[Overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treatment of intracerebral hemorrhage].

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.

[Systematic review and Meta-analysis on efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.

[Situation analysis of outcome indicators of randomized controlled trials of traditional Chinese medicine in treatment of hypertensive intracerebral hemorrhage in recent three years].

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.

[Systematic review and Meta-analysis of efficacy and safety of acupuncture therapy on hypertensive intracerebral hemorrhage].

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.

Ammonia-Mediated Bromate Inhibition during Ozonation Promotes the Toxicity Due to Organic Byproduct Transformation.

Ammonia (NH4+) and hydrogen peroxide (H2O2) have been widely used to inhibit bromate formation during ozonation. However, organic byproducts can also pose a risk under these conditions. During bromate inhibition, the influence of NH4+ and H2O2 on organic byproducts and their toxicity should be elucidated. Our study found that NH4+ suppressed organic bromine, but might result in increased toxicity. Adding 0.5 mg/L of NH4+-N substantially increased both the formation of cytotoxicity and genotoxicity (DNA double-strand breaks) of organic byproducts from 0.6 to 1.6 mg-phenol/L, and from 0.3 to 0.8 µg-4-NQO/L (0.5 mg/L Br-, 5 mg/L O3). NH4+ decreased bromate, but increased the overall toxicity of the integrated byproducts (organic byproducts and bromate). Organic nitrogen measurements and 15N isotope analysis showed enhanced incorporation of nitrogen into organic matter when NH4+ and Br- coexisted during ozonation. NH4+ decreased the formation of brominated acetonitriles, but enhanced the formation of brominated nitromethanes and brominated acetamides. These brominated nitrogenous byproducts were partially responsible for this increase in toxicity. Different from ammonia, H2O2 could reduce both bromate and the toxicity of organic byproducts. In the presence of 0.5 mg/L Br- and 10 mg/L O3, adding H2O2 (0.5 mM) substantially suppressed bromate, cytotoxicity formation and genotoxicity formation by 88%, 63% and 67%. This study highlights that focusing on bromate control with NH4+ addition might result in higher toxicity. Efforts are needed to effectively control the toxicities of bromate and organic byproducts simultaneously.

[Analysis of outcomes of randomized controlled trial on compound Chinese herbal medicine formulas in treatment of vascular cognitive impairment caused by cerebral small vessel].

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT) of Chinese herbal medicine formula(CHMF) in the treatment of vascular cognitive impairment caused by cerebral small vessel disease(CSVD-VCI), and provide suggestions for future studies in this field. Three English databases, four Chinese databases, and two online registration websites of clinical trials were searched with use of the search strategy established in advance. Relevant RCTs published in recent ten years were screened, and necessary information was extracted to assess the risk of bias and analyze the outcomes of these RCTs. As a result, a total of 10 461 articles were retrieved, of which 8 681 were kept after de-duplication, and 41 RCTs were included after screening, with a generally higher risk of bias. The outcomes of included RCTs were classified into 9 categories, namely, clinical symptom outcomes, neuroimaging outcomes, neuroelectrophysiological outcomes, blood biochemical outcomes, hemorheology outcomes, physical signs, syndrome scores of traditional Chinese medicine(TCM), clinical effective rate, and safety outcomes. Among them, the most frequently reported outcomes of included RCTs were blood biochemical outcomes, and clinical symptom outcomes showed the highest reporting rate. Besides, 9 RCTs reported syndrome scores of TCM as the outcomes and illustrated corresponding evaluation criteria. The analysis showed that the application of RCT outcomes in this field had clinical rationality and limitations, and there were also some deficiencies in the trial design level, namely, no distinction between primary and secondary outcomes, insufficient blind methods, not detailed description of outcomes, disunity of evaluation tools, and despised endpoint outcomes. These limitations and deficiencies were negatively affecting the quality of RCTs of CHMF in the treatment of CSVD-VCI. Therefore, we suggest that future researchers should be well prepared in the top-level design stage, and actively construct the core outcome set of this field, so as to improve the quality of clinical trials.

