Impact of genomic and epigenomic alterations of multigene on a multicancer pedigree.

BACKGROUND: Germline mutations have been identified in a small number of hereditary cancers, but the genetic predisposition for many familial cancers remains to be elucidated. METHODS: This study identified a Chinese pedigree that presented different cancers (breast cancer, BRCA; adenocarcinoma of the esophagogastric junction, AEG; and B-cell acute lymphoblastic leukemia, B-ALL) in each of the three generations. Whole-genome sequencing and whole-exome sequencing were performed on peripheral blood or bone marrow and cancer biopsy samples. Whole-genome bisulfite sequencing was conducted on the monozygotic twin brothers, one of whom developed B-ALL. RESULTS: According to the ACMG guidelines, bioinformatic analysis of the genome sequencing revealed 20 germline mutations, particularly mutations in the DNAH11 (c.9463G > A) and CFH (c.2314G > A) genes that were documented in the COSMIC database and validated by Sanger sequencing. Forty-one common somatic mutated genes were identified in the cancer samples, displaying the same type of single nucleotide substitution Signature 5. Meanwhile, hypomethylation of PLEK2, MRAS, and RXRA as well as hypermethylation of CpG island associated with WT1 was shown in the twin with B-ALL. CONCLUSIONS: These findings reveal genomic alterations in a pedigree with multiple cancers. Mutations found in the DNAH11, CFH genes, and other genes predispose to malignancies in this family. Dysregulated methylation of WT1, PLEK2, MRAS, and RXRA in the twin with B-ALL increases cancer susceptibility. The similarity of the somatic genetic changes among the three cancers indicates a hereditary impact on the pedigree. These familial cancers with germline and somatic mutations, as well as epigenomic alterations, represent a common molecular basis for many multiple cancer pedigrees.

YKL-40 Knockdown Decreases Oxidative Stress Damage in Ovarian Granulosa Cells.

Background: Oxidative stress has been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). To develop novel antioxidant drugs, it is necessary to explore the key regulatory molecules involved in oxidative stress in PCOS. Plasma YKL-40 levels are elevated in patients with PCOS; however, its role remains unclear. Methods: The follicular fluids of 20 women with PCOS and 12 control subjects with normal ovarian function were collected, and YKL-40 in follicular fluids was measured by enzyme-linked immunosorbent assay. A letrozole-induced PCOS rat model was established and the expression level of YKL-40 in the ovaries was detected by immunohistochemistry. KGN cells were treated with H2O2 to generate an ovarian granulosa cell (OGC) model of oxidative stress. The siRNA was transfected into the cells for knockdown. The effect of YKL-40 knockdown on H2O2-treated KGN cells was evaluated by measuring proliferation, apoptosis, activities of T-SOD, GSH-Px, and CAT, levels of MDA, IL-1ß, IL-6, IL-8, and TNF-α, and the PI3K/AKT/NF-κB signaling pathway. Results: YKL-40 levels were elevated in the follicular fluids of women with PCOS compared with control subjects with normal ovarian function. The expression level of YKL-40 in the ovaries of rats with PCOS is obviously higher than that in the ovaries of the control group rats. H2O2 treatment enhanced YKL-40 mRNA expression and protein secretion. YKL-40 knockdown enhanced cell proliferation and antioxidant capacity while decreasing apoptosis and inflammatory factor levels in KGN cells following H2O2 treatment. The knockdown activated the PI3K/AKT signaling pathway and suppressed NF-κB nuclear translocation from the cytoplasm. Conclusion: YKL-40 levels were elevated in the follicular fluids of women with PCOS and the ovaries of rats with PCOS. YKL-40 expression can be induced by oxidative stress, and YKL-40 knockdown can decrease oxidative stress damage in OGCs.

Oxidative Transformation of Nafion-Related Fluorinated Ether Sulfonates: Comparison with Legacy PFAS Structures and Opportunities of Acidic Persulfate Digestion for PFAS Precursor Analysis.

