Dual elastography to discriminate adjacent stages of fibrosis and inflammation in chronic hepatitis B: A prospective multicenter study.

BACKGROUND AND AIMS: To evaluate the diagnostic performance of dual elastography (dual-elasto) in continuous differentiation of liver fibrosis and inflammation in a large prospective cohort of patients with chronic HBV. APPROACH AND RESULTS: Adults with positive HBsAg for at least 6 months were recruited from 12 medical centers. Participants underwent dual-elasto evaluations. Biopsy was performed 3 days after dual-elasto examination. Four logistic regression models were trained and strung together into series models. Decision trees based on the series models were performed to achieve continuous differentiation of liver fibrosis and inflammation. The influence of inflammation on the fibrosis stage was also evaluated. A total of 560 patients were included in the training set and 240 in the validation set. Areas under the receiver operating characteristic curve of the series model were 0.82, 0.86, 0.93, and 0.96 to predict ≥F1, ≥F2, ≥F3, and F4 in the validation set, which were significantly higher than those of serum markers and shear wave elastography (all p < 0.05), except for the ≥ F1 levels ( p = 0.09). The AUCs of the series model were 0.93, 0.86, 0.95, and 0.84 to predict inflammation stages ≥G1, ≥G2, ≥G3, and G4, respectively. Decision trees realized 5 continuous classifications of fibrosis and inflammation. Inflammation could enhance the mild fibrosis stage classification while showing limited influences on severe fibrosis or cirrhosis diagnosis. CONCLUSIONS: Dual-elasto demonstrated high performance in the continuous discrimination of fibrosis and inflammation in patients with HBV and could be used to diagnose mild fibrosis without the influence of inflammation.

CW-NET for multitype cell detection and classification in bone marrow examination and mitotic figure examination.

MOTIVATION: Bone marrow (BM) examination is one of the most important indicators in diagnosing hematologic disorders and is typically performed under the microscope via oil-immersion objective lens with a total 100× objective magnification. On the other hand, mitotic detection and identification is critical not only for accurate cancer diagnosis and grading but also for predicting therapy success and survival. Fully automated BM examination and mitotic figure examination from whole-slide images is highly demanded but challenging and poorly explored. First, the complexity and poor reproducibility of microscopic image examination are due to the cell type diversity, delicate intralineage discrepancy within the multitype cell maturation process, cells overlapping, lipid interference and stain variation. Second, manual annotation on whole-slide images is tedious, laborious and subject to intraobserver variability, which causes the supervised information restricted to limited, easily identifiable and scattered cells annotated by humans. Third, when the training data are sparsely labeled, many unlabeled objects of interest are wrongly defined as background, which severely confuses AI learners. RESULTS: This article presents an efficient and fully automatic CW-Net approach to address the three issues mentioned above and demonstrates its superior performance on both BM examination and mitotic figure examination. The experimental results demonstrate the robustness and generalizability of the proposed CW-Net on a large BM WSI dataset with 16 456 annotated cells of 19 BM cell types and a large-scale WSI dataset for mitotic figure assessment with 262 481 annotated cells of five cell types. AVAILABILITY AND IMPLEMENTATION: An online web-based system of the proposed method has been created for demonstration (see https://youtu.be/MRMR25Mls1A).

Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors / 中华血液学杂志

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Neuron stem cell NLRP6 sustains hippocampal neurogenesis to resist stress-induced depression

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

Characteristics of the left heart structure and function in 86 term neonates with intrauterine growth restriction / 中国当代儿科杂志

OBJECTIVES@#To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR).@*METHODS@#This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups.@*RESULTS@#The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (rs=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (rs=-0.229 and -0.225 respectively; P<0.05).@*CONCLUSIONS@#The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.

Synergistic Effects of Organosilicon and Cu(OH)2 in Controlling Sugarcane Leaf Scald Disease.

