[Post-marketing reevaluation for potential quality risk and quality control in clinical application of traditional Chinese medicines].

The effective quality control in clinical practices is an effective guarantee for the authenticity and scientificity of the findings. The post-marketing reevaluation for traditional Chinese medicines (TCM) focuses on the efficacy, adverse reaction, combined medication and effective dose of drugs in the market by expanded clinical trials, and requires a larger sample size and a wider range of patients. Therefore, this increases the difficulty of quality control in clinical practices. With the experience in quality control in clinical practices for the post-marketing reevaluation for Kangbingdu oral for cold, researchers in this study reviewed the study purpose, project, scheme design and clinical practice process from an overall point of view, analyzed the study characteristics of the post-marketing reevaluation for TCMs and the quality control risks, designed the quality control contents with quality impacting factors, defined key review contents and summarized the precautions in clinical practices, with the aim to improve the efficiency of quality control of clinical practices. This study can provide reference to clinical units and quality control-related personnel in the post-marketing reevaluation for TCMs.

Serum microRNA 125b as a diagnostic or prognostic biomarker for advanced NSCLC patients receiving cisplatin-based chemotherapy.

AIM: To investigate the expression profile of microRNAs in inoperable advanced non-small cell lung cancer (NSCLC) patients receiving chemotherapy and the potential relevance of microRNAs to clinicopathological characteristics and prognosis. METHODS: Serum samples were taken from 260 inoperable advanced NSCLC patients and 260 healthy individuals. All the patients received cisplatin-based chemotherapy, including NP/NC regimens, GP/GC regimens, and TP/TC regimens. The serum levels of microRNAs (miR-125b, miR-10b, miR-34a and miR-155) were determined by quantitative real-time PCR. RESULTS: Serum levels of the 4 microRNAs examined in NSCLC patients were significantly increased as compared with healthy individuals. The levels of miR-125b and miR-155 were changed in a similar pattern: the patients with stage IV disease had the highest one, while the patients with stage III A and stage III B disease showed similar increased levels. The levels of miR-10b and miR-34a in the patients with different stages were increased to similar extent. The level of miR-125b in poorly differentiated cancer was significantly higher than those in well and moderately differentiated cancers, while the levels of miR-10b, miR-34a, and miR-155 did not significantly differ with cancer differentiation. Among the 4 microRNAs examined, only miR-125b was significantly associated with therapeutic response, exhibiting higher expression levels in non-responsive patients. Furthermore, the high level of miR-125b was significantly correlated with poor patient survival. A multivariate Cox regression analysis showed that the expression level of miR-125b was an independent prognostic marker in NSCLC patients. CONCLUSION: Our results suggest that miR-125b is a potential diagnostic or prognostic biomarker for NSCLC. This finding has important implications for development of targeted therapeutics to overcome chemotherapeutic resistance in NSCLC.

Roles of ten-eleven translocation family proteins and their O-linked ß-N-acetylglucosaminylated forms in cancer development.

Members of the ten-eleven translocation (TET) protein family of which three mammalian TET proteins have been discovered so far, catalyze the sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine which serve an important role in embryonic development and tumor progression. O-GlcNAcylation (O-linked ß-N-acetylglucosaminylation) is a reversible post-translational modification known to serve important roles in tumorigenesis and metastasis especially in hematopoietic malignancies such as myelodysplastic syndromes, chronic myelomonocytic leukemia and acute myeloid leukemia. O-GlcNAcylation activity requires only two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). OGT catalyzes attachment of GlcNAc sugar to serine, threonine and cytosine residues in proteins, while OGA hydrolyzes O-GlcNAc attached to proteins. Numerous recent studies have demonstrated that TETs can be O-GlcNAcylated by OGT, with consequent alteration of TET activity and stability. The present review focuses on the cellular, biological and biochemical functions of TET and its O-GlcNAcylated form and proposes a model of the role of TET/OGT complex in regulation of target proteins during cancer development. In addition, the present review provides directions for future research in this area.

Application of lanthanide-doped upconversion nanoparticles for cancer treatment: a review.