Antimicrobial Peptide-Conjugated Hierarchical Antifouling Polymer Brushes for Functionalized Catheter Surfaces.

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

Arginine methyltransferase inhibitor 1 exhibits antitumor effects against cervical cancer in vitro and in vivo.

Protein arginine methyltransferase 5 (PRMT5), a type II PRMT, is highly expressed in several types of tumors including cervical cancer. Arginine methyltransferase inhibitor 1 (AMI-1) inhibits solid tumors by targeting PRMT5. However, the effect of AMI-1 on cervical cancer is still unknown. In this study, we provided the first evidence that AMI-1 reduced cervical cancer cell proliferation, colony formation and promoted cell apoptosis in vitro. Suppression of tumorigenicity was also confirmed in vivo. Mechanistic studies revealed that AMI-1 significantly reduced PRMT5 level in cells and mice xenografts model of cervical cancer. These results suggest that AMI-1 inhibits cervical cancer by type II PRMT5.

Identification of genome-wide SNP-SNP interactions associated with important traits in chicken.

BACKGROUND: In addition to additive genetic effects, epistatic interactions can play key roles in the control of phenotypic variation of traits of interest. In the current study, 475 male birds from lean and fat chicken lines were utilized as a resource population to detect significant epistatic effects associated with growth and carcass traits. RESULTS: A total of 421 significant epistatic effects were associated with testis weight (TeW), from which 11 sub-networks (Sub-network1 to Sub-network11) were constructed. In Sub-network1, which was the biggest network, there was an interaction between GGA21 and GGAZ. Three genes on GGA21 (SDHB, PARK7 and VAMP3) and nine genes (AGTPBP1, CAMK4, CDC14B, FANCC, FBP1, GNAQ, PTCH1, ROR2 and STARD4) on GGAZ that might be potentially important candidate genes for testis growth and development were detected based on the annotated gene function. In Sub-network2, there was a SNP on GGA19 that interacted with 8 SNPs located on GGA10. The SNP (Gga_rs15834332) on GGA19 was located between C-C motif chemokine ligand 5 (CCL5) and MIR142. There were 32 Refgenes on GGA10, including TCF12 which is predicted to be a target gene of miR-142-5p. We hypothesize that miR-142-5p and TCF12 may interact with one another to regulate testis growth and development. Two genes (CDH12 and WNT8A) in the same cadherin signaling pathway were implicated as potentially important genes in the control of metatarsus circumference (MeC). There were no significant epistatic effects identified for the other carcass and growth traits, e.g. heart weight (HW), liver weight (LW), spleen weight (SW), muscular and glandular stomach weight (MGSW), carcass weight (CW), body weight (BW1, BW3, BW5, BW7), chest width (ChWi), metatarsus length (MeL). CONCLUSIONS: The results of the current study are helpful to better understand the genetic basis of carcass and growth traits, especially for testis growth and development in broilers.

[Study on differentially expressed proteins of effect of kudiezi injection on cerebral cortexin rats with cerebral ischemic stroke and heat toxin syndrome].

This study is to investigate the modulation of Kudiezi (KDZ) injection on differential protein expression in cerebral cortex of rats with cerebral ischemic stroke and heat toxin syndrome established by intraperitoneal injection of carrageenan and middle cerebral artery occlusion (MCAO) methods. According to random number table rats were divided into three groups: drug group, model group and sham group. The tripheye tetrazolium chloride (TTC) staining and HE staining were used to observe brain tissue injury of rats. After therapeutic intervention with above drug for seventy-two hours, the level of differential protein expression was analyzed by two-dimensional gel electrophoresis (2-DE). The results show that there are differential protein expressions between cerebral ischemic stroke and heat toxin syndrome rats and sham rats. Furthermore, as a Chinese medicine injection with effect of clearing heat, resolving toxin and dredging collaterals, KDZ injection can decrease alleviate morphological changes of cerebral ischemia, regulate the levels of some differential proteins expression.