Sugarcane leaf scald is a systemic disease caused by Xanthomonas albilineans that limits sugarcane yield and quality. Previous research has shown that exogenous application of copper hydroxide to plants is effective in controlling this disease. However, long-term bactericide use causes serious "3R" problems: resistance, resurgence, and residue. It is therefore urgent to discover new methods for the improvement of bactericide efficiency and efficacy. In the present study, disease index values for leaf scald were measured in sugarcane seedlings over time to determine the effects of different concentrations of copper hydroxide, types of silicon additive, and treatment timing after inoculation with X. albilineans on controlling sugarcane leaf scald disease. Our results show copper hydroxide mixed with organosilicon additive could improve the bactericide efficiency and efficacy and reduce the growth of pathogenic bacteria, even at a reduced concentration in both laboratory and field conditions. This study provides an important practical model for controlling sugarcane leaf scald disease by reducing the concentration of bactericide and increasing its efficacy in sugarcane fields.

Liposome-assisted chemical redox cycling strategy for advanced signal amplification: A proof-of-concept toward sensitive electrochemiluminescence immunoassay.

This work presents a novel signal amplification strategy for electrochemiluminescence (ECL) biosensor based on liposome-assisted chemical redox cycling for in situ formation of Au nanoparticles (Au NPs) on TiO2 nanotubes (TiO2 NTs) electrode. The system was exemplified by ascorbic acid (AA)-loaded liposome, the redox cycling of AA utilizing tris (2-carboxyethyl) phosphine (TCEP) as reductant, and the use of Au nanoclusters (Au NCs)/TiO2 NTs as working electrode to implement the ECL detection of prostate specific antigen (PSA). Specifically, the AA-loaded liposomes were used as tags to label the captured PSA through a sandwich immunoreaction. After the lysate of the liposome was transferred onto the interface of Au NCs/TiO2 NTs in the presence of Au3+ and TECP, the chemical redox cycling was triggered. In the cycling, Au3+ was directly reduced in situ by AA to form Au NPs on Au NCs/TiO2 NTs electrode, whereas the oxidation product of AA was reduced by TCEP to regenerate AA. The large loading capacity of the liposome and chemical redox cycling resulted in the incomplete reduction of the Au NCs to Au NPs on the TiO2 NTs electrode, enhancing the ECL intensity greatly. The multiple signal amplification strategy achieved an ultrasensitive detection for PSA with a detection limit down to 6.7 × 10-15 g mL-1 and a wide linear concentration range from 1.0 × 10-14 to 1.0 × 10-8 g mL-1. It is believed that this work is anticipated to extend the employment of advanced chemical redox cycling reaction in the field of ECL bioassays.

Glutathione-stabilized copper nanoclusters mediated-inner filter effect for sensitive and selective determination of p-nitrophenol and alkaline phosphatase activity.

A simple and highly selective fluorescence biosensor has been exploited for p-nitrophenol (p-NP) and alkaline phosphatase (ALP) activity detection based on the glutathione-stabilized copper nanoclusters (GSH-CuNCs) mediated-inner filter effect (IFE). The GSH-CuNCs were prepared by employing GSH as stabilizer and ascorbic acid (AA) as reductant. The obtained GSH-CuNCs exhibited a strong blue fluorescence emission at 420 nm with an excitation wavelength of 365 nm, which overlapped largely with the absorption spectra of p-nitrophenol (p-NP). Therefore, the luminescence of GSH-CuNCs could be quenched by p-NP through inner filter effect. In addition, ALP catalyzed the substrate p-nitrophenyl phosphate (p-NPP) to form p-nitrophenol (p-NP), which also leading to the fluorescence quenching of GSH-CuNCs. The fluorescent strategy was realized for the sensitive determination of p-NP and ALP activity with the promising limit of detection of 20 nM (for p-NP) and 0.003 mU⋅mL-1 (for ALP). Furthermore, the method could be applied to detect the p-NP content in river water samples and ALP activity in human serum samples.

Lycopene ameliorates insulin resistance and increases muscle capillary density in aging via activation of SIRT1.

