Search

In the future, suicide risk prediction and management should be transformed from psychiatrist’s judgment (mental illness-like symptoms) into modern technique-guided diagnostics and target drug therapeutics in larger clinical settings. To embrace modern scientific and technological advances, a number of unique diagnostic and therapeutic approaches must be established. This Article provides some important ideas and mechanisms proposed by translational programs.

BACKGROUND In general, atlantoaxial dislocation is rare due to the stability of the C1-C2 complex. Traumatic atlantoaxial dislocations are usually anterior and accompanied by odontoid fractures. Posterior atlantoaxial dislocations are rare, and complete posterior dislocation without associated fracture is even more rare. A case of early recurrence of posterior atlantoaxial dislocation without fracture being in therapy of first closed reduction and then open reduction has not been previously reported. CASE SUMMARY A 45-year-old female presented with traumatic posterior atlantoaxial dislocation (TPAD) of C1-C2 without associated fractures, and Frankel Grade B spinal cord function. She was successfully managed by immediate closed reduction under skull traction. Unexpectedly, 17 d later, re-dislocation was discovered. On day 28, closed reduction was performed as before but failed. Then, open reduction and posterior internal fixation with autologous iliac bone grafts was performed. By 6 mo after surgery, atlantoaxial joint fusion was achieved, and neurological function had recovered to Frankel Grade E. At 12 mo follow-up, she had lost only 15° of cervical rotation, and atlantoaxial complex instability in joint flexing and extending were no longer observed under fluoroscopy. CONCLUSION Early assessment of transverse ligament is critical for TPAD without fracture avoiding re-dislocation after closed reduction.

Cancer treatments become more effective now. One cause of these therapeutic promotions is based on drug selective paradigms in the clinic. A small range of drug selective paradigms (pharmacogenomics, precision-oncology, biomarkers and drug sensitivity testing) have been widely used worldwide. To accelerate the performance of these drug selective strategies, improved understanding of different mechanisms may be useful. Among these four classes of selective systems, drug sensitivity testing (DST) plays a unique role in clinical trials. Biomedical advances of knowledge and technology in current drug selective systems are increasingly importance. In the past two decades, knowledge gap between pathology and therapeutics is gradually filling, especially among different predictive mechanisms. The different drug selective systems are competitive, progress and advantageous in different clinical situations. To face with this diversity of drug selective strategies, guiding principle and technical feasibility need to emphasize. As a powerful platform, DST have some unique characters—high-quality quantification and comparison of responses among anticancer drug of interests. The smooth progress of DST platform depends on increasingly understanding of cancer biology, pathology and pharmacology—including medical knowledge (cancer heterogeneity, plasticity, stem cells and metastasis) and technical versatility (micro-fluidity and apoptotic evaluation). The medical and technical insights into various and uniqueness of DST are especially highlighted in this article.

BACKGROUND Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing. AIM To investigate the role of SIRT1 in intestinal epithelial cells (IECs) in UC and further explore the underlying mechanisms. METHODS We developed a coculture model using macrophages and Caco-2 cells. After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide (NAM), the expression of occludin and zona occludens 1 (ZO-1) was assessed by Western blot analysis. Annexin V-APC/7-AAD assays were performed to evaluate Caco-2 apoptosis. Dextran sodium sulfate (DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 d. Transferase-mediated dUTP nick-end labeling (TUNEL) assays were conducted to assess apoptosis in colon tissues. The expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western blot. RESULTS SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis, whereas NAM administration caused the opposite effects. DSS-induced colitis mice treated with SRT1720 had a lower disease activity index (P < 0.01), histological score (P < 0.001), inflammatory cytokine levels (P < 0.01), and apoptotic cell rate (P < 0.01), while exposure to NAM caused the opposite effects. Moreover, SIRT1 activation reduced the expression levels of GRP78, CHOP, cleaved caspase-12, cleaved caspase-9, and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated mice. CONCLUSION SIRT1 activation reduces apoptosis of IECs via the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and caspase-12. SIRT1 activation may be a potential therapeutic strategy for UC.

Chloroethylnitrosoureas (CENUs) are an important family of chemotherapies in clinical treatment of cancers, which exert antitumor activity by inducing the formation of DNA interstrand crosslinks (dG-dC ICLs). However, the drug resistance mediated by O6-alkylguanine-DNA alkyltransferase (AGT) and absence of tumor-targeting ability largely decrease the antitumor efficacy of CENUs. In this study, we synthesized an azobenzene-based hypoxia-activated combi-nitrosourea prodrug, AzoBGNU, and evaluated its hypoxic selectivity and antitumor activity. The prodrug was composed of a CENU pharmacophore and an O6-benzylguanine (O6-BG) analog moiety masked by a N,N-dimethyl-4-(phenyldiazenyl)aniline segment as a hypoxia-activated trigger, which was designed to be selectively reduced via azo bond break in hypoxic tumor microenvironment, accompanied with releasing of an O6-BG analog to inhibit AGT and a chloroethylating agent to induce dG-dC ICLs. AzoBGNU exhibited significantly increased cytotoxicity and apoptosis-inducing ability toward DU145 cells under hypoxia compared with normoxia, indicating the hypoxia-responsiveness as expected. Predominant higher cytotoxicity was observed in the cells treated by AzoBGNU than those by traditional CENU chemotherapy ACNU and its combination with O6-BG. The levels of dG-dC ICLs in DU145 cells induced by AzoBGNU was remarkably enhanced under hypoxia, which was approximately 6-fold higher than those in the AzoBGNU-treated groups under normoxia and those in the ACNU-treated groups. The results demonstrated that azobenzene-based combi-nitrosourea prodrug possessed desirable tumor-hypoxia targeting ability and eliminated chemoresistance compared with the conventional CENUs.

Past clinical evidence suggests that there is partly an association between suicide risk/mortality and mentally health condition. It is an interesting subject for modern diagnostic implication and therapeutic targeting. As a result, neuropathy in brain and relevant treatment (eased by anti-depressive agents or herbs) can be extensively explored. In order to find useful way for cutting off unnecessary suicide-induced human mortality, mental-related genes or molecules study may move forwards suicide risk prediction, prevention, targeting and application. This perspective highlights emerging areas of human suicide and mental healthcare.