Antibiotics removal and antimicrobial resistance control by ozone/peroxymonosulfate-biological activated carbon: A novel treatment process.

Biological activated carbon (BAC) is one of the important treatment processes in wastewater and advanced water treatment. However, the BAC process has been reported to have antimicrobial resistance (AMR) risks. In this study, a new BAC-related treatment process was developed to reduce AMR caused by BAC treatment: ozone/peroxymonosulfate-BAC (O3/PMS-BAC). The O3/PMS-BAC showed better treatment performance on the targeted five antibiotics and dissolved organic matter removal than O3-BAC and BAC treatments. The O3/PMS-BAC process had better control over the AMR than the O3-BAC and BAC processes. Specifically, the amount of targeted antibiotic-resistant bacteria in the effluent and biofilm of O3/PMS-BAC was only 0.01-0.03 and 0.11-0.26 times that of the BAC process, respectively. Additionally, the O3/PMS-BAC process removed 1.76 %-62.83 % and 38.14 %-99.27 % more of the targeted ARGs in the effluent and biofilm than the BAC process. The total relative abundance of the targeted 12 ARGs in the O3/PMS-BAC effluent was decreased by 86 % compared to the effluent after BAC treatment. In addition, Proteobacteria and Bacteroidetes were probably the main hosts for transmitting ARGs in this study, and their relative abundance decreased by 9.6 % and 6.0 % in the effluent of the O3/PMS-BAC treatment compared to that in BAC treatment. The relationship analysis revealed that controlling antibiotic discharge was crucial for managing AMR, as antibiotics were closely related to both ARGs and bacteria associated with their emergence. The results showed that the newly developed treatment process could reduce AMR caused by BAC treatment while ensuring effluent quality. Therefore, O3/PMS-BAC is a promising alternative to BAC treatment for future applications.

A pilot study on improvements in attention function in major depressive disorder after 12 weeks of escitalopram monotherapy or combined treatment with agomelatine.

Objective: This study aimed to explore both impairments in attention function in patients with major depressive disorder (MDD) and the efficacy of escitalopram monotherapy or combination therapy with agomelatine. Methods: A total of 54 patients with MDD and 46 healthy controls (HCs) were included. Patients were treated with escitalopram for 12 weeks; those who presented with severe sleep impairments were also given agomelatine. Participants were evaluated using the Attention Network Test (ANT), which included tests of alerting, orienting, and executive control networks. Concentration, instantaneous memory, and resistance to information interference were tested using the digit span test, and the logical memory test (LMT) was used to evaluate abstract logical thinking. The Hamilton Depression Rating Scale-17 items, Hamilton Anxiety Rating Scale, and Pittsburgh Sleep Quality Index were used to assess depression, anxiety, and sleep quality, respectively. Patients with MDD were assessed at the end of weeks 0, 4, 8, and 12. HCs were assessed once at baseline. Results: Compared with HCs, patients with MDD showed significantly different alerting, orienting, and executive control functions of attention networks. Treatment with escitalopram alone or combined with agomelatine significantly improved LMT scores at the end of weeks 4, 8, and 12 and restored scores to the level of HCs at the end of week 8. Total Toronto Hospital Test of Alertness scores in patients with MDD increased significantly after 4 weeks of treatment. The ANT executive control reaction time in patients with MDD decreased significantly after 4 weeks of treatment, with this decrease lasting until the end of week 12, but scores did not return to the levels of HCs. Combined treatment with escitalopram and agomelatine led to more improvement in ANT orienting reaction time and was accompanied by a greater reduction of total scores on the Hamilton Depression Rating Scale-17 items and Hamilton Anxiety Rating Scale compared with escitalopram monotherapy. Conclusions: Patients with MDD showed overall impairments in three domains of attention networks as well as the LMT and a test of subjective alertness. Escitalopram monotherapy significantly improved the LMT scores and the executive control function scores in the ANT at the end of the fourth week of treatment, and the improvement was more extensive with combined escitalopram and agomelatine treatment.