Lycopene (Ly) is a kind of hydrocarbon, which belongs to the family of tetraterpene carotene and exists in red fruits and vegetables. The decrease of capillary density and blood flow with age is a significant reason for the increase of mortality and morbidity. Herein, our study aims to explore the effects of Ly (a bioactive food compound) on vascular aging in vitro and in vivo and its potential mechanisms. The cytological results showed that Ly could promote the proliferation of human umbilical vein endothelial cell (HUVECs) and enhance the ability of HUVECs to form capillary-like structures. Furthermore, the expression of SIRT1 in aged HUVECs was up-regulated. In vivo, aging rats showed signs of insulin resistance and blood vessel damage. Additionally, the capillary density and blood flow were reduced during the vascular aging process in both D-gal-induced and naturally aging muscle. However, when Ly was given, these conditions could be reversed. Simultaneously, the contents of ATP, lactic acid and pyruvic acid were determined, and it was found that Ly could promote angiogenesis by increasing the utilization rate of glucose and promoting energy metabolism. Finally, in the insulin resistance cell model, we knocked down the SIRT1 and administrated with Ly, and found that it couldn't restore insulin transdution. In conclusion, all the data in this study demonstrate that Ly could reactivate SIRT1 and improve insulin resistance, which was a reversible cause of vascular aging.

Scutellariae Barbatae Herba Extract Promotes Cycle Arrest of Nasopharyngeal Carcinoma Cells by Inhibiting STAT3/SKP2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Scutellariae Barbatae Herba extract on on the cycle arrest of nasopharyngeal carcinoma cells and the possible mechanism by adding different concentration of Scutellariae Barbatae Herba extract （0.25， 0.5， 1 g·L-1） in the culture medium， taking CNE1 （nasopharyngeal carcinoma cells） as the research object. MethodAfter the treatment of CNE1 by Scutellariae Barbatae Herba extract， cell counting kit-8 （CCK-8） was used to detect cell proliferation， and Giemsa staining was used to detect the clone formation rate. Flow cytometry was used to detect cell cycle distribution， and reverse transcription-polymerase chain reaction （ RT-PCR） assay and Western blot assay were used to detect the relative expression of messenger ribonucleic acid （mRNA） by small interfering RNA （siRNA） or overexpression. ResultAs compared with the blank group， the proliferation and colony formation rate of CNE1 in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.05， P<0.01） in a dose and time-dependent manner， whereas the percentage of cells in the presynthetic phase （G0/G1） increased （P<0.05， P<0.01）. The expression level of S-phase kinase associated protein 2 （SKP2） in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.01） as compared with the blank group. As compared with the Scutellariae Barbatae Herba extract group， the protein levels of p21 and p27 significantly decreased in the overexpressed SKP2+ Scutellariae Barbatae Herba extract group （P<0.01）. As compared with the blank group， the signal activation and the phosphorylation level of signal transducer and activator of transcription 3 （STAT3） of CNE1 in the S. barbata extract group significantly decreased （P<0.05， P<0.01）. ConclusionScutellariae Barbatae Herba extract effectively inhibits the proliferation of CNE1， and the mechanism may be related to its action on the STAT3/SKP2 pathway.

Clinical characteristics and gene analysis of GRIN2B gene related neurological developmental disorders in children / 中华儿科杂志

Objective: To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children. Methods: The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health and analyzed retrospectively. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results: Among 11 children 6 were boys and 5 were girls. Two of them were diagnosed with developmental and epileptic encephalopathy. The ages of seizures onset were 3 months and 9 months, respectively. Seizure types included epileptic spasm, tonic seizures, tonic spasm and focal seizures, and 1 patient also had startle attacks. EEG showed interictal multifocal epileptiform discharges. Both of them were added with more than 2 anti-seizure drugs, which were partially effective but could not control. They had moderate to severe mental and motor retardation. The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy, age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay, 2 cases had moderate and 2 cases had mild delay. Multi-focal epileptiform discharges were observed in 3 cases, no abnormality was found in 3 cases, and the remaining 3 cases did not undergo EEG examination. Ten cases underwent brain magnetic resonance imaging (MRI), 6 cases had nonspecific abnormalities and 4 cases were normal. Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients, 8 cases had missense variants and 1 case had nonsense variant, all of which were de novo and 3 of which were novel. Missense variants were found in 10 patients, among them 6 cases had severe developmental delay, 3 cases had moderate and 1 case had mild developmental delay, but the patient with nonsense variant showed mild developmental delay without epilepsy. Conclusions: The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epiletice episodes are refractory. Most of the patients with missense variants had severe developmental delay.

