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To explore the clinical and genetic characteristics of a Chinese pedigree affected by glycogen storage disease (GSD) type Ia with gout as the first manifestation.Clinical and biochemical data of the pedigree were collected. Available members of the pedigree were subjected to gene sequencing, and the result was analyzed by bioinformatics software. The pedigree was followed up for five years.The proband was a young female manifesting recurrent gout flare, hypoglycemia, and hypertriglyceridemia. One of her younger brothers also presented with dysplasia and hepatic adenoma. Gene sequencing revealed that the proband and her younger brother both harbored c.1022TA (p.I1e341Asn) and c.230+5GA compound heterozygous variants of the G6PC gene , which were inherited from their father and mother, respectively. Among these, the c.230+5GA is an intron region variant which was unreported previously, and bioinformatics analysis showed that it may impact mRNA splicing of the gene. The proband was treated with raw corn starch, allopurinol, and fenofibrate. Gout was well controlled, and she had given birth to a baby girl without GSD.GSD Ia should be considered among young gout patients with hypoglycemia and hepatomegaly, for which gene sequencing is warranted. GSD Ia has a good prognosis after comprehensive treatment with diet and medicine.

Background: Systemic lupus erythematosus (SLE) commonly occurs in premenopausal women and is associated with elevated estrogen levels. Patients with SLE may have abnormal serum triglyceride (TG) levels, and lipid reportedly promotes kidney damage in patients with nephrosis. Since estrogen regulates lipid levels, we investigated the serum lipid levels of premenopausal women with SLE and their relationship with proteinuria. Methods: This cross-sectional study included 123 premenopausal women with SLE (SLE group), who were classified into 24-h urine protein exceeding 0.5 g (24 h-UPRO > 0.5 g, n = 22) and 24 h-UPRO ≤ 0.5 g ( n = 101) subgroups, and 100 similarly aged healthy women (control group). Clinical characteristics and biomarker levels were compared between these groups. The associated factors of proteinuria over 0.5 g/day were evaluated using multivariate logistic regression. A receiver operating characteristic (ROC) curve was plotted to assess the cholesterol (CH) cut-off associated with increased development of proteinuria over 0.5 g/day. Results: The SLE group had significantly higher serum TG levels than that of control group. 24 h-UPRO were significantly correlated with serum creatinine, CH, TG, and uric acid levels. Serum CH level was the greatest associated factor for proteinuria over 0.5 g/day. The area under the ROC curve was 0.843, with a CH cut-off of 4.58 mmol/L. Patients with serum CH above 4.58 mmol/L had a higher proportion of type IV LN, but with no statistical difference. Conclusions: In premenopausal SLE patients, serum TG levels were higher than in healthy women, and serum CH levels were the primary associated factor for proteinuria over 0.5 g/day. Proteinura over 0.5 g/day may occur in women with SLE with serum CH levels >4.58 mmol/L. CH levels may be useful for predicting proteinuria.

The construction of microenvironment-sensitive probes with good cell membrane-targetability can reveal the fundamental properties of cell membranes. Herein, two polarity-sensitive probes, termed

The development of high-performance probes that can visualize and track the dynamic changes of lysosomes is very important for the in-depth study of lysosomes. Herein, we report that a dicyanoisophorone-based probe (named

Oestrogen receptor α (ERα) is overexpressed in two‐thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ERα ‐positive breast cancer can be effectively treated by endocrine therapy, endocrine resistance is an urgent clinical problem. Thus, further understanding of the underlying mechanisms involved in ERα signalling is critical in dealing with endocrine resistance in patients with breast cancer. In the present study, unbiased RNA sequence analysis was conducted between the MCF‐7 and MCF‐7 tamoxifen‐resistant (LCC2) cell lines in order to identify differentially expressed genes. The whole transcriptomic data indicated that the JAK‐STAT pathway is markedly up‐regulated, particularly the ISGF3 complex. As the critical effectors, STAT1 and IRF9 were up‐regulated 5‐ and 20‐fold, respectively, in LCC2 cells. The biological experiments indicated that STAT1 is important for ERα signalling. Depletion of STAT1 or inhibition of STAT1 function significantly decreased levels of ERα protein, ERα ‐target gene expression and cell proliferation in both the MCF‐7 and LCC2 cell lines. Chromatin immunoprecipitation revealed that ERα transcription is associated with STAT1 recruitment to the ERα promoter region, suggesting that transcriptional regulation is one mechanism by which STAT1 regulates ERα mRNA levels and ERα signalling in breast cancer cells. The present study reveals a possible endocrine‐resistant mechanism by which STAT1 modulates ERα signalling and confers tamoxifen resistance. Targeting of STAT1 is a potential treatment strategy for endocrine‐resistant breast cancers.