The total oxidizable precursor (TOP) assay has been extensively used for detecting PFAS pollutants that do not have analytical standards. It uses hydroxyl radicals (HO•) from the heat activation of persulfate under alkaline pH to convert H-containing precursors to perfluoroalkyl carboxylates (PFCAs) for target analysis. However, the current TOP assay oxidation method does not apply to emerging PFAS because (i) many structures do not contain C-H bonds for HO• attack and (ii) the transformation products are not necessarily PFCAs. In this study, we explored the use of classic acidic persulfate digestion, which generates sulfate radicals (SO4-•), to extend the capability of the TOP assay. We examined the oxidation of Nafion-related ether sulfonates that contain C-H or -COO-, characterized the oxidation products, and quantified the F atom balance. The SO4-• oxidation greatly expanded the scope of oxidizable precursors. The transformation was initiated by decarboxylation, followed by various spontaneous steps, such as HF elimination and ester hydrolysis. We further compared the oxidation of legacy fluorotelomers using SO4-• versus HO•. The results suggest novel product distribution patterns, depending on the functional group and oxidant dose. The general trends and strategies were also validated by analyzing a mixture of 100000- or 10000-fold diluted aqueous film-forming foam (containing various fluorotelomer surfactants and organics) and a spiked Nafion precursor. Therefore, (1) the combined use of SO4-• and HO• oxidation, (2) the expanded list of standard chemicals, and (3) further elucidation of SO4-• oxidation mechanisms will provide more critical information to probe emerging PFAS pollutants.

Enhancing Aqueous Chlorate Reduction Using Vanadium Redox Cycles and pH Control.

Chlorate (ClO3-) is a toxic oxyanion pollutant from industrial wastes, agricultural applications, drinking water disinfection, and wastewater treatment. Catalytic reduction of ClO3- using palladium (Pd) nanoparticle catalysts exhibited sluggish kinetics. This work demonstrates an 18-fold activity enhancement by integrating earth-abundant vanadium (V) into the common Pd/C catalyst. X-ray photoelectron spectroscopy and electrochemical studies indicated that VV and VIV precursors are reduced to VIII in the aqueous phase (rather than immobilized on the carbon support) by Pd-activated H2. The VIII/IV redox cycle is the predominant mechanism for the ClO3- reduction. Further reduction of chlorine intermediates to Cl- could proceed via VIII/IV and VIV/V redox cycles or direct reduction by Pd/C. To capture the potentially toxic V metal from the treated solution, we adjusted the pH from 3 to 8 after the reaction, which completely immobilized VIII onto Pd/C for catalyst recycling. The enhanced performance of reductive catalysis using a Group 5 metal adds to the diversity of transition metals (e.g., Cr, Mo, Re, Fe, and Ru in Groups 6-8) for water pollutant treatment via various unique mechanisms.

Preparation and Synergy of Supported Ru0 and Pd0 for Rapid Chlorate Reduction at pH 7.

Chlorate (ClO3-) is a common water pollutant due to its gigantic scale of production, wide applications in agriculture and industry, and formation as a toxic byproduct in various water treatment processes. This work reports on the facile preparation, mechanistic elucidation, and kinetic evaluation of a bimetallic catalyst for highly active ClO3- reduction into Cl-. Under 1 atm H2 and 20 °C, PdII and RuIII were sequentially adsorbed and reduced on a powdered activated carbon support, affording Ru0-Pd0/C from scratch within only 20 min. The Pd0 particles significantly accelerated the reductive immobilization of RuIII as >55% dispersed Ru0 outside Pd0. At pH 7, Ru-Pd/C shows a substantially higher activity of ClO3- reduction (initial turnover frequency >13.9 min-1 on Ru0; rate constant at 4050 L h-1 gmetal-1) than reported catalysts (e.g., Rh/C, Ir/C, Mo-Pd/C) and the monometallic Ru/C. In particular, Ru-Pd/C accomplished the reduction of concentrated 100 mM ClO3- (turnover number > 11,970), whereas Ru/C was quickly deactivated. In the bimetallic synergy, Ru0 rapidly reduces ClO3- while Pd0 scavenges the Ru-passivating ClO2- and restores Ru0. This work demonstrates a simple and effective design for heterogeneous catalysts tailored for emerging water treatment needs.

Accelerating Catalytic Oxyanion Reduction with Inert Metal Hydroxides.

Adding CrIII or AlIII salts into the water suspension of platinum group metal (PGM) catalysts accelerated oxyanion pollutant reduction by up to 600%. Our initial attempts of adding K2CrVIO4, K2CrVI2O7, or KCrIII(SO4)2 into Pd/C enhanced BrO3- reduction with 1 atm H2 by 6-fold. Instrument characterizations and kinetic explorations collectively confirmed the immobilization of reduced CrVI as CrIII(OH)3 on the catalyst surface. This process altered the ζ-potentials from negative to positive, thus substantially enhancing the Langmuir-Hinshelwood adsorption equilibrium constant for BrO3- onto Pd/C by 37-fold. Adding AlIII(OH)3 from alum at pH 7 achieved similar enhancements. The Cr-Pd/C and Al-Pd/C showed top-tier efficiency of catalytic performance (normalized with Pd dosage) among all the reported Pd catalysts on conventional and nanostructured support materials. The strategy of adding inert metal hydroxides works for diverse PGMs (palladium and rhodium), substrates (BrO3- and ClO3-), and support materials (carbon, alumina, and silica). This work shows a simple, inexpensive, and effective example of enhancing catalyst activity and saving PGMs for environmental applications.

