A gluco-mindful approach to diabetic gastroparesis.

Diabetes gastroparesis is a common manifestation of autonomic neuropathy in persons with long-standing, uncontrolled diabetes. Most discussion about its management revolves around the mitigation of symptoms. Here, we share tips on choosing the right glucose-lowering medication, based upon predominant symptomatology of gastroparesis. We highlight about insulin preparations, and their timing of administration, can be tailored according to need. We also emphasize the need to choose oral glucose lowering drugs with care.

Closing the antimicrobial stewardship gap - a call for LMICs to embrace the global antimicrobial stewardship accreditation scheme.

The escalating challenge of antimicrobial resistance (AMR) poses a considerable concern for global health, particularly impacting low- and middle-income countries (LMICs). This article highlights the critical importance of tackling AMR in LMICs by adopting the Global Antimicrobial Stewardship Accreditation Scheme (GAMSAS). GAMSAS is portrayed as a holistic and sustainable strategy for antimicrobial stewardship, extending beyond accreditation to include educational programs, capacity enhancement, improved surveillance, and support for AMS policy research. While acknowledging the global uptake of the scheme, the article highlights its preliminary phase of adoption in LMICs, particularly in high-AMR burden regions like Sub-Saharan Africa. The piece stresses the imperative for LMICs to integrate GAMSAS, underscoring its significance in optimizing antimicrobial usage and patient health outcomes. It advocates for an all-encompassing approach that leverages international cooperation and sustained financial backing, crucial for the effective deployment and enduring success of antimicrobial stewardship efforts in these key areas.

α-Lactalbumin Peptide Asp-Gln-Trp Ameliorates Hepatic Steatosis and Oxidative Stress in Free Fatty Acids-Treated HepG2 Cells and High-Fat Diet-Induced NAFLD Mice by Activating the PPARα Pathway.

SCOPE: Dietary intervention has emerged as a promising strategy for the management of nonalcoholic fatty liver disease (NAFLD). The aim of this study is to investigate the ameliorative effects of the α-lactalbumin peptide Asp-Gln-Trp (DQW) against NAFLD and the underlying mechanism. METHODS AND RESULTS: The models of lipid metabolism disorders are established both in HepG2 cells and in C57BL/6J mice. The results demonstrate that DQW activates peroxisome proliferator-activated receptor α (PPARα) and subsequently ameliorates lipid deposition and oxidative stress in vitro. Interestingly, GW6471 markedly attenuates the modulatory effects of DQW on the PPARα pathway in HepG2 cells. Moreover, results of in vivo experiments indicate that DQW alleviates body weight gain, dyslipidemia, hepatic steatosis, and oxidative stress in high-fat-diet (HFD)-induced NAFLD mice. At the molecular level, DQW activates PPARα, subsequently enhances fatty acid ß-oxidation, and reduces lipogenesis, thereby ameliorating hepatic steatosis. Meanwhile, DQW may ameliorate liver injury and oxidative stress via activating the PPARα/nuclear-factor erythroid 2 (Nrf2)/heme-oxygenase 1 (HO-1) pathway. CONCLUSION: Those results indicate that α-lactalbumin peptide DQW may be an effective dietary supplement for alleviating NAFLD by alleviating lipid deposition and oxidative stress.

Semi-Permanent Ear (Aguille SP) Needle "Migration" into the External Auditory Canal.

Background: Auricular acupuncture (AA) is commonly used by acupuncturists as stand-alone therapy or as an adjunctive to body acupuncture. AA is considered to be safe, with rare complications. The most commonly reported complications are usually transient and include: pain at insertion; minor bleeding; local tenderness; dizziness; and nausea. No reported cases of an Aiguille Semi-Permanente® (ASP®) needle retained in the external auditory canal (EAC) has been found in the medical literature. Case: As part of a treatment for complex regional pain syndrome, auricular ASP needles were placed. When the patient returned 6 weeks later for continued treatment, he reported feeling slightly dizzy at times and that he had a sensation that something might be in his ear canal. Results: This patient appeared to be in his usual good health with normal vital signs. The external ear had no visible ASP needles. An otoscopic examination revealed a yellow reflection from the base of the tympanic membrane (TM), and a gold ASP needle was identified. It was recovered with a normal saline flush of the canal. The TM and EAC were otherwise normal. Conclusions: In this first report of an ASP needle being "lost" in an EAC, perhaps it may have occurred while the patient slept. The event seems to be rare enough, but acupuncturists should be aware of the possibility, and if patients mention a foreign-body sensation in their ears, hearing unusual sounds, or have persistent discomfort or dizziness, the external auditory canal should be examined.