Background:. Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. Methods:. From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. Results:. After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P

Extensive studies have been conducted on the use of fibre-reinforced polymer (FRP) as a confining material in hybrid tubular columns for civil construction, where the design of columns is often controlled by the stiffness and/or strength requirements. By contrast, the capacity of sustaining large deformation without losing structural integrity can be critical in some applications such as the standing supports for underground mines. This paper presents the conceptual development of a novel column form with large deformation capacity. The novel column consists of an outer FRP tube, and an infill made of coarse lumps/aggregates, which can be from coal rejects or other waste/recycled materials, as well as calcium sulfoaluminate (CSA)-based cementitious material with high water content. In addition to its large deformation capacity, the new column allows the extensive, direct and easy use of waste materials and eliminates the need for mixing concrete on site or transporting commercial concrete. This paper also presents the results from a series of compression tests on the new columns as well as two similar column forms. These tests demonstrate the very large deformation capacity of the new column and show that an existing stress-strain model for FRP-confined normal concrete can be used to provide reasonable predictions of the behaviour of the confined infill material in the new column. The potential applications of the new column and the needs for future research are also discussed.

The article entitled “Aberrant Sialylation in Cancer Pathology and Metastasis, a Putative Drug Target Candidate”, by Lu D.Y., Lu T.R., Xu B., Varki A., Huang M., Zhu H., Shen Y., Yarla N.S., has been retracted on the request of the co-authors Dr. Ajit Varki, Ming Huang, Hong Zhu and Ying Shen available at: Anticancer Agents Med Chem. 2018; 18(14): 1952-1961. http://www.eurekaselect.com/165282. The Corresponding Author Dr. Da-Yong Lu has included the name of the co-author Dr. Ajit Varki, Dr. Nagendra Yarla, Ming Huang, Hong Zhu and Ying Shen without their consent and the manuscript has been published in the journal Anti-Cancer Agents in Medicinal Chemistry (ACAMC). Kindly see Bentham Science Policy on Article retraction at the link given below: https://benthamscience.com/journals/anti-cancer-agents-in-medicinal-chemistry/editorial-policies/). Submission of a manuscript to the respective journals implies that all authors have read and agreed to the content of the Copyright Letter or the Terms and Conditions. As such this article represents a severe abuse of the scientific publishing system. Bentham Science Publishers takes a very strong view on this matter and apologizes to the readers of the journal for any inconvenience this may cause.

The constant Ebola epidemic outbreaks in Africa arisen in waves of panic worldwide. There is a high mortality rate (30-70%) among the Ebola-infected people in virus- stricken areas. Despite these horrors, the medical capabilities against this deadly viral disease were provided by limited therapeutic agents/options. As a result, several patented agents, biotherapies or prophylactic/therapeutic vaccines need to be reviving into the global markets—including patents of small molecular chemicals, short sequences or oligomers of DNA/RNA, linkages of chemicals with bio-molecules, herbal medicine and so on. In addition, the possible mechanisms of action of these therapeutic options are underway. To promote Ebola biomedical study, the multiple characters of Ebola infections—its origin, pathologic progress, genomic changes, therapeutic context and economic considerations are outlined in this review. Finally, a great difference can be expected after these types of efforts.

Background and aims AIDS (acquired immune deficient syndrome), a deadly human infectious disease is caused by HIV (human immunodeficiency viruses) infection. Patient's mortality was eventually reduced to one-fourth by combined chemotherapy (usually 3 chemical drugs simultaneously) than earlier HIV/AIDS treatments (single drug or vaccine) in the clinic. Results Combined treatments against HIV/AIDS are still incurable for all patients despite a high rate of patient's survival. Basic viral pathological study and advancing drug development systems for curable medications are indispensable nowadays and in the future. Conclusion Up to date, therapeutic trinity (combined therapy) against HIV/AIDS is generally among chemical drugs. In this article, several forms of other therapeutic attempts for effectively curing efforts against HIV/AIDS are proposed-including the development of next generation therapeutic HIV vaccines and schedules, new categories of bio-therapy, different pathways of immune-modulation, herbal medicines in general (allopathic, Ayurveda and traditional Chinese medicines), high quality of physical exercises, and especially therapeutic combinations guided by latest medical discovery and principles (new forms of therapeutic trinity against HIV-induced pathogenesis and human mortality).

Introduction Suicide is still a major event of human mortality worldwide. Yet human suicide prediction, prevention and therapeutic systems at this moment are generally ineffective in the clinic. No diagnostic system is reliable for significantly suicidal prevention and mortality reduction. As a result, human suicide etiopathologic investigation (especially at genetic/molecular levels in the clinical settings) is quite necessary. In order to boost human suicide researches, emerging human suicide diagnostic/treatment study will be transformed from clinical symptom observations into new generations of candidate drug targets and therapeutics. To achieve this goal, associations between suicidal etiopathologic identification, genetic/bioinformatics-based diagnostics and putative drug targets must be exploited than ever before. After all, the interaction and relationships between environmental/ genetic/molecular clues and overall patient's risk prediction (environmental influences and different therapeutic targets/types) should be found out. Conclusion In the future, effective clinical suicide prediction, prevention and therapeutic systems can be established via scientific expeditions and causality discovery.

The techniques and qualities of drug sensitivity testing (DST) for anticancer treatment have grown rapidly in the past two decades worldwide. Much of DST progress came from advanced systems of technical versatility (faster, highly-throughput, highly-sensitive, and smaller in tumor quantity). As the earliest drug selective system, biomedical knowledge and technical advances for DST are mutually supported. More importantly, many pharmacological controversies are resolved by these technical advances. With this technical stride, the clinical landscape of DST entered into a new phase (>500 samples per testing and extremely low quantity of tumor cells). As a forerunner of the drug selection system, DST awaits a new version that can adapt to complicated therapeutic situations and diverse tumor categories in the clinic. By upholding this goal of pathogenic and therapeutic diversity, DST could eventually cure more cancer patients by establishing high-quality drug selection systems. To smoothen DST development, there is a need to increase the understanding of cancer biology, pathology and pharmacology (cancer heterogeneity, plasticity, metastasis and drug resistance) with well-informative parameters before chemotherapy. In this article, medicinal and technical insights into DST are especially highlighted.

Curcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture model of Caco-2 and differentiated THP-1 cells was established. After administration of curcumin (10 μM), Western blot analysis was performed to evaluate the protein levels of tight junction (TJ) proteins zonula occludens- (ZO-) 1 and claudin-1. Annexin V-APC/7-AAD assays and flow cytometry were conducted to assess Caco-2 cell apoptosis. The expression levels of oxidative stress and endoplasmic reticulum stress- (ERS-) related molecules were determined by Western blot analysis. Curcumin administration significantly upregulated ZO-1 and claudin-1 protein levels and reduced Caco-2 cell apoptosis. The protein levels of oxidative stress markers inducible nitric oxide synthase (iNOS) and γH2AX and ERS-induced apoptosis-related molecules C/EBP homologous protein (CHOP) and cleaved caspase-12 were significantly downregulated upon curcumin treatment. Furthermore, curcumin administration greatly blocked the protein kinase-like endoplasmic reticulum kinase- (PERK-) eukaryotic translation initiation factor 2α- (eIF2α-) activating transcription factor 4- (ATF4-) CHOP signaling pathway. Curcumin enhanced intestinal epithelial barrier integrity in the in vitro coculture model by upregulating TJ protein expressions and reducing intestinal epithelial cell apoptosis. The potential mechanisms may be suppression of ERS and subsequent apoptosis.

Renal ischemia-reperfusion (I/R) can induce oxidative stress and injury via the generation of reactive oxygen species (ROS). Renal proximal tubular cells are susceptible to oxidative stress, and the dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways. A recent study showed that the generation of ROS can increase perilipin 2 (Plin2) expression in HepG2 cells. Some evidence has also demonstrated the association between Plin2 expression and renal tumors. However, the underlying mechanism of Plin2 in I/R-induced acute kidney injury (AKI) remains elusive. Here, using a mouse model of I/R-induced AKI, we found that ROS generation was increased and the expression of Plin2 was significantly upregulated. An in vitro study further revealed that the expression of Plin2, and the generation of ROS were significantly upregulated in primary tubular cells treated with hydrogen peroxide. Accordingly, Plin2 knockdown decreased apoptosis in renal proximal tubular epithelial cells treated with hydrogen peroxide, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). Overall, the present study demonstrated that Plin2 is involved in AKI; knockdown of this marker might limit apoptosis via the activation of PPARα. Consequently, the downregulation of Plin2 could be a novel therapeutic strategy for AKI.

Gastric cancer (GC) is a common gastrointestinal malignancy, and cisplatin (DDP) is an important component of chemotherapeutic regimens for GC. However, the application of DDP is limited by its dose‑dependent systemic toxicity. Resveratrol (RES) is a natural polyphenol compound that has chemopreventive and therapeutic effects against various cancers, including GC. However, whether RES can sensitize GC cells to DDP remains unknown. Following RES/DDP combination treatment, cell viability was determined by Cell Counting Kit‑8 and colony‑forming assays, and cell apoptosis and the cell cycle were detected by FITC‑Annexin V/PI staining assay and PI staining assay, respectively, followed by flow cytometry. Moreover, western blotting was performed to evaluate the protein expression levels, and the intracellular free Ca2+ concentration was determined by a Fluo‑4 AM probe after cell cotreatment with RES and DDP. The present results demonstrated that RES/DDP combination treatment significantly inhibited cell viability, promoted cell apoptosis and induced G2/M phase arrest in AGS cells. In addition, it was determined that RES combined with DDP significantly increased the levels of Bax, cleaved poly‑ADP‑ribose polymerase (PARP), glucose‑regulated protein 78 (GRP78), PRKR‑like ER kinase (PERK), p‑eukaryotic translation initiation factor 2α (p‑eIF2α), CCAAT/enhancer binding protein homologous protein (CHOP) and cleaved caspase‑12, whereas Bcl‑2 expression was downregulated following RES/DDP cotreatment. Moreover, RES/DDP cotreatment significantly upregulated phosphorylated cyclin‑dependent kinase 1 (p‑CDK1, Tyr15), p21Waf1/Cip1 and p27Kip1 protein levels and downregulated Cdc25C protein levels. In conclusion, RES and DDP synergistically inhibited the growth of the gastric adenocarcinoma cell line AGS by inducing endoplasmic reticulum stress‑mediated apoptosis and G2/M phase arrest via activation of the PERK/eIF2α/activating transcription factor 4 (ATF4)/CHOP signaling pathway and caspase‑12 and by inactivating the CDK1‑cyclin B1 complex. These results indicated that RES is a promising adjuvant for DDP during GC chemotherapy.

Natural drugs (either processed or unprocessed) exhibit higher therapeutic index against tumor growths, invasion and remote metastasis with critical roles of anti-proliferation, apoptic-induction, suppressive gene modulation, immune stimulation, anti-inflammatory, free-radical scavenging and low-rate of acquired drug-resistance in clinical cancer trials. Due to a broad-range of biological and pharmacologic activities, growing attention has been focused on elucidating mechanisms of action of drugs, clinical therapeutic evaluations and a new generation of drug developments worldwide. Yet, this kind of medicinal chemistry/pharmacological efforts calls for a new generation of drug inventions and validity. Generally speaking, current natural drugs still face many therapeutic challenges. Many limitations of technical capability and fundamental medical knowledge for natural drug developments and clinical applications need to be overcome. Building up cutting-edge natural drug developmental systems is an inevitable way of updating modern medicines and pharmaceutical science. As a result, higher efficient drug screening routines must be established—including new generations of tumor models, bio-agent pharmaceutical innovation, high quality of chemical-biological extracting/modification technology, Chinese herbal medicine knowledge, modern diagnostics and new therapeutic ideas/paradigms in the clinic. This chapter provides a landscape of natural drug developments and clinical utility, especially Chinese medical conventions.

The causality and etio-pathologic risks for patients with Type 2 Diabetes (T2DM) are important areas in modern medicine. Disease complications are largely unpredictable in patients with T2DM. In the future, we welcome therapeutics of both cutting-edge and traditional for anti-diabetic treatments and management with higher efficiency and less cost. Expanding medical knowledge, behavior/life-style notification in healthcare, modern genetic/bioinformatics diagnostic promotion, clinical developments (Traditional Chinese Medicine and personalized medicine) and new drug developments - including candidate drug targets should be implemented in the future. These efforts might be useful avenues for updating anti-diabetic therapeutics globally. This article aims at introducing this information for T2DM treatment boosts.