Stable performance is a technical problem in the completely autotrophic nitrogen removal over nitrite (CANON) process with one single stage, which needs to be addressed. In the current work, a laboratory-scale submerged aerated biological filter (SABF) with a 3-L working volume was introduced into the CANON process to enhance its stable performance for 290 days under the following conditions: temperature of 30 ± 1 °C and dissolved oxygen (DO) level of 0.2–0.8 mg·L−1. The results showed that the average ammonium nitrogen removal efficiencies (ANRE) and total nitrogen removal efficiencies (TNRE) were 97.4% and 75.7%, respectively. A 16S rRNA gene high-throughput sequencing technology confirmed the phyla Proteobacteria and Planctomycetes as the ammonium oxidizing bacteria (AOB) and anaerobic ammonia-oxidizing bacteria (AnAOB) of this CANON process with SABF, respectively. The major contributor to nitrogen removal was the genus Candidatus Brocadia, in Brocadiae. The aim is to present an effective strategy as a reference for the design of full-scale plant for the CANON process.

Dissolved oxygen (DO) is a crucial parameter of the completely autotrophic nitrogen removal over nitrite (CANON) process. This study determined the nitrogen removal performance and microbial community of the CANON process in a laboratory-scale submerged aerated biological filter (SABF) over a DO concentration range from 0 to 1.2 mg·L−1. The results showed that the optimum DO (0.2–0.3 mg·L−1) corresponded to an average ammonium nitrogen removal efficiency of 93.4% and a total nitrogen removal efficiency of 81.0%. A 16S rRNA gene high-throughput sequencing technology confirmed that the phyla Proteobacteria and Nitrospirae enriched, whereas the phylum Planctomycetes was inhibited with increasing DO concentration. At the genus level, the increase of DO concentration resulted in the enrichment of genera Dok59 and Nitrospira, but restrained the genus Candidatus Brocadia. This research can be used to improve the nitrogen removal ability of the CANON process in an SABF in the future.

• Increased expression of CD105 both in the microvascular endothelial cells and stromal cells correlated with malignancy in borderline/malignant phyllodes tumors.

Radix Scutellariae (Scutellaria baicalensis Georgi, RS), a traditional herbal medicine commonly used to treat inflammation, hypertension, cardiovascular disease, bacterial and viral infections, is reported to treat lung cancer by supplements of modern medicine. The total flavonoid aglycones extract (TFAE) from RS is the most important composition for the pharmacodynamic effects. The present study was designed to evaluate the anti-lung tumor effect of TFAE on A549 cells and A549 cell nude mice xenografts. The aim of the study is to investigate the effect and mechanism of TFAE treating non-small cell lung cancer both in vitro and in vivo.The anti-tumor activity of TFAE in vitro was investigated using the MTT assay. The changes of cell invasion and migration were detected by Transwell assay and tube formation experiments were used to detect the anti-angiogenic effect. The anti-tumor effects of TFAE in vivo were evaluated in A549 cell nude mice xenografts. The mechanism of TFAE was detected by flow cytometry technology, western blot assay and immuno-histochemistry assay.In vitro, TFAE inhibited the proliferation, invasion and migration of A549 cells in a dose- and time-dependent manner. In vivo, TFAE by oral administration at 100mg/kg for 30 days decreased the tumor volume and tumor weight in A549 cell xenograft by 25.5% with no statistical significance (P0.05) compared to the cis-platinum positive control group (30.0%). The cell cycle and DNA synthesis experiment illustrated that TFAE could induce A549 cell cycle to arreste in S phase and DNA synthesis in A549 cells be inhibited, while TFAE had no influence on apoptosis of A549 cells. Western Blot assay demonstrated that the treatment of TFAE could make Cyclin D1 decrease and p53 increase both in vitro and in vivo.TFAE displayed the inhibition effects of non-small cell lung cancer both in vitro and in vivo and the underlying mechanism might be related to the increased p53 protein expression and decreased Cyclin D1 expression, leading to cell cycle arrested in S phase and the decrease of DNA synthesis.