Peroxiredoxin Asp f3 Is Essential for Aspergillus fumigatus To Overcome Iron Limitation during Infection.

Aspergillus fumigatus is an important fungal pathogen that causes allergic reactions but also life-threatening infections. One of the most abundant A. fumigatus proteins is Asp f3. This peroxiredoxin is a major fungal allergen and known for its role as a virulence factor, vaccine candidate, and scavenger of reactive oxygen species. Based on the hypothesis that Asp f3 protects A. fumigatus against killing by immune cells, we investigated the susceptibility of a conditional aspf3 mutant by employing a novel assay. Surprisingly, Asp f3-depleted hyphae were killed as efficiently as the wild type by human granulocytes. However, we identified an unexpected growth defect of mutants that lack Asp f3 under low-iron conditions, which explains the avirulence of the Δaspf3 deletion mutant in a murine infection model. A. fumigatus encodes two Asp f3 homologues which we named Af3l (Asp f3-like) 1 and Af3l2. Inactivation of Af3l1, but not of Af3l2, exacerbated the growth defect of the conditional aspf3 mutant under iron limitation, which ultimately led to death of the double mutant. Inactivation of the iron acquisition repressor SreA partially compensated for loss of Asp f3 and Af3l1. However, Asp f3 was not required for maintaining iron homeostasis or siderophore biosynthesis. Instead, we show that it compensates for a loss of iron-dependent antioxidant enzymes. Iron supplementation restored the virulence of the Δaspf3 deletion mutant in a murine infection model. Our results unveil the crucial importance of Asp f3 to overcome nutritional immunity and reveal a new biological role of peroxiredoxins in adaptation to iron limitation. IMPORTANCE Asp f3 is one of the most abundant proteins in the pathogenic mold Aspergillus fumigatus. It has an enigmatic multifaceted role as a fungal allergen, virulence factor, reactive oxygen species (ROS) scavenger, and vaccine candidate. Our study provides new insights into the cellular role of this conserved peroxiredoxin. We show that the avirulence of a Δaspf3 mutant in a murine infection model is linked to a low-iron growth defect of this mutant, which we describe for the first time. Our analyses indicated that Asp f3 is not required for maintaining iron homeostasis. Instead, we found that Asp f3 compensates for a loss of iron-dependent antioxidant enzymes. Furthermore, we identified an Asp f3-like protein which is partially functionally redundant with Asp f3. We highlight an unexpected key role of Asp f3 and its partially redundant homologue Af3l1 in overcoming the host's nutritional immunity. In addition, we uncovered a new biological role of peroxiredoxins.

Evaluation of reproductive hormones in Egyptian workers occupationally exposed to di-2-ethylhexyl phthalate (DEHP): a cross-sectional study.

OBJECTIVES: Di-2-ethylhexyl phthalate (DEHP) is ubiquitous, known as an endocrine disruptor. DEHP is a widespread prevalence in general and occupational populations which raised great public concerns due to its potentially harmful health effects on the male reproductive system. We aimed to assess occupational levels of DEHP on gonadotropin and gonadal hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) and evaluate its potential effects on Asp327Asn polymorphisms SHBG gene. METHODS: We measured the levels of DEHP of 90 male workers in one of polyvinyl chloride (PVC) industry plant using enzyme-linked immunosorbent assay. Sex hormones were examined and Asp327Asn polymorphisms SHBG gene were detected by PCR-RFLP in all participants. RESULTS: The workers were divided into low- and high- DEHP exposed groups based on the geometric mean (GM) levels (183.86 U/L) in serum. TT and TT: LH ratio were negatively correlated to DEHP levels (r=-0.213, p=0.038), (r=-0.225, p=0.027), respectively. The linear regression analysis revealed that a 10-fold increase of serum DEHP was found to be associated with 2.07 fold decreased in TT and a 2.26 fold decreased in TT/LH ratio. CONCLUSIONS: Serum testosterone is negatively associated with DEHP exposure in occupational workers.

Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics.

