Efficacy and safety of inulin supplementation for functional constipation: a systematic review protocol

Introduction Functional constipation (FC) is a common digestive system disease, with an uptrend in morbidity and mortality, resulting in huge social and economic losses. Although the guidelines recommend lifestyle intervention as a first-line treatment, lifestyle intervention is not widely used in clinic. Inulin can be used as the basic material of functional food. Clinical studies have shown that inulin supplementation is associated with increased frequency of bowel movements, but has certain side effects. Therefore, the efficacy and safety of inulin in the treatment of FC need to be further evaluated.Methods and analysis We will search Medline, Web of Science, Embase, China National Knowledge Infrastructure Database, Wanfang Database and China Biomedical Literature Database. We will also search the China Clinical Trial Registry, the Cochrane Central Register of Controlled Trials and related conference summaries. This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RevMan V.5.3.5 will be used for analysis.Ethics and dissemination This systematic review will evaluate the efficacy and safety of inulin supplementation for the treatment of FC. All included data will be obtained from published articles, there is no need for the ethical approval, and it will be published in a peer-reviewed journal. Due to lack of a new systematic review in this field, this study will combine relevant randomised controlled trials to better explore the evidence of inulin supplementation in the treatment of FC and guide clinical practice and clinical research.PROSPERO registration number CRD42020189234

Electrodeposition of Copper Metal from the 1-Ethyl-3-methylimidazolium Fluoride ([EMIM]F)-urea-H2O System Containing Cu2O

In this work, [EMIM]F-urea-H2O system is capable of dissolving Cu2O, and then the metallic copper was electrodeposited from this system at room temperature. The reduction of Cu (I) in this system involves a quasi-reversible and one-step single-electron transfer process. The electrodeposition of copper was performed on a tungsten (W) substrate at −0.67 V (vs. Ag) and 353 K via potentiostatic electrolysis. The electrodeposits were identified as metallic copper, as verified by XRD and EDS. SEM image shows that uniform, polygonal nanoparticles of copper were obtained after the potentiostatic static electrolysis

Fabrication of a Metal Micro Mold by Using Pulse Micro Electroforming

Microfluidic devices have been widely used for biomedical and biochemical applications. Due to its unique characteristics, polymethyl methacrylate (PMMA) show great potential in fabricating microfluidic devices. Hot embossing technology has established itself as a popular method of preparing polymer microfluidic devices in both academia and industry. However, the fabrication of the mold used in hot embossing is time-consuming in general and often impractical for economically efficient prototyping. This paper proposes a modified technology for preparing metal micro molds by using pulse micro electroforming directly on metallic substrate, which could save time and reduce costs. In this method, an additive was used to avoid surface defect on deposited nickel. A chemical etching process was performed on the metallic substrate before the electroforming process in order to improve the bonding strength between the deposited structure and substrate. Finally, with the aim of obtaining a metal micro mold with high surface quality (low surface roughness), an orthogonal experiment was designed and conducted to optimize the electroforming parameters. Additionally, metal micro molds with different structures were well prepared by using the optimized parameters

Peptides Trap the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Fusion Intermediate at Two Sites

Human immunodeficiency virus type 1 (HIV-1) entry into target cells requires folding of two heptad-repeat regions (N-HR and C-HR) of gp41 into a trimer of N-HR and C-HR hairpins, which brings viral and target cell membranes together to facilitate membrane fusion. Peptides corresponding to the N-HR and C-HR of gp41 are potent inhibitors of HIV infection. Here we report new findings on the mechanism of inhibition of a N-HR peptide and compare these data with inhibition by a C-HR peptide. Using intact envelope glycoprotein (Env) under fusogenic conditions, we show that the N-HR peptide preferentially binds receptor-activated Env and that CD4 binding is sufficient for triggering conformational changes that allow the peptide to bind Env, results similar to those seen with the C-HR peptide. However, activation by both CD4 and chemokine receptors further enhances Env binding by both peptides. We also show that a nonconservative mutation in the N-HR of gp41 abolishes C-HR peptide but not N-HR peptide binding to gp41. These results indicate that there are two distinct sites in receptor-activated Env that are potential targets for drug or vaccine development

Electrochemical Discharge Grinding of Metal Matrix Composites Using Shaped Abrasive Tools Formed by Sintered Bronze/diamond

Electrochemical discharge machining (ECDM) is a well-known process for machining of particulate reinforced metal matrix composites (MMCs). However, ECDM process suffers several drawbacks such as the lower material removal rate (MRR), high risks of tool wear rate (TWR) and relatively poor surface quality, etc. This study proposes a kind of electrochemical discharge grinding machining (ECDGM) method which employs a special shaped tool electrode. During the process, not only the can the hybrid action of electrochemical dissolution, spark erosion, and abrasive grinding improve the performance of machining MMCs, but also the special shaped of the tool electrode can be used to discharge the machined debris. And thus a higher machining efficiency and lower TWR can be obtained. The performance of developed process was conducted on machining of SiC particulate reinforced aluminum workpiece. The role of peak curre+nt, pulse duration, duty cycle, rotary speed and abrasive grit size has been investigated on MMR and TWR using the nonabrasive round electrode, abrasive round electrode, and abrasive shaped electrode respectively. The experimental results showed that using the shaped abrasive electrode for machining MMCs can achieve a higher MRR and lower TWR, as compared to the non-abrasive round electrode, abrasive round electrode. Besides, the orthogonal method was employed to analyze the relative importance of the machining parameters on MRR and TWR, it has been observed that MRR is affected by the processing parameters following the order of rotary speed > peak current > duty cycle > pulse duration, and TWR is following the order of peak current > duty cycle > pulse duration > rotary speed

Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury

Abstract Background Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. Methods The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. Results It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological functions after TBI. We further demonstrated that ω-3 PUFA supplementation inhibited HMGB1 nuclear translocation and secretion and decreased expression of HMGB1 in neurons and microglia in the lesioned areas. Moreover, ω-3 PUFA supplementation inhibited microglial activation and the subsequent inflammatory response by regulating HMGB1 and the TLR4/NF-κB signaling pathway. Conclusions The results of this study suggest that microglial activation and the subsequent neuroinflammatory response as well as the related HMGB1/TLR4/NF-κB signaling pathway play essential roles in secondary injury after TBI. Furthermore, ω-3 PUFA supplementation inhibited TBI-induced microglial activation and the subsequent inflammatory response by regulating HMGB1 nuclear translocation and secretion and also HMGB1-mediated activation of the TLR4/NF-κB signaling pathway, leading to neuroprotective effects

Human Immunodeficiency Virus (HIV) gp41 Escape Mutants: Cross-Resistance to Peptide Inhibitors of HIV Fusion and Altered Receptor Activation of gp120

Human immunodeficiency virus (HIV) infects cells by fusing with cellular membranes. Fusion occurs when the envelope glycoprotein (Env) undergoes conformational changes while binding to cellular receptors. Fusogenic changes involve assembly of two heptad repeats in the ectodomain of the gp41 transmembrane subunit to form a six-helix bundle (6HB), consisting of a trimeric N heptad repeat (N-HR) coiled-coil core with three antiparallel C heptad repeats (C-HRs) that pack in the coiled-coil grooves. Peptides corresponding to the N-and C-HRs (N and C peptides, respectively) interfere with formation of the 6HB in a dominant-negative manner and are emerging as a new class of antiretroviral therapeutics for treating HIV infection. We generated an escape mutant virus with resistance to an N peptide and show that early resistance involved two mutations, one each in the N- and C-HRs. The mutations conferred resistance not only to the selecting N peptide but also to C peptides, as well as other types of N-peptide inhibitors. Moreover, the N-HR mutation altered sensitivity to soluble CD4. Biophysical studies suggest that the 6HB with the resistance mutations is more stable than the wild-type 6HB and the 6HB formed by inhibitor binding to either wild-type or mutant C-HR. These findings provide new insights into potential mechanisms of resistance to HIV peptide fusion inhibitors and dominant-negative inhibitors in general. The results are discussed in the context of current models of Env-mediated membrane fusion

Ginseng-containing traditional medicine preparations in combination with fluoropyrimidine-based chemotherapy for advanced gastric cancer: A systematic review and meta-analysis.

BackgroundGinseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC.MethodsEight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers.ResultsA total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p ConclusionIn combination with FBC, G-TMPs can potentially enhance efficacy, reduce ADRs, and improve prognosis for patients with AGC. However, high-quality randomized studies remain warranted.Systematic review registrationPROSPERO Number: CRD42021264938

Subgroup analysis of the DCR.

BackgroundGinseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC.MethodsEight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers.ResultsA total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p + T cells, CD4+ T cells, and natural killer cells, as well as a higher CD4+/CD8+ T-cell ratio. Furthermore, lower levels of CA19-9, CA72-4, and CEA were confirmed in the combination treatment group. In addition, G-TMPs reduced the incidence of ADRs during chemotherapy.ConclusionIn combination with FBC, G-TMPs can potentially enhance efficacy, reduce ADRs, and improve prognosis for patients with AGC. However, high-quality randomized studies remain warranted.Systematic review registrationPROSPERO Number: CRD42021264938.</div

Egger’s test of ORR, DCR and QOL.

BackgroundGinseng-containing traditional medicine preparations (G-TMPs) in combination with fluoropyrimidine-based chemotherapy (FBC) are well-known treatments for advanced gastric cancer (AGC), with a superior efficacy to FBC alone. However, evidence regarding their efficacy remains limited. The purpose of this meta-analysis is to evaluate the efficacy and safety of G-TMPs in combination with FBC for the treatment of AGC.MethodsEight electronic databases were searched for randomized controlled trials (RCTs) using G-TMPs with FBC for the treatment of AGC. The primary outcome included the tumor response, while the secondary outcomes included the quality of life (QoL), proportions of peripheral blood lymphocytes, adverse drug reactions (ADRs), and levels of cancer biomarkers. The quality of evidence for each outcome was assessed using GRADE profilers.ResultsA total of 1,960 participants were involved in the 26 RCTs included. Patients treated with FBC plus G-TMPs had better objective response (risk ratio [RR] = 1.23, 95% confidence interval [CI]: 1.13 to 1.35, p + T cells, CD4+ T cells, and natural killer cells, as well as a higher CD4+/CD8+ T-cell ratio. Furthermore, lower levels of CA19-9, CA72-4, and CEA were confirmed in the combination treatment group. In addition, G-TMPs reduced the incidence of ADRs during chemotherapy.ConclusionIn combination with FBC, G-TMPs can potentially enhance efficacy, reduce ADRs, and improve prognosis for patients with AGC. However, high-quality randomized studies remain warranted.Systematic review registrationPROSPERO Number: CRD42021264938.</div