Traditional Chinese Medicine (TCM), a complex natural herbal medicine system, has increasingly attracted attention from all over the world. Most research has illustrated the mechanism of TCM based on the active components or single herbs. It was fruitful and effective but far from satisfactory as it failed to gain insights into the interactivity and combined effects of TCM. In this work, we used Bupleurum chinense (B. chinense DC, a species in the genus Bupleurum, family Apiaceae) and Scutellaria baicalensis (S. baicalensis Georgi, a species in the genus Scutellaria, family Lamiaceae), an herbal pair in TCM, to illustrate the combined effect. We compared the diverse effects between the B. chinense-S. baicalensis herbal pair and its compositions in an animal model of Alcoholic Liver Injury to highlight the advantages of the formula. Biochemical and histological indicators revealed that the effect of B. chinense-S. baicalensis was better than its individual parts. Furthermore, metabolite profiling of the serum, liver tissue, and feces were conducted to reveal that the herbal pair largely presented its effects through enhanced tissue penetration to maintain liver-located intervention with less global and symbiotic disturbance. Furthermore, we analyzed the distribution of the metal elements in extracts of the serum and liver tissue and found that the herbal pair significantly regulated the distribution of endogenous selenium in liver tissue. As selenium plays an important role in the anti-oxidative and hepatoprotective effects, it may be the reason for combined effects in BS formula. This research could open new perspectives for exploring the material basis of combined effects in natural herbal medicine.

Ethnopharmacological relevance Scutellariae Radix ( Scutellaria baicalensis Georgi ) is a well-known Traditional Chinese Medicine (TCM) which mainly contains flavonoids. Our previous studies have demonstrated that total aglycone extracts of Scutellaria baicalensis (TAES) can improve kidney disease in rats. Aim of the study To investigate the renal fibrosis (RF) pathogenesis and TAES treatment mechanism in unilateral ureteral obstruction (UUO) rats, using a metabolomics approach based on gas chromatography-mass spectrometry (GC/MS). Methods Rats with RF were divided into 6 groups with rats subjected to sham operation as normal control. The effects of TAES on some RF closely related parameters in UUO rats were investigated. A metabolomics method, based on GC/MS, was developed to monitor metabolic alterations in urine. Multivariate data analysis was utilized to identify biomarkers potentially associated with RF and the anti-RF activity of TAES. Ontology-based enrichment analysis by BiNChE and pathway analysis by MetPA aid in the interpretation of difference metabolites. Results After 10 days of treatment, the parameters of renal function begin returning to normal, and the abnormal high expressions of genes associated with extracellular matrix (ECM) were relived. In the metabolomics study, metabolic perturbations induced by UUO were reversed after treatment and TAES showed a dose-dependent therapy effect on RF, meanwhile, 18 potential biomarkers associated with RF were identified. Enrichment analysis of metabolites shows an over representation of mostly alkane-alpha, omega-diamine and alpha, omega-dicarboxylic acid, and these biomarkers are primarily involved in Glycine, serine and threonine metabolism, Retinol metabolism, Arginine and proline metabolism and Fructose and mannose metabolism. Conclusions Our findings indicate that TAES have positive effects on UUO-induced RF in rats, meanwhile, metabolomics method coupled with metabolites enrichment analysis is a useful tool for revealing the pathogenesis of diseases and action mechanism of TCM on the whole body.

In this work, we reported the synthesis of water-soluble carbon dots (CDs) by a one-step hydrothermal synthetic route using polyamidoamine (PAMAM) as platform and passivant, where the formation of CDs capped with PAMAM and the surface passivation were realized simultaneously. As a result, the prepared PAMAM-CDs were uniform, monodispersed sphere particles with an approximate diameter of about 2 nm, and the fluorescence and electrochemiluminescence (ECL) response of the nanocomposite film were enhanced. By combining the high sensitivity of ECL and the selectivity of immunoreactions, an ECL immunosensor for facile, rapid, and ultrasensitive detecting of ketamine was constructed, and the further application of the immunoassay was investigated. Under optimal experimental conditions, the obtained immunosensor showed a wide linear detection range from 0.2 to 200 ng mL−1 with a detection limit at 0.067 ng mL−1 in 0.1 M phosphate buffer solutions (pH 7.4). The immunosensor was successfully applied to the determination of ketamine in blood plasma. This kind of assay is expected to pave new avenues in label-free drug assays.