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in in vivo and in vitro models of tissue fibrosis, and we describe the likely mechanisms by which artemisinin compounds appear to inhibit cellular and tissue processes that lead to fibrosis. To consider alternative routes of administration of artemisinin for treatment of internal organ fibrosis, we also discuss the potential for more direct oral delivery of Artemisia plant material to enhance bioavailability and efficacy of artemisinin compared to administration of purified artemisinin drugs at comparable doses. It is our hope that greater understanding of the broad anti-fibrotic effects of artemisinin drugs will enable and promote their use as therapeutics for treatment of fibrotic diseases.

Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers.

Tropomyosin receptor kinase A, B and C (TRKA, TRKB and TRKC), which are well-known members of the cell surface receptor tyrosine kinase (RTK) family, are encoded by the neurotrophic receptor tyrosine kinase 1, 2 and 3 (NTRK1, NTRK2 and NTRK3) genes, respectively. TRKs can regulate cell proliferation, differentiation and even apoptosis through the RAS/MAPKs, PI3K/AKT and PLCγ pathways. Gene fusions involving NTRK act as oncogenic drivers of a broad diversity of adult and pediatric tumors, and TRKs have become promising antitumor targets. Therefore, achieving a comprehensive understanding of TRKs and relevant TRK inhibitors should be urgently pursued for the further development of novel TRK inhibitors for potential clinical applications. This review focuses on summarizing the biological functions of TRKs and NTRK fusion proteins, the development of small-molecule TRK inhibitors with different chemotypes and their activity and selectivity, and the potential therapeutic applications of these inhibitors for future cancer drug discovery efforts.

Artemisinin and artemisinin derivatives as anti-fibrotic therapeutics

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in

Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress.

Introduction: Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury. Objectives: This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs. Methods: A literature search was carried out regarding our topic with the keywords of "atherosclerosis" or "Nrf2/HO-1" or "vascular endothelial cells" or "oxidative stress" or "Herbal medicine" or "natural products" or "natural extracts" or "natural compounds" or "traditional Chinese medicines" based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed. Results: These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies. Conclusion: Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

Development of diagnostic PCR and LAMP markers for MALE STERILITY 1 (MS1) in Cryptomeria japonica D. Don.

OBJECTIVE: Due to the allergic nature of the pollen of Cryptomeria japonica, the most important Japanese forestry conifer, a pollen-free cultivar is preferred. Mutant trees detected in nature have been used to produce a pollen-free cultivar. In order to reduce the time and cost needed for production and breeding, we aimed to develop simple diagnostic molecular markers for mutant alleles of the causative gene MALE STERILITY 1 (MS1) in C. japonica to rapidly identify pollen-free mutants. RESULTS: We developed PCR and LAMP markers to detect mutant alleles and to present experimental options depending on available laboratory equipment. LAMP markers were developed for field stations, where PCR machines are unavailable. The LAMP method only needs heat-blocks or a water bath to perform the isothermal amplification and assay results can be read by the naked eye. Because the causative mutations were deletions, we developed two kinds of PCR markers, amplified length polymorphism (ALP) and allele specific PCR (ASP) markers. These assays can be visualized using capillary or agarose gel electrophoresis.

Asperuloside exhibits a novel anti-leukemic activity by triggering ER stress-regulated apoptosis via targeting GRP78.

Acute myeloid leukemia (AML) is a complicated disease of hematopoietic stem cell disorders. However, its pathogenesis mechanisms and therapeutic treatments still remain vague. Asperuloside (ASP) is an iridoid glycoside found in Herba Paederiae, and is a component from traditional Chinese herbal medicine. ASP has been suggested to have various pharmacological activities, such as anti-tumor and anti-inflammation. In this study, we explored the effects of ASP on apoptosis and endoplasmic reticulum (ER) stress in human leukemia cells and in human primary leukemia blasts. ASP treatments selectively reduced the cell viability of human leukemia cells and primary leukemia blasts in a dose-dependent manner. We also found that ASP induced cell death via promoting the cleavage of Caspase-9, -3 and poly (ADP-ribose) polymerase (PARP), which was along with the loss of mitochondrial membrane potential and Cyto-c release from the mitochondria. In addition, we found that ASP significantly induced ER stress in leukemia cells by improving the protein expression levels of glucose-regulated protein of 78 kDa (GRP78), phosphorylated protein kinase RNA-like ER kinase (PERK), phosphorylated eukaryotic translation initiation factor 2 alpha (eIF2α), C/EBP homologous protein (CHOP), phosphorylated inositol-requiring enzyme 1 (p-IRE1), X-box binding protein 1 (XBP1), activating transcription factor-6 (ATF6) and cleaved Caspase-12. Moreover, ER stress suppression markedly abrogated ASP-induced apoptosis. In addition, GRP78 knockdown significantly diminished ER stress and apoptosis triggered by ASP. Importantly, co-immunoprecipitation (IP) analysis further indicated that ASP regulated the interaction between GRP78 and PERK, subsequently meditating the apoptotic cell death. In vivo leukemia xenografts finally validated ER stress and apoptosis were related to the tumor growth reduction induced by ASP. The overall survival of mice was also improved by ASP treatments, accompanied with the significantly reduced number of white blood cells and elevated red blood cells. Together, our present results showed that ASP exerted anti-leukemic effects at least partially via inducing apoptosis regulated by ER stress, and suggested that ASP might be a novel and effective therapeutic strategy for treating human leukemia.