Characteristics of the formation and toxicity index of nine newly identified brominated disinfection byproducts during wastewater ozonation.

Ozonation plays an important role in wastewater treatment for reuse. However, the toxicity of wastewater treated with ozone considerably increases with bromide (Br-) concentration >100 µg/L. Nine newly identified brominated disinfection byproducts (Br-DBPs) that are highly toxic in ozonated Br--containing wastewater were found in our recent work, including 2-bromostyrene, 1-bromo-1-phenylethylene, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-bromophenylacetonitrile, 3-bromophenylacetonitrile, 4-bromophenylacetonitrile, and 2,4,6-tribromophenol. In the present study, the formation and calculated toxicity index of the nine newly identified Br-DBPs were evaluated. The correlations between the water quality index and the formation of nine Br-DBPs were also analyzed. With the increase of ozone dosage, the concentrations of bromostyrenes, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-bromophenylacetonitrile, and 2,4,6-tribromophenyl in the ozonated samples gradually increased. With the increase of Br- concentration, the concentrations of bromostyrene, 2-bromobenzaldehyde, and 2,4,6-tribromophenol gradually increased. With the increase of NH4+ concentration, the concentrations of bromophenylacetonitriles gradually increased. Among the nine Br-DBPs, the bromophenylacetonitriles and 2,4,6-tribromophenol contributed the most to the cytotoxicity index, 2,4,6-tribromophenol and bromostyrenes contributed the most to the genotoxicity index, and bromophenylacetonitriles and bromostyrenes contributed the most to the oxidative damage index. The dissolved organic carbon levels strongly correlated with the formation of 3-bromophenylacetonitrile and 4-bromophenylacetonitrile, and the fluorescence I-V region intensity integral was correlated with the formation of 4-bromobenzaldehyde and 2,4,6-tribromophenol. The results of the present study clarified the formation potential of the nine widely existing newly identified Br-DBPs, confirmed the high calculated toxicity indices, and are of great value for future research on Br-DBPs.

Metformin use is associated with a reduced risk of cognitive impairment in adults with diabetes mellitus: A systematic review and meta-analysis.

Objective: Controversy exists regarding the impact of metformin and whether it prevents or promotes the incidence of cognitive dysfunction. This systematic review and meta-analysis were conducted to identify the effect of metformin therapy on cognitive function in patients with diabetes. Methods: Electronic databases (PubMed, EMBASE, PsycINFO, the Cochrane Library, and Web of Science) were systematically searched by two investigators from the date of inception until March 1, 2022. The study followed PRISMA guidelines. Inclusion criteria were defined according to the PECOS model. Eligible studies investigated cognitive dysfunction in metformin users compared with non-users in adults with diabetes. Only observational study designs (such as cohort, cross-section, and case-control) were included. Results: A systematic search identified 1,839 articles, of which 28 (17 cohort, 8 case-control, and 3 cross-sectional studies) were included in the meta-analysis. Metformin reduced the occurrence of cognitive impairment in patients with diabetes [unadjusted hazard ratio (HR) = 0.67, 95% CI: 0.62-0.73; adjusted hazard ratio (aHR) = 0.92, 95% CI: 0.85-0.99]. In addition, the use of metformin was associated with a decreased risk of dementia (HR = 0.64, 95% CI: 0.59-0.69; aHR = 0.90, 95% CI: 0.84-0.96), while a random-effects meta-analysis indicated no significant effect of metformin on the risk of Alzheimer's disease (AD) (HR = 0.85, 95% CI: 0.60-1.22; aHR = 1.10, 95% CI: 0.95-1.28). Conclusion: Metformin therapy decreased the occurrence risk of cognitive decline in patients with diabetes mellitus. Moreover, the use of metformin by adults with diabetes for the prevention of dementia, but not AD, is supported by the available evidence.