Micro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (T2DM), but whether intensive glucose control decreases the risk of diabetic cardiovascular complications remains uncertain. Many studies have confirmed that impaired quality and quantity of mesenchymal stem cells (MSCs) plays a pathogenic role in diabetes. Our previous study found that the abundance of circulating MSCs was significantly decreased in patients with T2DM, which was correlated with the progression of diabetic complications. In addition, metformin-induced MSC apoptosis is one of the reasons for the decreased quantity of endogenous or exogenous MSCs during intensive glucose control. However, the role of glucose in metformin-induced MSC apoptosis during intensive glucose control in T2DM remains unknown. In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner. Thus, our results indicate that the poorer clinical benefit of the intensive glucose control strategy may be related to an adverse effect due to metformin-induced MSC apoptosis during intensive glucose control therapy in patients with T2DM.

Background:The prevalence of Type 2 Diabetes Mellitus (T2DM) continues to rise globally. The T2DM prevalence is not only in developing countries, but also in developed countries now. Correspondingly, the therapeutics of T2DM calls for a change (higher efficiency) due to growing number of patients and increasing economic burdens globally. Entering into this millennium, both piecemeal pathways (idea driven) and exponential growth of human genomic study are developing quickly. Genetypic-phenotypic translation, modern diagnostics, pharmacology, drug developments, traditional Chinese medicine, personalized medicine and so on are promising disciplines for this change. The clinical anti-diabetic therapeutics, pathogenesis, drug development pipelines are especially highlighted.Conclusion:In summary, a general landscape and principle of T2DM is provided.

This study evaluated the hypocholesterolemic effects and potential metabolism of single and combined administrations of capsaicinoids and Lactobacillus plantarum SWUN5815 in ovariectomized rats. Forty female Sprague-Dawley rats were divided into 5 treatment groups. One group was sham-operated (with 1 mL/100 g BW physiological saline), and the 4 other groups were double-ovariectomized: OVX-CON (with 1 mL/100 g BW physiological saline), OVX-CAP (with 1 mL/100 g BW physiological saline and fed with food containing 0.08 g/kg capsaicinoids), OVX-L. P. (with 1 mL 2 × 109 cfu/mL/100 g BW L. plantarum SWUN5815), and OVX-CAP + L. P. (with 1 mL 2 × 109 cfu/mL/100 g BW L. plantarum SWUN5815 and fed with food containing 0.08 g/kg capsaicinoids). Rats were sacrificed after 6 weeks of feeding. Results showed that the combination of capsaicinoids and L. plantarum significantly decreased the total cholesterol, triglyceride and low-density lipoprotein cholesterol of plasma, total cholesterol and lipid accumulation of liver in ovariectomized rats without affecting food intake. Bile acid contents in the fecal excrement and small intestines were significantly increased by the combination compared with the individual effects. However, the mRNA levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA R), farnesoid X receptor (FXR), ileum bile acid binding protein (IBABP), and apical sodium-dependent bile acids transporter (ASBT) significantly decreased. Liver X receptor also remarkably increased. Therefore, these genes potentially affect cholesterol metabolism by inhibiting cholesterol synthesis and promoting excretion of bile acid. The protective effects of the combination of capsaicinoids and L. plantarum SWUN5815 on the intestines were significant in ovariectomized rats.

The performance of pre-gas drainage in low permeable seams especially in CO2 abundant coal seams is not satisfactory. Due to the high affinity of coal to CO2, much lead time is needed for gas drainage boreholes to reduce the coal seam gas content below the threshold limit value (TLV), thus meeting the demand of the scheduled mining activities. In this study, simulations of N2 injection enhanced gas drainage were carried out for CO2-rich coal seams. A binary gas migration model was developed to illustrate gas migration in coal seam. The simulation results matched well with the laboratory test results, indicating that this model could be used to investigate the mechanism of N2 flushing coal seam gas. The parameters affecting the flushing performance were then studied using this model, including coal seam permeability, gas diffusion coefficient, N2 injection pressure andin-situ gas content. These results suggest that coal seam permeability and CO2 diffusion coefficient are the key parameters having significant impacts on the drainage performance whilst N2 diffusion coefficient only has negligible effect. A critical parameter theory was developed to describe the correlation between these parameters (especially coal seam permeability and the diffusion coefficient of coal seam gas). Specifically, in low permeable coal seams, permeability was the critical parameter and the effects of other parameters were insignificant. Similarly, if the diffusion coefficient of coal seam gas was very low, it could become a critical parameter.

In this study, BCPS-1, a polysaccharide previously isolated and characterized from Bupleurum chinense was chemically modified to yield two sulfated derivatives, which we designated as S-BCP1-4 and S-BCP1-8. The physicochemical properties of these sulfated derivatives were then determined by high performance liquid chromatography (HPLC), Fourier transform infrared spectrometry (FT-IR), and gas chromatography (GC), and then compared with those of BCPS-1. Furthermore, the antioxidant activities of all three polysaccharides were also evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical assay, superoxide radical assay and hydroxyl radical assay, while their effects against H2O2-induced cellular senescence were determined using senescence-associated β-galactosidase (SA-β-gal) staining, cell cycle assay and immunoblotting in H2O2-induced mouse lung endothelial cells (MLECs). Compared to BCPS-1, S-BCP1-4 and S-BCP1-8 exhibited remarkable antioxidant effect, and in a concentration-dependent manner. They also provided stronger protection against H2O2-induced cellular senescence in MLECs. These results indicated that the sulfate group in the modified B. chinense polysaccharides might play an important role in radical scavenging and resistance to H2O2-induced senescence. These sulfated polysaccharides could be considered as novel pharmaceutical products with potential antioxidant and anti-senescence effects.

Global climate change is anticipated to raise overall temperatures and has the potential to increase future mortality attributable to heat. Urban areas are particularly vulnerable to heat because of high concentrations of susceptible people. As the world's largest developing country, China has experienced noticeable changes in climate, partially evidenced by frequent occurrence of extreme heat in urban areas, which could expose millions of residents to summer heat stress that may result in increased health risk, including mortality. While there is a growing literature on future impacts of extreme temperatures on public health, projecting changes in future health outcomes associated with climate warming remains challenging and underexplored, particularly in developing countries. This is an exploratory study aimed at projecting future heat-related mortality risk in major urban areas in China. We focus on the 51 largest Chinese cities that include about one third of the total population in China, and project the potential changes in heat-related mortality based on 19 different global-scale climate models and three Representative Concentration Pathways (RCPs). City-specific risk estimates for high temperature and all-cause mortality were used to estimate annual heat-related mortality over two future twenty-year time periods. We estimated that for the 20-year period in Mid-21st century (2041-2060) relative to 1970-2000, incidence of excess heat-related mortality in the 51 cities to be approximately 37,800 (95% CI: 31,300-43,500), 31,700 (95% CI: 26,200-36,600) and 25,800 (95% CI: 21,300-29,800) deaths per year under RCP8.5, RCP4.5 and RCP2.6, respectively. Slowing climate change through the most stringent emission control scenario RCP2.6, relative to RCP8.5, was estimated to avoid 12,900 (95% CI: 10,800-14,800) deaths per year in the 51 cities in the 2050s, and 35,100 (95% CI: 29,200-40,100) deaths per year in the 2070s. The highest mortality risk is primarily in cities located in the North, East and Central regions of China. Population adaptation to heat is likely to reduce excess heat mortality, but the extent of adaptation is still unclear. Future heat mortality risk attributable to exposure to elevated warm season temperature is likely to be considerable in China's urban centers, with substantial geographic variations. Climate mitigation and heat risk management are needed to reduce such risk and produce substantial public health benefits.