Self-assembly of alkyl-perylenebisdiimide-DNA amphiphiles and control of their morphology through cyclodextrin-based host-guest interaction.

Amphiphilic alkyl-perylenebisdiimide-DNA hybrids self-assemble into spherical micelles and transform into nanofibers upon the addition of ß-cyclodextrins due to host-guest interaction. A competitive guest can induce the nanofibers to reversibly change back to spherical micelles. Both spherical micelles and nanofibers can anchor functional molecules at the corona through DNA hybridization.

Factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection in older women.

Objective: To analyse the factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in older women, and to establish a risk prediction model. Methods: A total of 425 patients receiving IVF/ICSI from March 2018 to March 2020 were divided into pregnancy group (n=194) and non-pregnancy group (n=231). The factors affecting the outcomes of IVF/ICSI were explored by univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed. Results: The two groups had significantly different age, body mass index, dysmenorrhea, parity, times of full-term births, history of cesarean section, basal follicle stimulating hormone, basal antral follicle count (AFC), number of high-quality embryos, and basal estradiol, luteinizing hormone and endometrial thickness on the day of human chorionic gonadotropin (HCG) administration (P<0.05). Age ≥40 years old, dysmenorrhea, history of cesarean section, basal AFC<9, number of high-quality embryos <4, and endometrial thickness on the day of HCG administration <11 mm led to IVF/ICSI failure. The established model exhibited high calibration and discrimination degrees in predicting the outcome of IVF/ICSI. Conclusion: The risk prediction model for the pregnancy outcome of IVF/ICSI in older women helps evaluate the fertility probability and risk, providing references for formulating reasonable assisted reproduction plans.

Substantial defluorination of polychlorofluorocarboxylic acids triggered by anaerobic microbial hydrolytic dechlorination.

Chlorinated polyfluorocarboxylic acids (Cl-PFCAs) derived from the widely used chlorotrifluoroethylene (CTFE) polymers and oligomers may enter and influence the aquatic environment. Here, we report significant defluorination of Cl-PFCAs by an anaerobic microbial community via novel pathways triggered by anaerobic microbial dechlorination. Cl-PFCAs first underwent microbial reductive, hydrolytic, and eliminative dechlorination, and it was the hydrolytic dechlorination that led to significant spontaneous defluorination. Hydrolytic dechlorination was favored with increased Cl-substitutions. An isolated, highly enriched anaerobic defluorinating culture was dominated by two genomes closest to Desulfovibrio aminophilus and Sporomusa sphaeroides, both of which exhibited active defluorination of CTFE tetramer acid. It implies the critical role played by anaerobic non-respiratory hydrolytic dechlorination in the fate of chlorinated polyfluoro-chemicals in natural and engineered water environments. The greatly enhanced biodegradability by Cl-substitutions also sheds light on the design of cost-effective treatment biotechnologies, as well as alternative PFAS that are readily biodegradable and less toxic.

Sample-multiplexing approaches for single-cell sequencing.

Single-cell sequencing is widely used in biological and medical studies. However, its application with multiple samples is hindered by inefficient sample processing, high experimental costs, ambiguous identification of true single cells, and technical batch effects. Here, we introduce sample-multiplexing approaches for single-cell sequencing in transcriptomics, epigenomics, genomics, and multiomics. In single-cell transcriptomics, sample multiplexing uses variants of native or artificial features as sample markers, enabling sample pooling and decoding. Such features include: (1) natural genetic variation, (2) nucleotide-barcode anchoring on cellular or nuclear membranes, (3) nucleotide-barcode internalization to the cytoplasm or nucleus, (4) vector-based barcode expression in cells, and (5) nucleotide-barcode incorporation during library construction. Other single-cell omics methods are based on similar concepts, particularly single-cell combinatorial indexing. These methods overcome current challenges, while enabling super-loading of single cells. Finally, selection guidelines are presented that can accelerate technological application.