Changes in growth performance, nutrient digestibility, immune blood profiles, fecal microbial and fecal gas emission of growing pigs in response to zinc aspartic acid chelate.

OBJECTIVE: This study was conducted to investigate the effect of zinc aspartic acid chelate (Zn-ASP) on growth performance, nutrient digestibility, blood profiles, fecal microbial and fecal gas emission in growing pigs. METHODS: A total of 160 crossbred ([Landrace×Yorkshire]×Duroc) growing pigs with an initial body weight (BW) of 25.56±2.22 kg were used in a 6-wk trial. Pigs were randomly allocated into 1 of 4 treatments according to their sex and BW (8 replicates with 2 gilts and 3 barrows per replication pen). Treatments were as follows: i) CON, basal diet, ii) TRT1, CON+0.1% Zn-ASP, iii) TRT2, CON+0.2% Zn-ASP, and iv) TRT3, CON+0.3% Zn-ASP. Pens were assigned in a randomized complete block design to compensate for known position effects in the experimental facility. RESULTS: In the current study, BW, average daily gain, and gain:feed ratio showed significant improvement as dietary Zn-ASP increased (p<0.05) in growing pigs. Apparent total tract digestibility (ATTD) of dry matter was increased linearly (p<0.05) in pigs fed with Zn-ASP diets. A linear effect (p<0.05) was detected for the Zn concentration in blood with the increasing levels of Zn-ASP supplementation. Lactic acid bacteria and coliform bacteria were affected linearly (p<0.05) in pigs fed with Zn-ASP diets. However, no significant differences were observed in the ATTD of nitrogen, energy and Zn. And dietary Zn-ASP supplementation did not affect fecal ammonia, hydrogen sulfide and total mercaptans emissions in growing pigs. CONCLUSION: In conclusion, dietary supplementation with Zn-ASP of diet exerted beneficial effects on the growth performance, nutrient digestibility, blood profiles and fecal microbes in growing pigs.

Computational Simulations Identified Two Candidate Inhibitors of Cdk5/p25 to Abrogate Tau-associated Neurological Disorders.

Deregulation of Cdk5 is a hallmark in neurodegenerative diseases and its complex with p25 forms Cdk5/p25, thereby causes severe neuropathological insults. Cdk5/p25 abnormally phosphorylates tau protein, and induces tau-associated neurofibrillary tangles in neurological disorders. Therefore, the pharmacological inhibition of Cdk5/p25 alleviates tau-associated neurological disorders. Herein, computational simulations probed two candidate inhibitors of Cdk5/p25. Structure-based pharmacophore investigated the essential complementary chemical features of ATP-binding site of Cdk5 in complex with roscovitine. Resultant pharmacophore harbored polar interactions with Cys83 and Asp86 residues and non-polar interactions with Ile10, Phe80, and Lys133 residues of Cdk5. The chemical space of selected pharmacophore was comprised of two hydrogen bond donors, one hydrogen bond acceptor, and three hydrophobic features. Decoy test validation of pharmacophore obtained highest Guner-Henry score (0.88) and enrichment factor score (7.23). The screening of natural product drug-like databases by validated pharmacophore retrieved 1126 compounds as candidate inhibitors of Cdk5/p25. The docking of candidate inhibitors filtered 10 molecules with docking score >80.00 and established polar and non-polar interactions with the ATP-binding site residues of Cdk5/p25. Finally, molecular dynamics simulation and binding free energy analyses identified two candidate inhibitors of Cdk5/p25. During 30 ns simulation, the candidate inhibitors established <3.0 Šroot mean square deviation and stable hydrogen bond interactions with the ATP-binding site residues of Cdk5/p25. The final candidate inhibitors obtained lowest binding free energies of -122.18 kJ/mol and - 117.26 kJ/mol with Cdk5/p25. Overall, we recommend two natural product candidate inhibitors to target the pharmacological inhibition of Cdk5/p25 in tau-associated neurological disorders.