A facile and green synthesis was employed to synthesize water-soluble carbon dots that were shown to be uniform monodisperse spheres with an average diameter of approximately 4 nanometers. Because of their strong adsorption, the carbon dots were assembled on a glassy carbon electrode without a bridging agent. The modified electrode was employed for the sensitive determination of dopamine. In 0.1 mole per liter phosphate buffer at pH 6.0, the peak currents of dopamine increased at the modified electrode. A calibration curve for dopamine was obtained from 1.5 × 10−7 to 1.5 × 10−4 mole per liter with a limit of detection of 2.6 × 10−8 mole per liter. The sensor was employed to determine dopamine in human plasma without interferences from uric acid and ascorbic acid. The carbon dot modified electrode also exhibited high stability and excellent precision. The results demonstrate the facile fabrication of a carbon dot-based sensor and a sensitive method for the determination of dopamine.

Chronic renal failure (CRF) is a severe disease that can lead to a decline of life quality. Radix Scutellariae is a well-known traditional Chinese medicine (TCM). Our previous study has demonstrated that the Total Aglycone Extracts of Scutellaria baicalensis (TAES), can improve renal fibrosis induced by mercuric chloride in rats. However, no research has investigated the efficacy and mechanism of TAES in treating CRF. In the present study, we investigated the effects of TAES on some closely related parameters in 5/6 nephrectomy CRF rats, and studied the pathogenesis of CRF and the mechanism of TAES treatment using a metabonomics method based on gas chromatography coupled with mass spectrometry (GC/MS). Rats with CRF were divided into six groups with rats subjected to a sham operation as the normal control. After eight weeks of treatment by TAES, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were decreased, and the metabolic perturbations induced by 5/6 nephrectomy were reversed according to pattern recognition analysis. Meanwhile, 18 potential biomarkers associated with CRF were identified, and the affected metabolic pathways in 5/6 nephrectomy rats were extracted based on the differential metabolites. Our findings suggest that TAES have positive effects on 5/6 nephrectomy-induced CRF in rats and show therapeutic potentials in CRF treatment. Our findings also indicate that metabonomics analysis based on GC/MS is a useful tool for studying the effect of drugs on the whole body, exploring biomarkers involved in CRF and elucidating the potential therapeutic mechanisms of TCM.

Good start-up and performance are essential for the completely autotrophic nitrogen removal over nitrite (CANON) process, and inorganic carbon (IC) is also important for this process. In this study, a lab-scale submerged aerated biological filter (SABF) was adopted for the CANON process. A 16S rRNA gene high-throughput sequencing analysis showed that the phyla Proteobacteria and Planctomycetes were the dominant microorganisms and that the genus Candidatus Brocadia functioned as the nitrogen remover. The effect of IC on the nitrogen removal was analyzed. The results showed that the optimum concentration ratio of IC to nitrogen (IC/N) was 1.2, which produced the highest average ammonium nitrogen removal rate (ANR) and total nitrogen removal rate (TNR) values of 95.5% and 80.3%, respectively. The average AOB and AnAOB activities were 2.45 mg·L−1·h−1 and 3.57 mg·L−1·h−1, respectively. This research could promote the nitrogen removal ability of the CANON process with a SABF in the future.

We report on an effective strategy for the enhancement in the sensitivity of localized surface plasmon resonance (LSPR). It is based on the use of gold-silver core-shell nanorods (Au-Ag-cs-NRs) immobilized on a glass substrate. The nanorods arrange themselves by self-assembly, and the resulting LSPR band of the Au-Ag-cs-NRs becomes sharper and more intense. The sensitivity to refractive index (RI) of the Au-Ag-cs-NRs on the glass support is ~281 nm per RI unit, which is better by about 30 % compared to gold nanorods immobilized on glass substrate. The system was applied to study the streptavidin-biotin affinity system which is widely used in biosciences. It is found that the red-shift of the LSPR peak linearly increases with the concentration of streptavidin in the 95 pM to 1.7 μM concentration range. The detection limit (at an S/N ratio of 3) is at 35 pM. The results reveal the merits of this approach in terms of label-free optical affinity sensing.