With the excellent ability to transform near-infrared light to localized visible or UV light, thereby achieving deep tissue penetration, lanthanide ion-doped upconversion nanoparticles (UCNP) have emerged as one of the most striking nanoscale materials for more effective and safer cancer treatment. Up to now, UCNPs combined with photosensitive components have been widely used in the delivery of chemotherapy drugs, photodynamic therapy and photothermal therapy. Applications in these directions are reviewed in this article. We also highlight microenvironmental tumor monitoring and precise targeted therapies. Then we briefly summarize some new trends and the existing challenges for UCNPs. We hope this review can provide new ideas for future cancer treatment based on UCNPs.

Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses.

BACKGROUND: Derivation of osteoblast-like cells from human pluripotent stem cells (hPSCs) is a popular topic in bone tissue engineering. Although many improvements have been achieved, the low induction efficiency because of spontaneous differentiation hampers their applications. To solve this problem, a detailed understanding of the osteogenic differentiation process of hPSCs is urgently needed. METHODS: Monolayer cultured human embryonic stem cells and human-induced pluripotent stem cells were differentiated in commonly applied serum-containing osteogenic medium for 35 days. In addition to traditional assays such as cell viability detection, reverse transcription-polymerase chain reaction, immunofluorescence, and alizarin red staining, we also applied studies of cell counting, cell telomerase activity, and flow cytometry as essential indicators to analyse the cell type changes in each week. RESULTS: The population of differentiated cells was quite heterogeneous throughout the 35 days of induction. Then, cell telomerase activity and cell cycle analyses have value in evaluating the cell type and tumourigenicity of the obtained cells. Finally, a dynamic map was made to integrate the analysis of these results during osteogenic differentiation of hPSCs, and the cell types at defined stages were concluded. CONCLUSIONS: Our results lay the foundation to improve the in vitro osteogenic differentiation efficiency of hPSCs by supplementing with functional compounds at the desired stage, and then establishing a stepwise induction system in the future.

[Effect of B4GALT1 on Proliferation of Its Co-cultured Human Acute Myeloid Leukemia Cell Line in Bone Marrow Stromal Cells].

OBJECTIVE: To investigate the effect of bone marrow stromal cell glycosyltransferase B4GALT1 expression on hematopoietic cell proliferation and its upstream regulation mechanism. METHODS: B4GALT1 was overexpressed in human bone marrow stromal cell line HS5, which was then co-cultured with acute myeloid leukemia cell line KG1a. And its effect on hematopoietic cell proliferation was detected by flow cytometry. Dual luciferase reporter assay, real-time PCR and Western blot were used to predict and validate upstream transcription factors that regulate stromal cell B4GALT1 expression. RESULTS: Overexpression of B4GALT1 in HS5 significantly promoted the proliferation of KG1a in the co-culture system. B4GALT1 expression in stromal cells positively correlated with upstream c-Jun expression, which was verified by JNK/c-Jun inhibitors. CONCLUSION: The differential expression of glycosyltransferases and their corresponding glycosylation in the hematopoietic microenvironment play an important role.

[Systematic review and analysis on the appropriate diseases in clinical treatment with Fu's subcutaneous needling therapy].

The clinical research articles relevant with Fu's subcutaneous needling therapy (FSN) were retrieved from CNKI, WANFANG, CBM and PubMed databases till January 2018 since the establishment of database. According to the general international criteria of disease classification, the diseases involved in the articles were classified and summarized. In terms of the clinical application and research of FSN, the questions were extracted and commented through expert's consultation. As a result, 412 articles were included. The statistical results of disease spectrum indicated that FSN was adopted in 65 kinds of diseases in 11 systems. Of these diseases, the relevant somatic pain disorders in the musculoskeletal system were the most appropriate. Professor FU Zhong-hua explained that the clinical physicians of FSN should select the muscle-related disorders as the clinical research subject and treat them with normalized manipulation of FSN. The research on FSN is still at the preliminary stage. It needs more high-quality clinical and basic researches to provide the evidences for the therapeutic effects of FSN.

Interconnecting semiconducting molecules with non-conjugated soft linkers: a way to improve film formation quality without sacrifice in charge mobility.