Adaptive smith predictor controller for total intravenous anesthesia automation

Anesthetic agent propofol needs to be administered at an appropriate rate to prevent hypotension and postoperative adverse reactions. To comprehend more suitable anesthetic drug rate during surgery is a crucial aspect. The main objective of this proposal is to design robust automated control system that work effi ciently in most of the patients with smooth BIS and minimum variations of propofol during surgery to avoid adverse post reactions and instability of anesthetic parameters. And also, to design advanced computer control system that improves the health of patient with short recovery time and less clinical expenditures. Unlike existing research work, this system administrates propofol as a hypnotic drug to regulate BIS, with fast bolus infusion in induction phase and slow continuous infusion in maintenance phase of anesthesia. The novelty of the paper lies in possibility to simplify the drug sensitivity-based adaption with infusion delay approach to achieve closedloop control of hypnosis during surgery. Proposed work uses a brain concentration as a feedback signal in place of the BIS signal. Regression model based estimated sensitivity parameters are used for adaption to avoid BIS signal based frequent adaption procedure and large off set error. Adaptive smith predictor with lead–lag fi lter approach is applied on 22 diff erent patients' model identifi ed by actual clinical data. The actual BIS and propofol infusion signals recorded during clinical trials were used to estimate patient's sensitivity parameters EC50 and λ. Simulation results indicate that patient's drug sensitivity parameters based adaptive strategy facilitates optimal controller performance in most of the patients. Results are obtained with proposed scheme having less settling time, BIS oscillations and small off set error leads to adequate depth of anesthesia. A comparison with manual control mode and previously reported system shows that proposed system achieves reduction in the total variations of the propofol dose. Proposed adaptive scheme provides better performance with less oscillation in spite of computation delay, surgical stimulations and patient variability. Proposed scheme also provides improvement in robustness and may be suitable for clinical practices.

ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial.

Acute myeloid leukemia (AML) is a heterogeneous disease with cure rates of only 30-40% in patients <60 years old. Cytogenetic and molecular markers have improved our understanding of the different prognostic entities in AML. FLT3 mutations are present in 30-40% of AML cases, conferring a poor prognosis with reduced survival. AXL activates FLT3, impacting adversely on outcome. Both FLT3 and AXL constitute promising molecular targets. ASP2215 (gilteritinib) is a novel, dual FLT3/AXL inhibitor with promising early phase trial data (NCT02014558). A Phase III randomized multicenter clinical trial, comparing ASP2215 to salvage chemotherapy in relapsed/refractory AML with FLT3-mutations is now open to recruitment (NCT02421939). Trial design and objectives are discussed here.

Invasive Aspergillus terreus morphological transitions and immunoadaptations mediating antifungal resistance.

BACKGROUND AND AIMS: Aspergillus terreus Thom is a pathogen of public health and agricultural importance for its seamless abilities to expand its ecological niche. The aim of this study was holistically to investigate A. terreus morphological and immunoadaptations and their implication in antifungal resistance and proliferation during infection. MATERIALS AND METHODS: In-depth unstructured mining of relevant peer-reviewed literature was performed for A. terreus morphological, immune, resistance, and genetic diversity based on the sequenced calmodulin-like gene. RESULTS: Accessory conidia and phialidic conidia produced by A. terreus confer discrete anti-fungal resistance that ensures survivability during therapies. Interestingly, by producing unique metabolites such as Asp-melanin and terretonin, A. terreus is capable of hijacking macrophages and scavenging iron, respectively. As such, A. terreus has established a rare mechanism to mitigate phagocytosis and swing the interaction dynamics in favor of its proliferation and survival in hosts. CONCLUSION: It is further unraveled that besides A. terreus genetic diversity, morphological, biochemical, and immunologic adaptations associated with conidia germination and discharge of chemical signals during infection enable masking of the host defense as an integral part of its strategy to survive and rapidly colonize hosts.