An effective strategy for the immobilization of coupled gold nanoparticles (CGNPs) on an indium tin oxide (ITO) glass substrate without using any peculiar binding molecules was investigated by applying a seed-mediated growth method. The effects of preparation conditions, such as immersion time, growth time, and temperature, were examined. The connectivity of gold nanoparticles was analyzed by extinction spectroscopy and scanning electron microscopy. Under optimal experimental conditions, the CGNPs occupy a dominant position on the ITO substrate surface with an aspect ratio of 2.5 ± 0.4. The CGNPs display a transverse and a longitudinal localized surface plasmon resonance (LSPR) band in the extinction spectrum. Taking the advantages of this assembling manner, the resulting CGNP-based LSPR sensor demonstrated rather high stability and refractive index sensitivity. The sensing performance of the sensor was studied using biotin–streptavidin as a model. The wavelength shift in the longitudinal band establishes a good relationship with the streptavidin concentrations. All the results demonstrate the reliability of the CGNP-based LSPR sensor and the feasibility of this assembling strategy.

We report on a novel electrochemiluminescent (ECL) immunoassay for the ultrasensitive determination of morphine by making use of a gold electrode which was modified with a nanocomposite film containing self-assembled polyamidoamine (PAMAM) CdS quantum dots and electrodeposited gold nanoparticles (Au-NPs). The highly uniform and well-dispersed quantum dots were capped with PAMAM dendrimers. Due to the synergistic effect of the modified quantum dots and the electrodeposited Au-NPs, the ECL response is dramatically enhanced. Under optimal experimental conditions, the immunoreaction between morphine and anti-morphine antibody resulted in a decrease of the ECL signal because of steric hindrance. The calibration plot is linear in the morphine concentration range from 0.2 to 180 ng•mL−1, with a detection limit as low as 67 pg•mL−1. The sensor was successfully applied to the determination of morphine in blood plasma. This kind of assay is expected to pave new avenues in label-free drug assays.

Increased attention is being paid to traditional Chinese medicine (TCM) as a complementary and alternative medicine to provide an effective approach for personalized diagnosis and clinical treatment. TMC performs treatment based on differentiation of TCM syndrome (ZHENG), which may identify special phenotypes by symptoms and signs of patients even if they are in different diseases. There has, however, been skepticism and criticism because syndrome classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which lacks objectivity and repeatability. In order to transform syndrome classification into mainstream medicine, we introduce a macro-micro approach that combines symptoms, clinical indicators, and metabolites. The present paper explores the macro-micro biomarkers of dampness-heat syndrome in chronic hepatitis B and nonalcoholic fatty liver patients, which could provide the basis for developing a possible population-screening tool for selecting target individuals and creating an evaluation index for personalized treatment.

Xiao Chai Hu Tang (XCHT), a compound formula originally recorded in an ancient Chinese medical bookShanghanlun, has been used to treat chronic liver diseases for a long period of time in China. Although extensive studies have been demonstrated the efficacy of this formula to treat chronic hepatitis, hepatic fibrosis, and hepatocarcinoma, how it works against these diseases still awaits full understanding. Here, we firstly present an overview arranging from the entire formula to mechanism studies of single herb in XCHT and their active components, from a new perspective of “separation study,” and we tried our best to both detailedly and systematically organize the antihepatocarcinoma effects of it, hoping that the review will facilitate the strive on elucidating how XCHT elicits its antihepatocarcinoma role.

Acupuncture is an efficient therapy method originated in ancient China, the study of which based on ZHENG classification is a systematic research on understanding its complexity. The system perspective is contributed to understand the essence of phenomena, and, as the coming of the system biology era, broader technology platforms such as omics technologies were established for the objective study of traditional chinese medicine (TCM). Omics technologies could dynamically determine molecular components of various levels, which could achieve a systematic understanding of acupuncture by finding out the relationships of various response parts. After reviewing the literature of acupuncture studied by omics approaches, the following points were found. Firstly, with the help of omics approaches, acupuncture was found to be able to treat diseases by regulating the neuroendocrine immune (NEI) network and the change of which could reflect the global effect of acupuncture. Secondly, the global effect of acupuncture could reflect ZHENG information at certain structure and function levels, which might reveal the mechanism of Meridian and Acupoint Specificity. Furthermore, based on comprehensive ZHENG classification, omics researches could help us understand the action characteristics of acupoints and the molecular mechanisms of their synergistic effect.