Accelerated Degradation of Perfluorosulfonates and Perfluorocarboxylates by UV/Sulfite + Iodide: Reaction Mechanisms and System Efficiencies.

The addition of iodide (I-) in the UV/sulfite system (UV/S) significantly accelerated the reductive degradation of perfluorosulfonates (PFSAs, CnF2n+1SO3-) and perfluorocarboxylates (PFCAs, CnF2n+1COO-). Using the highly recalcitrant perfluorobutane sulfonate (C4F9SO3-) as a probe, we optimized the UV/sulfite + iodide system (UV/S + I) to degrade n = 1-7 PFCAs and n = 4, 6, 8 PFSAs. In general, the kinetics of per- and polyfluoroalkyl substance (PFAS) decay, defluorination, and transformation product formations in UV/S + I were up to three times faster than those in UV/S. Both systems achieve a similar maximum defluorination. The enhanced reaction rates and optimized photoreactor settings lowered the EE/O for PFCA degradation below 1.5 kW h m-3. The relatively high quantum yield of eaq- from I- made the availability of hydrated electrons (eaq-) in UV/S + I and UV/I two times greater than that in UV/S. Meanwhile, the rapid scavenging of reactive iodine species by SO32- made the lifetime of eaq- in UV/S + I eight times longer than that in UV/I. The addition of I- also substantially enhanced SO32- utilization in treating concentrated PFAS. The optimized UV/S + I system achieved >99.7% removal of most PFSAs and PFCAs and >90% overall defluorination in a synthetic solution of concentrated PFAS mixtures and NaCl. We extended the discussion over molecular transformation mechanisms, development of PFAS degradation technologies, and the fate of iodine species.

Defluorination of Omega-Hydroperfluorocarboxylates (ω-HPFCAs): Distinct Reactivities from Perfluoro and Fluorotelomeric Carboxylates.

Omega-hydroperfluorocarboxylates (ω-HPFCAs, HCF2-(CF2)n-1-COO-) are commercially available in bulk quantities and have been applied in agrochemicals, fluoropolymer production, and semiconductor coating. In this study, we used kinetic measurements, theoretical calculations, model compound experiments, and transformation product analyses to reveal novel mechanistic insights into the reductive and oxidative transformation of ω-HPFCAs. Like perfluorocarboxylates (PFCAs, CF3-(CF2)n-1-COO-), the direct linkage between HCnF2n- and -COO- enables facile degradation under UV/sulfite treatment. To our surprise, the presence of the H atom on the remote carbon makes ω-HPFCAs more susceptible than PFCAs to decarboxylation (i.e., yielding shorter-chain ω-HPFCAs) and less susceptible to hydrodefluorination (i.e., H/F exchange). Like fluorotelomer carboxylates (FTCAs, CnF2n+1-CH2CH2-COO-), the C-H bond in HCF2-(CF2)n-1-COO- allows hydroxyl radical oxidation and limited defluorination. While FTCAs yielded PFCAs in all chain lengths, ω-HPFCAs only yielded -OOC-(CF2)n-1-COO- (major) and -OOC-(CF2)n-2-COO- (minor) due to the unfavorable ß-fragmentation pathway that shortens the fluoroalkyl chain. We also compared two treatment sequences-UV/sulfite followed by heat/persulfate and the reverse-toward complete defluorination of ω-HPFCAs. The findings will benefit the treatment and monitoring of H-containing per- and polyfluoroalkyl substance (PFAS) pollutants as well as the design of future fluorochemicals.

Near-Quantitative Defluorination of Perfluorinated and Fluorotelomer Carboxylates and Sulfonates with Integrated Oxidation and Reduction.

The UV-sulfite reductive treatment using hydrated electrons (eaq-) is a promising technology for destroying perfluorocarboxylates (PFCAs, CnF2n+1COO-) in any chain length. However, the C-H bonds formed in the transformation products strengthen the residual C-F bonds and thus prevent complete defluorination. Reductive treatments of fluorotelomer carboxylates (FTCAs, CnF2n+1-CH2CH2-COO-) and sulfonates (FTSAs, CnF2n+1-CH2CH2-SO3-) are also sluggish because the ethylene linker separates the fluoroalkyl chain from the end functional group. In this work, we used oxidation (Ox) with hydroxyl radicals (HO•) to convert FTCAs and FTSAs to a mixture of PFCAs. This process also cleaved 35-95% of C-F bonds depending on the fluoroalkyl chain length. We probed the stoichiometry and mechanism for the oxidative defluorination of fluorotelomers. The subsequent reduction (Red) with UV-sulfite achieved deep defluorination of the PFCA mixture for up to 90%. The following use of HO• to oxidize the H-rich residues led to the cleavage of the remaining C-F bonds. We examined the efficacy of integrated oxidative and reductive treatment of n = 1-8 PFCAs, n = 4,6,8 perfluorosulfonates (PFSAs, CnF2n+1-SO3-), n = 1-8 FTCAs, and n = 4,6,8 FTSAs. A majority of structures yielded near-quantitative overall defluorination (97-103%), except for n = 7,8 fluorotelomers (85-89%), n = 4 PFSA (94%), and n = 4 FTSA (93%). The results show the feasibility of complete defluorination of legacy PFAS pollutants and will advance both remediation technology design and water sample analysis.