A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model.

The Janus kinase (JAK) family of tyrosine kinases is associated with various cytokine receptors. JAK1 and JAK3 play particularly important roles in the immune response, and their inhibition is expected to provide targeted immune modulation. Several oral JAK inhibitors have recently been developed for treating autoimmune diseases, including rheumatoid arthritis (RA). Here, we investigated the pharmacological effects of peficitinib (formerly known as ASP015K), a novel, chemically synthesized JAK inhibitor. We found that peficitinib inhibited JAK1 and JAK3 with 50% inhibitory concentrations of 3.9 and 0.7 nM, respectively. Peficitinib also inhibited IL-2-dependent T cell proliferation in vitro and STAT5 phosphorylation in vitro and ex vivo. Furthermore, peficitinib dose-dependently suppressed bone destruction and paw swelling in an adjuvant-induced arthritis model in rats via prophylactic or therapeutic oral dosing regimens. Peficitinib also showed efficacy in the model by continuous intraperitoneal infusion. Area under the concentration versus time curve (AUC) at 50% inhibition of paw swelling via intraperitoneal infusion was similar to exposure levels of AUC at 50% inhibition via oral administration, implying that AUC might be important for determining the therapeutic efficacy of peficitinib. These data suggest that peficitinib has therapeutic potential for the oral treatment of RA.

[Characterization of microbial community in produced water from a petroleum reservoir subjected to alkali-surfactant-polymer ASP flooding]. / ä¸‰å ƒ(碱-表面活性剂-聚合物)复合驱油藏采出水微生物群落特征.

Injection of alkali, surfactant and polymer (ASP) into oil reservoir can substantially increase oil recovery compared with water-flooding strategy. However, the effects of these agents on the microbial diversity and community structure, which is important for water management and corrosion control in oil industry, are hitherto poorly understood. Here, we disclosed the microbial diversity and community structure in the produced water collected from four producing wells of an ASP-flooded oilfield at Daqing, China, using high-throughput sequencing technique. Results showed that the average pH in produced water was as high as 9.65. The microbial diversity varied from well to well, and the Shannon diversity index was between 2.00 to 3.56. The Proteobacteria (85.5%-98.3%), γ-proteobacteria (83.7%-97.8%), and alkaliphilic Nitrincola (51.8%-82.5%) were the most dominant phylogenetic taxa at the phylum, class, and genus levels, respectively. A total of 12 potentially sulfide-producing genera were detected, and the most abundant taxon was Sulfurospirillum (0.4%-7.4%). The microbial community of ASP-flooded petroleum reservoir was distinct, showing an alkaliphilic or alkalitolerant potential; a reduced diversity and more simple structure were observed compared with those of the water-flooded petroleum reservoirs that were previously reported.

Clinical Study on Huoxue Rongluo Particles Combined with Acupuncture at Eight Confluent Acupoints in Treatment of Spastic Cerebral Infarction Paralysis / 中国中医药信息杂志

Objective To observe the clinical efficacy of Huoxue Rongluo Particles combined with acupuncture in the eight confluent points of spastic cerebral infarction paralysis and its effects on Glu and Asp levels of serum. Methods Totally 60 patients were divided into two groups: the experimental group and the control group. Both groups received basic Western medicine treatment, and the experimental group received Huoxue Rongluo Particles additionally, one dose a day for two times orally taken; Acupuncture was on eight confluent acupoint, every two days. 15 d is a treatment course, with 6 courses in total. Clinical spasticity index (CSI) and TCM symptom scores before treatment and the treatment of half month, 1 month, 3 months were observed. The levels of Glu and ASP in serum were detected, and TCM clinical efficacy was observed. Results The CSI score, levels of Glu and Asp in serum and TCM symptom scores of the patients after half-month, one-month, and three-month treatment were lower than those before treatment (P0.05). The TCM symptom scores in experimental group was lower than the control group after half-month, one-month and three-month treatment (P<0.05). The total TCM effective rate was 86.67% (26/30) in experimental group, and 80.00% (24/30) in the control group, with the experimental group better than the control group (P<0.05). Conclusion Huoxue Rongluo Particles combined with acupuncture eight confluence acupoints in the treatment of spastic cerebral infarction paralyzed patients can relieve spasm degree, improve TCM clinical symptoms, which mechanism may be related to reducing serum excitatory neurotransmitters.