The formation of high quality homogeneous active component films is essential to the fabrication of many organic optoelectronic devices, especially those having a large area module. However, most small molecule (SM) semiconductors are unable to achieve such a goal via solution processing because their large and rigid π-conjugated structures generally drive them to aggregate or crystallize into inhomogeneous domains in the process. In this work, a SM semiconductor (SM-DPP6T) based on a diketopyrrolopyrrole (DPP) center with three thiophene units on both sides encounters the same problem. However, when its molecules are interconnected with soft alkyl linkers and change into a poly(rod-coil) polymer, PRC-DPP6T, the problem is solved. Compared with SM-DPP6T, PRC-DPP6T can form a high quality homogeneous film with much better uniformity and coverage on silicon wafers by spin-coating. Moreover, the so-prepared PRC-DPP6T field-effect transistors displayed a much narrower performance distribution and comparable mobility when compared with those based on SM-DPP6T (0.17 vs. 0.15 cm2 V-1 s-1). These results demonstrate that the interconnection of SM semiconductor molecules with soft non-conjugated linkers is a promising way to improve film formation quality while keeping mobility intact.

[Characteristics of Organic and Elemental Carbon in PM10 and PM2.5 in Yulin City, Guangxi].

Two hundred eighteen PM10 and 202 PM2.5 samples were collected at three sampling sites to study the pollution characteristics of carbonaceous aerosols in Yulin from July 2015 to March 2016. Organic carbon (OC) and elemental carbon (EC) in the PM10 and PM2.5 samples were analyzed by a Multiwavelength Thermal/Optical Carbon Analyzer, and the characteristics, including pollution levels, temporal and spatial distributions, and possible sources of OC and EC, were investigated. The results showed that the OC and EC mass concentrations in PM10 in Yulin were 10.99 and 5.11 µg·m-3, respectively, while the OC and EC mass concentrations in PM2.5 were 7.51 and 4.70 µg·m-3, respectively. Strong correlations between OC and EC were found in PM10(R2=0.58) and PM2.5(R2=0.60). The winter average concentrations of secondary organic carbon (SOC) in PM10 and PM2.5 were 14.50 µg·m-3 and 6.74 µg·m-3, respectively. The SOC/OC ratios in both the PM10 and PM2.5 were higher than 0.5. The contribution of SOC to OC was 80.6% in PM10 and 77.7% in PM2.5, which were the highest in the summer, in accordance with the high temperature and strong solar radiation in the summer.

[Analysis of Chemical Composition and Pollution Source of the Fine Particulate Matter by the SPAMS in the Four Seasons in Nanning].

To study the chemical composition and pollution sources of the fine particulate matter during the four seasons in Nanning, single particle aerosol mass spectrometry was performed to characterize the fine particulate matter in Nanning during the four seasons. The correlation (R2) between the fine particulate matter number concentration and the mass concentration of the fine particulate matter obtained using SPAMS was all above 0.75 in the observation period. The particle number concentration could reflect the atmospheric pollution situation to some degree. The average mass spectrogram of the fine particulate matter reflected that secondary pollutants were more in winter and spring in Nanning. The Art-2a classification method was used to classify the chemical composition of the fine particulate matter. The results showed that the number concentration of the chemical composition and sources of pollution had differences in the four seasons. Chemical composition could reflect pollution sources. The elevated elemental carbon was positively with increasing coal combustion in winter. The elevated organic carbon was positively correlated with motor vehicle source in autumn. Rich potassium particles, levoglucosan and substance were positively correlated with biomass burning source and dust in summer. The rich sodium particles and heavy metals were higher in spring. During the process of increasing pollution, the contributions of biomass and coal combustion sources were large.

[Physiochemical Properties and Sources of Atmospheric Particulate Matter During Pollution Monitoring in Nanning, China].

Distribution characteristics, chemical constituents, and sources of particulate matter were measured using a scanning mobility particle sizer and single particle aerosol mass spectrometer during pollution monitoring that occurred between December 5th and December 11th, 2016, in Nanning. Results showed that particulate matter (PM) sized between 20 nm-10 µm were concentrated in the 23 to 395 nm range, with a peak of 100 nm. Three new particle types were generated during the course of this monitoring. These new 30 nm particles came into existence between 14:00 to 18:00, and grew to a size of between 40 nm and 110 nm between 20:00 to 06:00 the next day. The generation of the all three new particles was affected by motor vehicle exhaust emissions. Many secondary particles were also produced during this period of pollution. The source of the fine particulate matter was mainly from the burning of biomass, dust, and the combustion of coal. In addition, a long-distance transmission also contributed to the particles from biomass burning.

Polymorphisms in inhibin α gene promoter associated with male infertility.