Seam gas pre-drainage, is widely used as an effective method to control gas and coal outburst in underground coal mines. However, in CO2 abundant low permeable seams, this technology seems to be less efficient due to the CO2 sorption characteristics and the lower safe mining threshold limit for CO2 applied in many outburst risk management plans. This paper presents the experimental investigations of the applicability of nitrogen (N2) injection to improve gas drainage in CO2 rich seams. Core specimens were obtained from Bulli coal seam, Sydney Basin and N2 flood tests were conducted under different permeability conditions (0.3 mD and 0.06 mD). A triaxial permeability test rig equipped with a back pressure regulator was used to conduct the test. The variation of gas composition, gas outlet flow rate, N2 flushing efficiency, and permeability variation were analyzed. In addition, a comparative study between N2 flushing coal seam CO2 and N2-ECBM was conducted and it was observed that CO2 was much more difficult to drain out and with longer time compared with CH4. Based on the test results, a two-stage flushing mechanism was obtained. In the first stage, the original free phase coal seam gas accounted for the large percentage and this stage last for a shorter time. In the second stage, desorption time governed the flushing efficiency and desorbed gas was the primary gas. It took much longer time than the first stage. The final recovery rate in 0.3 mD and 0.06 mD scenarios were 90.5% and 87.7%, and the N2 consumption/CO2 production ratios were 15 and 11.2, respectively. Through these laboratory experiments, we concluded that N2 injection can significantly decrease coal seam CO2 content level and increase gas drainage efficiency.

Highland barley is one of the most important industrial crops in Tibetan plateau. Previous research indicated that highland barley has many medical functions. In this work, the antibacterial abilities of highland barley were investigated. The protein solutions hydrolyzed by trypsin for 4 h exhibited the highest antibacterial activity. An antibacterial peptide, barleycin, was screened and purified by magnetic liposome extraction combining with the protein profiles of reversed-phase high-performance liquid chromatography (RP-HPLC). Structure, characterization and safety evaluation of barleycin were further investigated. Amino acids sequence was determined as Lys-Ile-Ile-Ile-Pro-Pro-Leu-Phe-His by N-sequencing. Circular dichroism spectra indicated the a-helix conformation of barleycin. The activity spectrum included Bacillus subtilis, Staphylcoccus aureus, Listeria innocua and Escherichia coli and the MICs were from 4–16 μg/ml. Safety evaluations with cytotoxicity and hemolytic suggested this antibacterial peptide could be considered as safe at MICs. Finally, mode of action of barleycin on sensitive cells was primarily studied. The results suggested of the damage of cell membrane. This article is protected by copyright. All rights reserved

Carbon dioxide (CO2) enhanced coalbed methane (ECBM) is an effective method to improve methane (CH4) production and this technology has already been used to increase gas production in several field trials worldwide. One major problem is the injection drop in the later period due to permeability decrease caused by coal matrix swelling induced by CO2 injection. In order to quantify the swelling effect, in this work, coal samples were collected from the Bulli coal seam, Sydney Basin and adsorption tests with simultaneous matrix swelling measurement were conducted. The adsorption and swelling characteristics were analyzed by measuring the adsorption mass simultaneously with the strain measurement. Then experiments were conducted to replicate the ECBM process using the indirect gravity method to obtain the swelling strain change with CO2 injection. The results show that the coal adsorption capacity in CO2 is almost two times greater than that in CH4, and nitrogen adsorption is the least among these gases. A Langmuir-like model can be used to describe the strain with the gas pressure and the swelling strain induced by gas adsorption has a linear relationship with gas adsorption quantity. Moreover, swelling strain increase was observed when CO2 was injected into the sample cell and the swelling strain was almost the sum of the strains induced by different gases at corresponding partial gas pressure.

The purpose of this study was to investigate the effect of ultrasound combined with microbbules (SonoVueTM) on the potency of methylprednisolone in attenuating the renal injury induced by adriamycin in rats. Animal model was established by two intravenous injections of 4 mg/kg adriamycin with a 2-week interval in rats. One week later, the adriamycin injected rats were randomly divided into 7 groups, receiving various treatments daily for 2 weeks. Two doses of methylprednisolone (20 or 40 mg/kg) were administrated alone or 20 mg/kg methylprednisolone and 100 µL SonoVueTM microbbules (1–5 × 108 bubbles/mL; mean diameter of bubbles: 2.5 µm) was co-administrated by intravenous injections from the tail vein. The ultrasound was applied at a frequency of 0.8 MHz and a spatial average temporal average intensity of 2.79 W/cm2 for 5 min at a 50% duty cycle (1 s on 1 s off) on the back skin of the anatomic position of the kidney in rats of two groups combined with ultrasound. Renal injury were analyzed using immunohistochemical staining, real-time PCR, light and transmission electron microcopies. The kidney function related biochemical indexes were measured by automatic biochemistry analyzer. The results showed that adriamycin induced a typical renal injury and 40 mg/kg methylprednisolone injection significantly ameliorated the abnormality of key parameters such as proteinuria, renal mRNA and protein expression levels of nephrin, collagens III and IV as well as podocyte impairment, glomerulosclerosis and tubulointerstitial injury indexes. However, a sub-dose of methylprednisolone at 20 mg/kg was ineffective when administered intravenously, but its potency at this dosage was enhanced by co-administration with 100 µL SonoVueTM microbubbles plus ultrasound irradiation. In conclusion, ultrasound combined with microbubbles can significantly increase local renal drug delivery leading to enhanced therapeutic effect of low dose methylprednisolone in ameliorating adriamycin-induced nephropathy in rats.