Scutellariae Barbatae Herba Extract Promotes Cycle Arrest of Nasopharyngeal Carcinoma Cells by Inhibiting STAT3/SKP2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Scutellariae Barbatae Herba extract on on the cycle arrest of nasopharyngeal carcinoma cells and the possible mechanism by adding different concentration of Scutellariae Barbatae Herba extract （0.25， 0.5， 1 g·L-1） in the culture medium， taking CNE1 （nasopharyngeal carcinoma cells） as the research object. MethodAfter the treatment of CNE1 by Scutellariae Barbatae Herba extract， cell counting kit-8 （CCK-8） was used to detect cell proliferation， and Giemsa staining was used to detect the clone formation rate. Flow cytometry was used to detect cell cycle distribution， and reverse transcription-polymerase chain reaction （ RT-PCR） assay and Western blot assay were used to detect the relative expression of messenger ribonucleic acid （mRNA） by small interfering RNA （siRNA） or overexpression. ResultAs compared with the blank group， the proliferation and colony formation rate of CNE1 in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.05， P<0.01） in a dose and time-dependent manner， whereas the percentage of cells in the presynthetic phase （G0/G1） increased （P<0.05， P<0.01）. The expression level of S-phase kinase associated protein 2 （SKP2） in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.01） as compared with the blank group. As compared with the Scutellariae Barbatae Herba extract group， the protein levels of p21 and p27 significantly decreased in the overexpressed SKP2+ Scutellariae Barbatae Herba extract group （P<0.01）. As compared with the blank group， the signal activation and the phosphorylation level of signal transducer and activator of transcription 3 （STAT3） of CNE1 in the S. barbata extract group significantly decreased （P<0.05， P<0.01）. ConclusionScutellariae Barbatae Herba extract effectively inhibits the proliferation of CNE1， and the mechanism may be related to its action on the STAT3/SKP2 pathway.

Research Note: Effect of age on hematological parameter and reference intervals for commercial Lohmann silver layer.

Hematological parameters play a key role in assessing the disease states and physiological status of birds, however the reliable information of hematological reference values for Lohmann silver in the pre- and post-laying periods is limited. Thus, the aim of this study was to research the effect of age on hematological parameters and provide reliable reference intervals for commercial Lohmann silver layer. Blood samples were obtained from 231 laying hens at different ages (5-37 wk) with 4-wk sampling intervals. A total of 12 hematological parameters including leucocytes (WBC, 109/L), red blood cell (RBC,1012/L), hemoglobin (HGB, g/L), hematocrit (HCT,%), mean corpuscular volume (MCV, fL), mean corpuscular hemoglobin (MCH, pg), mean corpuscular hemoglobin concentration (MCHC, g/L), red cell distribution width (RDW,%), platelet count (PLT,109/L), mean platelet volume (MPV, fL), platelet volume distribution width (PDW), plateletcrit (PCT, fL) were determined with a reference value advisor. One-ANOVA and Tukey test were utilized to test for significant differences of each parameter between ages. Our findings showed that these parameters were significantly affected by age, except for HCT in the pre-laying period. And reference intervals for all parameters except MCH, MCHC, MCV, MPV, and PDW in the pre-laying period were higher than that in the post-laying period. The results of this study may serve as indispensable information when diagnosing the health of Lohmann silver layer.

Deep Learning Fast Screening Approach on Cytological Whole Slides for Thyroid Cancer Diagnosis.

Thyroid cancer is the most common cancer in the endocrine system, and papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, accounting for 70 to 80% of all thyroid cancer cases. In clinical practice, visual inspection of cytopathological slides is an essential initial method used by the pathologist to diagnose PTC. Manual visual assessment of the whole slide images is difficult, time consuming, and subjective, with a high inter-observer variability, which can sometimes lead to suboptimal patient management due to false-positive and false-negative. In this study, we present a fully automatic, efficient, and fast deep learning framework for fast screening of papanicolaou-stained thyroid fine needle aspiration (FNA) and ThinPrep (TP) cytological slides. To the authors' best of knowledge, this work is the first study to build an automated deep learning framework for identification of PTC from both FNA and TP slides. The proposed deep learning framework is evaluated on a dataset of 131 WSIs, and the results show that the proposed method achieves an accuracy of 99%, precision of 85%, recall of 94% and F1-score of 87% in segmentation of PTC in FNA slides and an accuracy of 99%, precision of 97%, recall of 98%, F1-score of 98%, and Jaccard-Index of 96% in TP slides. In addition, the proposed method significantly outperforms the two state-of-the-art deep learning methods, i.e., U-Net and SegNet, in terms of accuracy, recall, F1-score, and Jaccard-Index (p<0.001). Furthermore, for run-time analysis, the proposed fast screening method takes 0.4 min to process a WSI and is 7.8 times faster than U-Net and 9.1 times faster than SegNet, respectively.