A Bioinspired Molybdenum Catalyst for Aqueous Perchlorate Reduction.

Perchlorate (ClO4-) is a pervasive, harmful, and inert anion on both Earth and Mars. Current technologies for ClO4- reduction entail either harsh conditions or multicomponent enzymatic processes. Herein, we report a heterogeneous (L)Mo-Pd/C catalyst directly prepared from Na2MoO4, a bidentate nitrogen ligand (L), and Pd/C to reduce aqueous ClO4- into Cl- with 1 atm of H2 at room temperature. A suite of instrument characterizations and probing reactions suggest that the MoVI precursor and L at the optimal 1:1 ratio are transformed in situ into oligomeric MoIV active sites at the carbon-water interface. For each Mo site, the initial turnover frequency (TOF0) for oxygen atom transfer from ClOx- substrates reached 165 h-1. The turnover number (TON) reached 3840 after a single batch reduction of 100 mM ClO4-. This study provides a water-compatible, efficient, and robust catalyst to degrade and utilize ClO4- for water purification and space exploration.

LncRNA LINC01503 aggravates the progression of cervical cancer through sponging miR-342-3p to mediate FXYD3 expression.

Cervical cancer (CC), an aggressive malignancy, has a high risk of relapse and death, mainly occurring in females. Accumulating investigations have confirmed the critical role of long noncoding RNAs (lncRNAs) in diverse cancers. LncRNA LINC01503 has been reported as an oncogene in several cancers. Nonetheless, its role and molecular mechanism in CC have not been explored. In the present study, we found that FXYD3 expression was considerably up-regulated in CC tissues and cells. Moreover, FXYD3 deficiency conspicuously hampered cell proliferation and migration while facilitated cell apoptosis in CC cells. Subsequently, molecular mechanism experiments implied that FXYD3 was a downstream target gene of miR-342-3p, and FXYD3 expression was reversely mediated by miR-342-3p. Moreover, we discovered that LINC01503 acted as the endogenous sponge for miR-342-3p. Besides, LINC01503 negatively regulated miR-342-3p expression and positively regulated FXYD3 expression in CC. Rescue assays revealed that LINC01503 depletion-induced repression on CC progression could be partly recovered by miR-342-3p inhibition, and then the co-transfection of sh-FXYD3#1 rescued this effect. Conclusively, LINC01503 aggravated CC progression through sponging miR-342-3p to mediate FXYD3 expression, providing promising therapeutic targets for CC patients.

Chemical characteristics and source apportionment of PM2.5 using PMF modelling coupled with 1-hr resolution online air pollutant dataset for Linfen, China.

The chemical species in PM2.5 and air pollutant concentration data with 1-hr resolution were monitored synchronously between 15 November 2018 and 20 January 2019 in Linfen, China, which were analysed for multiple temporal patterns, and PM2.5 source apportionment using positive matrix factorisation (PMF) modelling coupled with online chemical species data was conducted to obtain the apportionment results of distinct temporal patterns. The mean concentration of PM2.5 was 124 µg/m3 during the heating period, and NO3- and organic carbon (OC) were the dominant species. The concentrations and percentages of NO3-, SO42-, and OC increased notably during the growth periods of haze events, thereby indicating secondary particle formation. Six factors were identified by the PMF model during the heating period, including vehicular emissions (VE: 26.5%), secondary nitrate (SN: 16.5%), coal combustion and industrial emissions (CC&IE: 25.7%), secondary sulfate and secondary organic carbon (SS&SOC: 24.4%), biomass burning (BB: 1.0%), and crustal dust (CD: 5.9%). The primary sources of PM2.5 on clean days were CD (33.3%), VE (23.1%), and SS&SOC (20.6%), while they were CC&IE (32.9%) and SS&SOC (28.3%) during the haze events. The contributions of secondary sources and CC&IE increased rapidly during the growth periods of haze events, while that of CD increased during the dissipation period. Diurnal variations in the contribution of secondary sources were mainly related to the accumulation and transformation of corresponding gaseous precursors. In comparison, contributions of CC&IE and VE varied as a function of the domestic heating load and peak levels occurred during the morning and evening rush hours. High contributions of major sources (CC&IE and SS&SOC) during haze events originated mainly from the north and south, while high contribution of a major source (CD) on clean days was from the northwest.