Background Last two to three decades, this world witnesses a rapid progress of biomarkers and bioinformatics technologies. Cancer bioinformatics is one of such important omics branches for experimental/clinical studies and applications. Methods Same as other biological techniques or systems, bioinformatics techniques will be widely used. But they are presently not omni-potent. Despite great popularity and improvements, cancer bioinformatics has its own limitations and shortcomings at this stage of technical advancements. Results This article will offer a panorama of bioinformatics in cancer researches and clinical therapeutic applications-possible advantages and limitations relating to cancer therapeutics. A lot of beneficial capabilities and outcomes have been described. As a result, a successful new era for cancer bioinformatics is waiting for us if we can adhere on scientific studies of cancer bioinformatics in malignant- origin mining, medical verifications and clinical diagnostic applications. Conclusion Cancer bioinformatics gave a great significance in disease diagnosis and therapeutic predictions. Many creative ideas and future perspectives are highlighted.

In this work, the interaction between camptothecin (CPT) analogs and fat mass and obesity associated (FTO) was investigated using spectroscopy and molecular docking. From the experimental results, it was found that the CPT analogs caused the fluorescence quenching of FTO through a static quenching procedure. The binding constants and thermodynamic parameters at three different temperatures, the number of binding sites were obtained, which suggested that the hydrophobic interaction and electrostatic force played major role in the reaction between CPT analogs and FTO. Results revealed that 10-hydroxycamptothecin was the strongest quencher.

// Feng Yan 1, 2, * , Le Ying 1, 3, * , Xiaofang Li 1, 2 , Bin Qiao 1, 4 , Qiaohong Meng 2 , Liang Yu 5 , Xiangliang Yuan 1 , Shu-Ting Ren 6 , David W. Chan 7 , Liyun Shi 8 , Peihua Ni 1 , Xuefeng Wang 9 , Dakang Xu 1, 2, 10, 11 and Yiqun Hu 1, 9 1 Faculty of Medical Laboratory Science, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China 3 Department of Tea Science, Zhejiang University, Hangzhou, China 4 Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 5 Department of General Surgery, Shanghai Jiao Tong University Affiliated First People’s Hospital, Shanghai, China, 6 Department of Pathology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, China 7 Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China 8 Department of Microbiology and Immunology, Nanjing University of Chinese Medicine, Nanjing, China 9 Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 10 Hudson Institute of Medical Research, Clayton, Victoria, Australia 11 Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia * Feng Yan and Le Ying contributed equally to this work Correspondence to: Yiqun Hu, email: ichunhu@126.com Dakang Xu, email: dakang.xu@monash.edu Keywords: colorectal cancer, ATF3, genes signature, prognosis Received: January 25, 2017 Accepted: March 08, 2017 Published: March 29, 2017 ABSTRACT The identification of novel biomarkers of cancer is important for improved diagnosis and prognosis. With an abundant amount of resources in the publicly available database, such as the Cancer Genome Atlas (TCGA) database, an integrative strategy is used to systematically characterize the aberrant patterns of colorectal cancer (CRC) based on RNA-Seq, chromatin immunoprecipitation sequencing (ChIP-Seq), tissue microarray (TMA), gene profiling and molecular signatures. The expression of the transcription factor ATF3 was elevated in human CRC specimens in a TMA by immunochemistry analysis compared to the adjacent normal tissues. In addition, ATF3 overexpression associated with a regulatory molecular signature, and its functions are related to the pathogenic development of CRC. Furthermore, putative ATF3 regulatory elements were identified within the promoters of ATF3 target genes and were confirmed by ChIP-Seq. Critically, in higher ATF3 expression cell lines (HCT116 and RKO) with CRISPR/Cas9 mediated ATF3 knock out, we are able to show that ATF3 target genes such as CEACAM1, DUSP14, HDC, HLF and ULBP2 , are required for invasion and proliferation, and they are robustly linked with poor prognosis in CRC. Our findings have important implications for CRC tumorigenesis and may be exploited for diagnostic and therapeutic purposes.

Suicide events and episodes are serious human psychiatric disorders affected by a great number of different environmental/economic factors, early trauma/abuse, human bad living habits, human genomic properties and drug intervention decisions. In order to improve antidepressant therapeutics in clinics, the relationships between efficacy and toxicities of antidepressants have to be considered fundamentally. Since the occurrences and risks of suicidal events or episodes come from interplay between insiders (chemical/genomic/bioinformatics factors) and outsiders (economic/social/ previous trauma conditions and so on), new perspectives and scientific studies must be implemented for revealing these interrelated factors step-by-step and updating therapeutics in human beings. New paradigms and clinical strategies -joint-expert groups and clinical practices (a psychiatrist with other field specialists) should be established for individual patients in future. Thus can some improvements in clinical trials be achieved in a long run?

A series of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at the C4-position were synthesized using piperidine and 1-bromo-3-chloropropane as starting materials via eight steps. Final compounds 8a–q and 9a–i were evaluated for their antiproliferative activity against human lung cancer A549, breast adenocarcinoma MCF-7, and colorectal cancer HCT-116 cell lines. The results showed that fourteen of twenty-six final compounds inhibited the proliferation of three cancer cell lines with IC50 values less than 10 μM. When treated with a representative compound 8n, HCT-116 cells were arrested at G0/G1 phase of the cell cycle. This provided a clue to further investigation of the mechanism of action.

Generalized anxiety disorder (GAD) is a significant and common mental illness with a lifetime prevalence of 3.7%. Regardless of the complexity of treatment decisions for GAD, few studies have conducted systematic comparisons of the efficacies of varying interventions. Thus, this study performed a valid network meta-analysis (NMA) of randomized controlled trials (RCTs) to synthesize direct and indirect evidence for alternative interventions for GAD. We searched four major bibliographic databases, the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, and PubMed, for published RCTs of adult patients with a diagnosis of GAD and allowed for all comorbidities. A total of 91 articles (14,812 participants) were identified in the final NMA. The results showed that all pharmacological treatments except for serotonin modulators and second-generation antipsychotics had greater effects than placebo: norepinephrine-dopamine reuptake inhibitors (standardized mean difference (SMD) -1.84, 95% credible interval -3.05 to -0.62), noradrenergic and specific serotonergic antidepressants (-0.91, -1.62 to -0.20), melatonergic receptor agonists (-0.68, -1.15 to -0.21), selective serotonin reuptake inhibitors (SSRIs; -0.67, -0.90 to -0.43), azapirones (-0.58, -1.00 to -0.17), anticonvulsants (-0.56, -0.85 to -0.28), serotonin-norepinephrine reuptake inhibitors (SNRIs; -0.54, -0.79 to -0.30), and benzodiazepines (BZDs; -0.40, -0.65 to -0.15). Most psychological and self-help interventions exerted greater effects than the waitlist group. However, no psychological interventions had greater effects compared with the psychological placebo. Overall, most pharmacological interventions had larger effect sizes than psychological interventions, and most psychological interventions showed larger effect sizes than self-help interventions.