Silicon enhancement for endorsement of Xanthomonas albilineans infection in sugarcane.

Silicon (Si) is considered to be a plant growth and development regulator element as well as provide the regulatory response against various biotic stressors. However, the potential mechanism of Si enhancement to regulate plant disease resistance remains to be studied. Therefore, the current study evaluated the effects of Si application on the performance of sugarcane against Xanthomonas albilineans (Xa) infection. Si was applied exogenously (0, 3.85 and 7.70 g Si/kg soil) and the results show that plant height, stem circumference and leaf width of siliconized sugarcane have been improved, which effectively reduced the disease index (0.17-0.21) and incidence (58.2%-69.1%) after Xa infection. Lowest values of MDA (348.5 nmol g-1 FW) and H2O2 (3539.4 mmol/L) were observed in 7.70 g Si/kg soil followed by in 3.85 g Si/kg soil (MDA: 392.6 nmol g-1 FW and H2O2: 3134.6 mmol/L) than that of the control. Whereas, PAL enzyme activity (50.8 mmol/L), JA (230.2 mmol/L) and SA (2.7 ug mL-1) contents were significantly higher in 7.70 g Si/kg soil followed by in 3.85 g Si/kg soil (PAL: 46.3 mmol/L, JA: 182.7 mmol/L and SA: 2.4 ug mL-1) as compared to control. The lower MDA, H2O2 level and higher enzymatic activities were associated with the highest expression levels of their metabolic pathway associated genes i.e., ShMAPK1, ShLOX, ShPAL, ShAOS, ShAOC, ShC4H, ShCAT, Sh4CL and ShNPR1 (22.08, 15.56, 10.42, 3.35, 2.54, 2.14, 1.82, 1.67 and 1.22 folds, respectively) in 7.70 g Si/kg soil as compared to other experimental units and control. Overall, the results of current study indicates that siliconized sugarcane more actively regulates disease resistance through modulation of growth and MDA, H2O2, SA and JA associated metabolic pathways.

L-Histidine-DNA interaction: a strategy for the improvement of the fluorescence signal of poly(adenine) DNA-templated gold nanoclusters.

An interesting phenomenon is described that the fluorescence signal of poly(adenine) (A) DNA-templated gold nanoclusters (AuNCs) is greatly improved in the presence of L-histidine by means of L-histidine-DNA interaction. The modified nanoclusters display strong fluorescence emission with excitation/emission maxima at 290/475 nm. The fluorescence quantum yield (QY) is improved from 1.9 to 6.5%. Fluorescence enhancement is mainly ascribed to the L-histidine-DNA interaction leading to conformational changes of the poly(A) DNA template, which offer a better microenvironment to protect AuNCs. The assay enables L-histidine to be determined with good sensitivity and a linear response that covers the 1 to 50 nM L-histidine concentration range with a 0.3 nM limit of detection. The proposed method has been applied to the determination of imidazole-containing drugs in pharmaceutical samples. A turn-on fluorescent method has been designed for the sensitive detection of L-histidine as well as imidazole-containing drugs on the basis of the L-histidine-DNA interaction.

Application of real world study and human use experience in research and development of new traditional Chinese medicine drugs / 中国中药杂志

Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.

Consensus on collaborative ethical review of multi-center clinical trials of new drugs of traditional Chinese medicine (version 1.0) / 中国中药杂志

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.

Data collection, quality and evidence formation for human use experience of traditional Chinese medicine / 中国中药杂志

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.