Intestinal Gastrin/CCKBR (Cholecystokinin B Receptor) Ameliorates Salt-Sensitive Hypertension by Inhibiting Intestinal Na+/H+ Exchanger 3 Activity Through a PKC (Protein Kinase C)-Mediated NHERF1 and NHERF2 Pathway.

BACKGROUND: The present study directly tested the crucial role of intestinal gastrin/CCKBR (cholecystokinin B receptor) in the treatment of salt-sensitive hypertension. METHODS: Adult intestine-specific Cckbr-knockout mice (Cckbrfl/fl villin-Cre) and Dahl salt-sensitive rats were studied on the effect of high salt intake (8% NaCl, 6-7 weeks) on intestinal Na+/H+ exchanger 3 expression, urine sodium concentration, and blood pressure. High-salt diet increased urine sodium concentration and systolic blood pressure to a greater extent in Cckbrfl/fl villin-Cre mice and Dahl salt-sensitive rats than their respective controls, Cckbrfl/fl villin mice and SS13BN rats. We constructed gastrin-SiO2 microspheres to enable gastrin to stimulate specifically and selectively intestinal CCKBR without its absorption into the circulation. RESULTS: Gastrin-SiO2 microspheres treatment prevented the high salt-induced hypertension and increase in urine Na concentration by inhibiting intestinal Na+/H+ exchanger 3 trafficking and activity, increasing stool sodium without inducing diarrhea. Gastrin-mediated inhibition of intestinal Na+/H+ exchanger 3 activity, related to a PKC (protein kinase C)-mediated activation of NHERF1 and NHERF2. CONCLUSIONS: These results support a crucial role of intestinal gastrin/CCKBR in decreasing intestinal sodium absorption and keeping the blood pressure in the normal range. The gastrointestinal administration of gastrin-SiO2 microspheres is a promising and safe strategy to treat salt-sensitive hypertension without side effects.

Adjunctive accelerated repetitive transcranial magnetic stimulation for older patients with depression: A systematic review.

Objective: We performed this systemic review to investigate the therapeutic potential and safety of adjunctive accelerated repetitive transcranial magnetic stimulation (aTMS) for older patients with depression. Methods: We included published randomized clinical trials (RCTs) and observational studies targeting adjunctive aTMS for older patients with depression. Results: Two open-label self-controlled studies (n = 29) fulfilled the criteria for inclusion. The included studies reported significant improvements in depressive symptoms from baseline to post-aTMS (all Ps < 0.05). One study reported a dropout rate of 10.5% (2/19). Mild headache was the most common adverse reaction. Conclusion: The currently available evidence from two open-label self-controlled studies indicates that adjunctive aTMS is a safe and effective therapy for older patients with depression.

Mitochondrial Phylogenomics Suggests Complex Evolutionary Pattern of Pronotal Foliaceous Mimicry in Hierodulinae (Mantodea: Mantidae), with Description of a New Species of Rhombodera Burmeister, 1838 from China.

Hierodulinae is a species-rich mantid subfamily, with some species bearing a notable leaf-like pronotum. However, the evolutionary pattern and taxonomic significance of the leaf-like pronotum are largely unknown. Here, we present a phylogenomic analysis of the Hierodulinae genera Rhombodera Burmeister, 1838, and Hierodula Burmeister, 1838 based on mitochondrial genomes. We also describe a new species, namely Rhombodera hyalina sp. nov. from Guangxi, China. Our phylogenetic result, together with the evidence from male genitalia, suggests the division of the Oriental Hierodula and Rhombodera complex into three clades. We find a complex pattern on the evolution of the leaf-like pronotum, which is present in at least five lineages, respectively, of the above three clades.