Neuroleptic malignant syndrome (NMS) is rare but one of the most serious adverse effects of antipsychotics. Here, we report a case of risperidone-associated NMS in which a successful rechallenge of risperidone was observed with a positive follow-up. A 47-year-old female with schizophrenia was treated with risperidone 4 mg/d for 8 months in 2009 and was admitted to our hospital in 2015 owing to violent behavior under persecutory delusions. Risperidone 2 mg/d was initiated and increased to 4 mg/d 54 days later. Further, long-acting injectable (LAI) risperidone 25 mg per two weeks was added on hospital day 15. On hospital day 116, NMS occurred and thus we discontinued all antipsychotics including LAI risperidone, then NMS improved. We resumed LAI risperidone 25 mg per two weeks on hospital day 148, thus we waited for 22 days before re-starting the drug treatment. She was discharged on hospital day 371, then switched to LAI paliperidone 150 mg per four weeks 2 months later. At the time of a follow-up 3 years later, NMS had not reoccurred. This case reports on an unusual presentation of NMS in which no hyperthermia was observed. Furthermore, this case indicated that NMS may occur in a dose-dependent manner. In conclusion, this case reported important information for clinicians with regard to antipsychotic drug rechallenges and proper dosing of APs to avoid or reverse NMS.

Background Cardiovascular complications, especially myocardial infarctions (MIs), are the leading mortality cause in diabetic patients. The transplantation of stem cells into damaged hearts has had considerable success as a treatment for MI, although whether antidiabetic drugs affect the therapeutic efficacy of stem cell transplantation is still unknown. This study aims to understand whether and how metformin, one of the first-line drugs used to treat type 2 diabetes mellitus (T2DM), induces mesenchymal stromal cell (MSC) apoptosis and dampens their cardioprotective effect after transplantation into infarcted hearts. Methods A mouse MI model was generated via permanent ligation of the left anterior descending (LAD) coronary artery. MSCs with or without metformin treatment were transplanted after MI in diabetic mice. Echocardiography was used to assess cardiac function and determine cardiac remodeling, and TTC staining was performed to evaluate infarction size. A mouse gavage model was performed to evaluate bone marrow MSCs for flow cytometry assay. Results Metformin dampened MSC therapeutic efficacy, which increased infarct size and restricted functional cardiac recovery. Specifically, metformin induced the activation of AMP-activated protein kinase (AMPK)-mediated apoptosis through the inhibition of S6K1-Bad-Bcl-xL cell survival signaling, resulting in the upregulated expression of apoptosis-associated proteins and increased MSC apoptosis. Accordingly, counteracting AMPK attenuated metformin-induced apoptosis in MSCs and partially restored their cardioprotective effects in diabetic mice with MI. Furthermore, a decrease in peripheral blood MSCs was found in patients with T2DM who had a metformin medication history. Conclusions Our results highlight an unexpected adverse effect of metformin-induced MSC apoptosis through AMPK-mediated mTOR suppression, which is attenuated by an AMPK inhibitor. Moreover, AMPK inhibition may be a novel strategy for enhancing the effectiveness of stem cell therapy after MI in diabetes. Electronic supplementary material The online version of this article (10.1186/s13287-018-1057-0) contains supplementary material, which is available to authorized users.

Many researchers have concluded that the permeability should be measured after the adsorption equilibrium state is reached and in many permeability models, it is normally assumed that pm (pressure in the coal matrix) is equalized with pf (pressure in the fractures). However, when the dynamic balance between pm and pf is broken which exists in most coalbed methane engineering, the differences between the two pressures induced by gas diffusion and matrix shape factor will generate nonuniform matrix swelling which have not been well learned to date, thus influence the permeability evolution. It is of great importance to investigate this issue on account of it will play a more important role in CO2-enhanced coalbed methane and CO2 sequestration engineering as the coal adsorption capacity for CO2 is considerably higher than that for CH4. To achieve this target, a series of novel coal permeability tests and simultaneous strain measurements were conducted using both natural coal and reconstituted coal. In these experiments, the radial strain evolution characteristics and the permeability evolution characteristics as a function of the adsorption equilibrium time and confining pressure were obtained. Based on the experimental results, the effects of the differences between pm and pf on radial strain evolution and coal permeability evolution were discussed, and a new matrix swelling area propagation theory was achieved. In addition, the differences between natural coal and reconstituted coal in terms of their matrix swelling and stress sensitivity properties were obtained.

After long defeats-almost no marked breakthrough in HIV vaccination campaign has been observed during the past two decades, and we still have not lost our faiths for the development of highly effective and low risk HIV vaccines. Many effective vaccines have been discovered and will certainly enter into the markets within the next 5 to 10 years. In order to promote HIV vaccine developments and clinical HIV therapeutic improvements, this perspective addresses the good and bad sides of currently available HIV vaccines, discusses many subjects of medical significance and finally provides up-to-date information in the field of HIV studies, in particular regarding vaccine developments and HIV pathogenesis.

The interactions between human serum albumin (HSA) and 5-epi-taiwaniaquinone G (G2) or its isomeride (G1) was investigated by fluorescence, UV–visible absorption, resonance light scattering, synchronous fluorescence spectroscopy and 3D spectroscopy under mimic physiological conditions in combination with molecular modeling. The results revealed that G1 and G2 caused the fluorescence quenching of HSA by the formation of G1-HSA and G2-HSA complex, respectively. The binding constants and thermodynamic parameters at three different temperatures were obtained. Hydrophobic and electrostatic interactions played a role in the binding process of HSA and G1. Van der Waals force and hydrogen bond interaction played a role in the binding process of HSA and G2. Results showed that G2 was the stronger quencher and the position of methyl influenced the binding process between HSA and G1 (G2).