Inhibins play important roles in normal gonadal function, including regulation of proliferation, differentiation, and steroidogenesis of Leydig and Sertoli cells via paracrine and autocrine processes. In adult males, circulating inhibin levels are correlated with fertility by regulating the number of Sertoli cells, total sperm count, and testicular volume. Given this important role, inhibin-α subunit (INHA) is a strong candidate gene in male fertility. However, limited data regarding the association of polymorphisms of INHA with male fertility are available. This study was based on the hypothesis that polymorphisms in the promoter of INHA are associated with male fertility. Han Chinese patients with non-normozoospermia (n=153) and normozoospermia (n=72) from Northern China were screened, and genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism after INHA promoter was amplified. Statistical analysis results revealed a significant difference in the allele frequency of INHA promoter between males with non-normozoospermia and normozoospermia. For c.-124G>A, males carrying c.-124GG genotype and c.-124GA genotype showed an increased risk of non-normozoospermic syndrome. For c.-16C>T polymorphism, no significant difference in allele frequency was observed between the two groups. Therefore, the haplotype AC possibly displayed a considerable reduced risk of non-normozoospermic syndrome.

Novel triazolyl berberine derivatives prepared via CuAAC click chemistry: synthesis, anticancer activity and structure-activity relationships.

To search for novel anticancer agents, we designed and synthesized a series of new triazolyl berberine derivatives. The evaluation of all the synthesized compounds and their anticancer activities against a panel of four human cancer cell lines including MCF-7 (breast), MCF-7/ADR (breast), SW-1990 (pancreatic), SMMC-7721 (liver) and the noncancer cell line HUVEC (human umbilical vein endothelial cell). The results showed that most of the compounds displayed better anticancer activities against MCF-7 and SMMC-7721 compared with berberine. Among these derivatives, compounds 5p and 5a exhibited the most potent inhibitory activities against the SMMC-7721 and SW-1990 cell lines with IC50 values of 14.861 ± 2.4 µM and 16.798 ± 3.4 µM. Furthermore, compounds 5p, 5a and 5n exhibited much better selectivity toward the normal cell line HUVEC than berberine.

A new class of organic photovoltaic materials: poly(rod-coil) polymers having alternative conjugated and non-conjugated segments.

A new class of organic photovoltaic materials, poly(rod-coil) polymers composed of alternatively definite conjugated and non-conjugated segments, have been proposed. The first five examples based on polyurethane chemistry showed photovoltaic performance surpassing the reference compound, but less dependent on their molecular weight.

[On-site quality control of acupuncture randomized controlled trial: design of content and checklist of quality control based on PICOST].

To effectively guarantee quality of randomized controlld trial (RCT) of acupuncture and develop reasonable content and checklist of on-site quality control, influencing factors on quality of acupuncture RCT are analyzed and scientificity of quality control content and feasibility of on-site manipulation are put into overall consideration. Based on content and checklist of on-site quality control in National 11th Five-Year Plan Project Optimization of Comprehensive Treatment Plan for TCM in Prevention and Treatment of Serious Disease and Clinical Assessment on Generic Technology and Quality Control Research, it is proposed that on-site quality control of acupuncture RCT should be conducted with PICOST (patient, intervention, comparison, out come, site and time) as core, especially on quality control of interveners' skills and outcome assessment of blinding, and checklist of on-site quality control is developed to provide references for undertaking groups of the project.

Novel Triazolyl berberine derivatives prepared via CuAAC click chemistry: Synthesis, Anticancer Activity and Structure-Activity Relationships.

To search for novel anticancer agents, we designed and synthesized a series of new triazolyl berberine derivatives. The evaluation of all the synthesized compounds and their anticancer activities against a panel of four human cancer cell lines including MCF-7 (breast), MCF-7/ADR (breast), SW-1990 (pancreatic), SMMC-7721 (liver) and the non-cancer cell line HUVEC (human umbilical vein endothelial cell). The results showed that most of the compounds displayed better anticancer activities against MCF-7 and SMMC-7721 compared with berberine. Among these derivatives, compounds 5p and 5a exhibited the most potent inhibitory activities against the SMMC-7721 and SW-1990 cell lines with IC50 values of 14.861 ± 2.4 µM and 16.798 ± 3.4 µM. Furthermore, compounds 5p, 5a and 5n exhibited much better selectivity toward the normal cell line HUVEC than berberine.