Comprehensive GC×GC-qMS with a mass-to-charge ratio difference extraction method to identify new brominated byproducts during ozonation and their toxicity assessment.

Ozonation might increase the risk of wastewater due to byproduct formation, especially in the presence of bromide. In this study, a new analytical method was developed to identify new brominated disinfection byproducts (Br-DBPs) during ozonation, using comprehensive two-dimensional gas chromatography-single quadrupole mass spectrometry (GC×GC-qMS) connected with an electron capture detector in parallel. The obtained data were analyzed using a mass-to-charge ratio (m/z) difference extraction method. Over 1304 DBPs were detected in an ozonated phenylalanine solution. Further screening of 635 DBPs was conducted using the m/z difference extraction method. Finally, the structures for 12 Br-DBPs were confirmed and for 4 Br-DBPs were tentatively proposed by comparison with the NIST library and standard compounds. Eight of the confirmed Br-DBPs are first reported and identified: 2-bromostyrene, 1-bromo-1-phenylethylene, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-bromophenylacetonitrile, 3-bromophenylacetonitrile and 4-bromophenylacetonitrile. These DBPs and 2,4,6-tribromophenol were detected at nanogram- to microgram-per-liter concentrations during ozonation of authentic water samples like algal bloom waters, wastewater treatment plant effluents, and surface water. The toxicities of these compounds were generally higher than that of bromate. The developed analytical method is a powerful technique for analyzing complex compounds and provides a novel way of identifying byproducts in future studies.

Effect of Swelling by Organic Solvent on Structure, Pyrolysis, and Methanol Extraction Performance of Hefeng Bituminous Coal.

N-methyl-2-pyrrolidone (NMP), pyridine (Py), tetrahydrofuran (THF), and tetralin (THN) were used to swell Hefeng acid-washed bituminous coal (HBCAC). The swelling effect on HBCAC by each solvent is different, among which NMP presented well swelling performance, with a swelling degree of 2.11. FTIR results showed that acid washing and swelling processes presented a marginal effect on HBC, and there was no damage to the macromolecule structure of the coal. TG-DTG profiles of the swollen coals illustrated that the total weight loss of each sample was lower than that of the acid-washing one, while the temperature of the maximum weight loss rate peak was almost unchanged, around 445 °C. Extract yield by methanol followed the order of HBCAC > HBC > HBCAC-NMP (swelled by NMP), showing that acid washing promoted the methanol extraction process, with a higher extract yield of 3.21%, which is twice that of HBC (1.66%).

Surrogates for on-line monitoring of the attenuation of trace organic contaminants during advanced oxidation processes for water reuse.

The large number of trace organic contaminants (TrOCs) in wastewater has resulted in severe concerns to human health. Ozonation and UV/H2O2 are widely used to remove TrOCs in wastewater treatment process. Owing to the trace concentrations of TrOCs in wastewater, real-time monitoring of the abatement efficiency of TrOCs through ozonation and UV/H2O2 is quite challenging. Instead of a direct measurement of all the TrOCs, the research community has begun to use different surrogates to monitor the attenuation of TrOCs during AOPs. Various surrogates have been developed over the past few decades. In this review, the different types of surrogates are summarized, including ultraviolet spectroscopy and fluorescence spectroscopy. Strong linear correlations have been found for the removal of TrOCs using AOPs, and the abatement of UV absorption spectroscopy at 254 nm or total fluorescence (TF). Moreover, a two-phase linear correlation can better describe the ozone-resistant TrOCs compared with a single linear correlation. Two different kinds of predictive models exist that use surrogates as the input for ozonation: the regression model and kinetic model. The development of the models requires a further understanding of the impacts of water quality, seasonal variations, and storm events on the kinetic parameters. For the in situ monitoring system, the light-emitting diode (LED) is one of the most promising light sources, although the sensitivity and accuracy still need to be improved.