed. RT-PCR assays were performed to detect the SARS-CoV-2 virus RNA in the respiratory tract and fecal specimens in the follow-up after discharge. Results Among ten patients, five (50%) were asymptomatic and five (50%) showed mild symptoms of respiratory illness. The average age of asymptomatic children was younger than that of symptomatic children (p = 0.03). The decreases in white blood cell (WBC) (p = 0.03) and lymphocyte (p = 0.03) counts were more severe in symptomatic patients than those in asymptomatic patients. During the follow-up examination after discharge, seven out of ten patients contained SARS-CoV-2 virus RNA in their fecal specimens, despite all patients showed negative results in respiratory tract specimens. One out of those seven patients relapsed. The median time from onset to being negative results in respiratory tract and fecal specimens was 9 days and 34.43 days, respectively. Conclusions SARS-CoV-2 virus RNA persists much longer in the gastrointestinal (GI) tract than that in respiratory tract.

Aims & background: IFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1β. However, the role of IFI16 in regulating the immune response to viruses in vivo and in vitro, especially in sensing hepatitis B virus (HBV), has not been examined. We hypothesized that the expression of IFI16 increases corresponding to HBV-mediated inflammation in patients with hepatitis B virus associated glomerulonephritis (HBV-GN), a condition which activates inflammatory mechanisms and causes renal damage. To test this hypothesis, we therefore analyzed the expression of IFI16 and inflammatory factors in HBV-GN tissues and cell lines relative to the inflammatory response to HBV infection. Methods: A total 75 patients with chronic nephritis(CN) including 50 with HBV-GN and 25 with chronic glomerulonephritis (CCN) involved in this study. Each CN patient received renal biopsy, and immunohistochemistry(IHC) was used to detect the expression of IFI16 and inflammatory factors Caspase-1 and IL-1β in the biopsy specimens. Following IFI16 was transfected in HBV-infected and HBV-uninfected human glomerular mesangial (HGM) cell line and HEK-293T cell line, expression of Caspase-1 and IL-1β were detected by Western blot and qRT- PCR. Results: IFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and positively correlated with caspase-1 and IL-1𝛽 expression in HBV-GN. In vitro, over expression IFI16 increased caspase-1 and IL-1𝛽 expression in HBV -infected HGM and HEK-293T. Conclusions: The elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.

Under the circumstances of rapid expansion of diverse forms of volatile and intermittent renewable energy sources, hydropower stations have become increasingly indispensable for improving the quality of energy conversion processes. As a consequence, Francis turbines, one of the most popular options, need to operate under off-design conditions, particularly for partial load operation. In this paper, a prototype Francis turbine was used to investigate the pressure fluctuations and hydraulic axial thrust pulsation under four partial load conditions. The analyses of pressure fluctuations in the vaneless space, runner, and draft tube are discussed in detail. The observed precession frequency of the vortex rope is 0.24 times that of the runner rotational frequency, which is able to travel upstream (from the draft tube to the vaneless space). Frequencies of both 24.0 and 15.0 times that of the runner rotational frequency are detected in the recording points of the runner surface, while the main dominant frequency recorded in the vaneless zone is 15.0 times that of the runner rotational frequency. Apart from unsteady pressure fluctuations, the pulsating property of hydraulic axial thrust is discussed in depth. In conclusion, the pulsation of hydraulic axial thrust is derived from the pressure fluctuations of the runner surface and is more complicated than the pressure fluctuations.

Objectives: In China, the epidemic pattern of acute hepatitis E virus (HEV) infection has changed from waterborne outbreaks to foodborne sporadic cases. However, the clinical course of sporadic acute hepatitis E (AHE) has not been well defined. Methods: Consecutive patients with AHE who were admitted to the Jinan Infectious Disease Hospital, Jinan, Shandong Province between January 2003 and December 2014 were evaluated and followed. Demographic data, clinical manifestations, results of laboratory tests, and outcomes were recorded. Risk factors for liver failure and death were analyzed. Results: A total of 680 patients with AHE were identified during the study period. The incidence was highest in February, March, and April, accounting for about 41% of the cases. The male to female ratio was 5.1:1 (574/106). The average age was 50.9 ± 12.8 years. The prevalence rates of prodromal fever, fatigue, loss of appetite, and jaundice were 25.6%, 85.6%, 83.8%, and 92.8%, respectively. The median (range) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, and platelet levels were 727 (8–6270) U/l, 300 (17–6226) U/l, 196.8 (8.0–1083) μmol/l, 33.0 (15.2–45.8) g/l, and 162 (10–589) × 109/l, respectively. The prevalence of hepatitis B surface antigen (HBsAg) was 18.5% (126/680) and of liver cirrhosis was 9.4% (64/680). Thirteen percent (89/680) of the cases progressed to liver failure, including 4.1% (28/680) with acute liver failure (ALF) and 9.0% (61/680) with acute-on-chronic liver failure (ACLF). Among patients with HBsAg positivity or cirrhosis, 28.6% (36/126) and 36.0% (23/64), respectively, progressed to ACLF. Multiple logistic regression analysis indicated that age >53 years, prodromal fever, HBsAg positivity, cirrhosis, and thrombocytopenia (platelet count 500 μmol/l, international normalized ratio (INR) >2, and severe thrombocytopenia (platelet count

Additional file 1. Minimum Standards of Reporting Checklist.

Additional file 3. The minimum standards of reporting checklist.

Type 2 diabetes has been suggested as an independent risk factor for the development of hepatocellular carcinoma (HCC). However, the role of Type 2 diabetes on the development of HCC in the presence of chronic hepatitis B (CHB) remains inconclusive. We conducted this hospital-based case-control study to evaluate the roles of Type 2 diabetes in HCC development in patients with CHB. From January 2004 to December 2008, a total of 6,275 eligible consecutive patients with chronic hepatitis B virus (HBV) infection were recruited. A total of 1,105 of them were patients with HBV-related HCC and 5,170 patients were CHB but without HCC. We used multivariate logistic regression models to investigate the association between Type 2 diabetes and HCC risk. The prevalence of Type 2 diabetes is higher among HCC patients without cirrhosis than among those with cirrhosis (12.1% vs. 6.7%, p=0.003). Type 2 diabetes was associated with a significantly high risk of HCC in female patients after adjusting for age, family history of HCC, city of residence, hepatitis B e antigen and cirrhosis with an odds ratio (95% confidence interval, CI) of 1.9 (1.1-3.4). Restricted analyses among female patients without cirrhosis indicated that Type 2 diabetes was strongly associated with HCC risk with adjusted odds ratio (95% CI) of 5.6 (2.2-14.1). In conclusion, Type 2 diabetes is independently associated with the increased risk of HCC in female CHB patients. Female CHB patients with Type 2 diabetes are of a high HCC risk population and should be considered for HCC close surveillance program.

Supermarkets are typical crowded public places where the accident caused by evacuation congestion in any emergency event happened easily. In this paper, the number of customers, the ratio of personnel's age, the walking speed and other basic datas were obtained by present observation in a typical supermarket. On this basis, the evacuation scenarios were simulated by buildingEXODUS software for this supermarket and the safety performance was analysed. At last, the safety measures of supermarket management for evacuation were proposed.