Several mines operating in the Bulli seam of the Sydney Basin in NSW, Australia are experiencing difficulties in reducing gas content within the available drainage lead time in various sections of the coal deposit. Increased density of drainage boreholes has proven to be ineffective, particularly in sections of the coal seam rich in CO2. Plus with the increasing worldwide concern on green house gas reduction and clean energy utilisation, significant attention is paid to develop a more practical and economical method of enhancing the gas recovery from coal seams. A technology based on N2 injection was proposed to flush the Coal Seam Gas (CSG) out of coal and enhance the gas drainage process. In this study, laboratory tests on CO2 and CH4 gas recovery from coal by N2 injection are described and results show that N2 flushing has a significant impact on the CO2 and CH4 desorption and removal from coal. During the flushing stage, it was found that N2 flushing plays a more effective role in reducing adsorbed CH4 than CO2. Comparatively, during the desorption stage, the study shows gas desorption after N2 flushing plays a more effective role in reducing adsorbed CO2 than CH4.

Ischemia/reperfusion injury (IRI) has lzong been an area of concern and focus of investigations. Erythropoietin (EPO) exhibits multiple protective effects, and selenium is an antioxidant trace element in the body, however, there have been no reports concerning the effects of EPO combined with sodium selenite on IRI. In the present study, a mouse model of renal IRI (RIRI) was pre‑treated with EPO and sodium selenite to determine the most appropriate combination ratio of the two for further investigation. The results revealed that EPO and sodium selenite had synergistic protective effects in RIRI. EPO was identified as the predominant treatment component, with sodium selenite serving as an adjuvant, and combination treatment was markedly more effective, compared with treatment with either drug alone. The optimal ratio of treatment was 10:1 (10 IU EPO: 1 µg sodium selenite). The results indicated that RIRI markedly induced renal injury, as evidenced by elevated levels of blood urea nitrogen (BUN), as well as higher pathological scores, based on hematoxylin and eosin staining. Pre‑treatment with EPO and sodium selenite significantly decreased serum expression levels of BUN and malonaldehyde, and increased the expression levels of superoxide dismutase, glutathione peroxidase and nitric oxide (NO), compared with the model group. Furthermore, co‑treatment with EPO and sodium selenite upregulated the protein expression levels of phosphatidylinositol‑3 kinase (PI3K) in renal tissue samples. Together, the results suggested that co‑administration of EPO and sodium selenite effectively ameliorates IRI‑induced renal injury by reducing oxidative stress and activating the PI3K/NO signaling pathway.

Background: Anxiety disorder places a heavy burden in the clinical treatment of patients of COVID-19. Acupuncture is a recommended treatment of COVID-19 in China, and clinical researches showed the effectiveness of acupuncture. We will conduct this systematic review and meta-analysis to assess the effectiveness and safety of acupuncture for COVID-19. Methods: Electronic databases of Medline, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), Chinese Scientific and Journal Database (VIP), and Wan Fang database (Wanfang) will be searched for randomized controlled trials of acupuncture for anxiety disorder of COVID-19 from inception of the database to August 10, 2020. Two reviewers will screen studies, collect information independently. We will utilize RevMan 5.3 for meta-analysis. Results: We will publish the study result to a peer-reviewed journal. Conclusion: This study will contribute to provide high-quality evidence of acupuncture for anxiety disorder of COVID-19

The performance of pre-gas drainage in low permeable seams especially in CO2 abundant coal seams is not satisfied. Due to the high affinity between coal and CO2, much more time is required for gas drainage work to reduce the coal seam gas content below the threshold limit value, thus impacting the scheduled mining activities. In this study, N2 injection to enhance gas drainage efficiency was investigated in CO2-rich coal seams. Laboratory tests of N2 enhanced gas drainage were carried out under different permeability conditions. A triaxial permeability test rig equipped with a back pressure regulator was used to conduct the test. The variation of gas composition, gas outlet flow rate, N2 flushing efficiency, and permeability variation were analyzed. A binary gas migration model was developed to illustrate gas migration in laboratory scale and this model was imported to COMSOL Multiphysics. The simulation results were matched well with the laboratory results. Based on the test results, a two-stage flushing mechanism was obtained. In the first stage, free phase coal seam gas accounted for the large percentage and this stage last for a shorter time. In the second stage, desorption time governed the flushing efficiency and desorbed gas was the primary gas. Through these laboratory experiments and simulations, we concluded that N2 injection could significantly decrease coal seam CO2 content level and increase gas drainage efficiency.

118 Background: Both protracted irinotecan and anti-angiogenesis therapy have shown promising results in Ewing sarcoma. We did this phase Ib/II trial to first define the proper dose of irinotecan in combination with anlotinib in Ewing sarcoma (phase Ib) and then evaluate efficacy (phase II). Methods: Patients diagnosed with recurrent or refractory Ewing sarcoma were enrolled and sub-classified into cohort A (≥16y) or cohort B ( < 16y). In the dose-defining phase Ib portion, anlotinib was given at a fixed dose of 12mg D1-14 every 21 days, while the de-escalated 3+3 design was used to detect the recommended dose of irinotecan in each cohort from an initial level of 20mg/m2/d dx5x2. Recommended phase 2 dose (RP2D) was defined as the highest dose at which no more than 30% patients experience a DLT in the first two courses. In the next dose-expanding phase II portion, the primary endpoint was objective response rate at 12 weeks (ORR12w). Results: 41 patients were finally enrolled with 29 in cohortA and 12 in cohortB. For cohortA, first 5 patients were treated at initial level in phase Ib portion, two of whom subsequently experienced delayed diarrhea as dose-limiting toxicity (DLT). Additional six patients were then treated at a lower dose of 15mg/m2. Since no more DLT was recorded, it was used as RP2D. 23/24 patients in cohort A phase II were available for response evaluation at 12 weeks, with one complete response (CR), 14 partial response (PR) , 2 stable disease (SD) and 6 progressive disease (PD). ORR12wwas 62.5%. For cohort B, no DLT was noticed in the first six patients treated at the initial level which was used as RP2D later. Finally, 12 patients were included in cohort B. ORR12wwas 83.3% with two CR, 8 PR and two PD. Although effective, cohort B were closed because of slow enrollment. Most common grade 3/4 adverse events were leukopenia (28.5%), neutropenia (24.4%), anemia (8.7%) and diarrhea (3.7%). The genotype of UGT1A1*1 and UGT1A1*28 were not associated with the risk of diarrhea. Conclusions: The combination of irinotecan and anlotinib demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in advanced Ewing sarcoma. Clinical trial information: NCT03416517.