MiR-1258 promotes the apoptosis of cervical cancer cells by regulating the E2F1/P53 signaling pathway.

OBJECTIVE: Cervical cancer is the most common malignant tumor in gynaecology with high mortality. MiRNA has been reported to regulate cell biological processes in cervical cancer. This study aimed to explore the expression of miR-1258 and role of miR-1258 by targeting E2F1 in cervical cancer cells. METHODS: The expression of miR-1258 and E2F1 in cervical cancer cells and transfection effects was determined by RT-qPCR analysis. The expression of E2F1, MMP2, MMP7, MMP9, Bcl2, Bax, cleaved caspase3, caspase3, KI67, p-AKT, cyclinD1, CDK2, P53 and AKT in cervical cancer cells was detected by western blot analysis. The proliferation, invasion, migration and apoptosis were respectively analyzed by CCK-8 assay, transwell assay, wound healing assay and flow cytometry analysis. E2F1 was a potential target of miR-1258, which demonstrated by a dual-luciferase reporter assay. RESULTS: miR-1258 expression was decreased while E2F1 expression was increased in cervical cancer cells. MiR-1258 overexpression could down-regulate the E2F1 expression. Overexpression of miR-1258 inhibited the proliferation, invasion and migration and promoted the apoptosis of cervical cancer cells by AKT and P53 signal pathway. And, Overexpression of miR-1258 also suppressed the tumor growth by AKT and P53 signal pathway. Overexpression of E2F1 reduced the inhibition effects of miR-1258 in cervical cancer. CONCLUSION: Taken together, miR-1258 overexpression exerts its inhibition effects on the proliferation, invasion and migration and promotion effects on the apoptosis of cervical cancer cells by targeting the E2F1, which might provide new ideas for clinical treatment of cervical cancer.

Efficacy of orthodontic and orthognathic treatment for oral and maxillofacial deformities.

BACKGROUND: This study aims to assess the efficacy and safety of orthodontic and orthognathic treatment (OOT) for patients with oral and maxillofacial deformities (OMDF) systematically. METHODS: This study will comprehensively search Cochrane Library, PubMed, EMBASE, Scopus, Web of Science, PsycINFO, Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their inceptions to the July 1, 2019. Grey literature will be explored via searching dissertations, Google scholar and conference abstracts. Two team members will independently perform all citations, data extraction, and methodological quality. We will also utilize RevMan 5.3 Software for statistical analysis. RESULTS: This study will provide high quality evidence of OOT for OMDF. The primary outcomes consist of number of patients cured; proportion of patients healed; and time to complete healing within trial period. Secondary outcomes include quality of life (often assessed as any relevant scales, such as 36-Item Short Form Survey), costs, and complications. CONCLUSION: This study will provide evidence for judging whether OOT is effective treatment for OMDF. SYSTEMATIC REVIEW REGISTRATION: CRD42019144610.

Chinese herbal medicine Qinggongshoutao for the treatment of amnestic mild cognitive impairment: A 52-week randomized controlled trial.

INTRODUCTION: This randomized, double-blind trial aimed to test effect of a Chinese herbal medicine, Qinggongshoutao (QGST) pill, on the cognition and progression of amnestic mild cognitive impairment (aMCI). METHODS: Patients with aMCI were randomly assigned to receive QGST, Ginkgo biloba extract, or placebo for 52 weeks. The primary outcome measures were progression to possible or probable Alzheimer's disease (AD) and change in Alzheimer's Disease Assessment Scale-cognitive subscale scores; secondary outcome measures included assessments for cognition and function. RESULTS: Total 350 patients were enrolled, possible or probable AD developed in 10. There were significant differences in the probability of progression to AD in the QGST group (1.15%) compared with placebo group (10%). There was significant difference in Alzheimer's Disease Assessment Scale-cognitive subscale scores in favor of QGST over the placebo group. Secondary outcome measure (Mini-Mental State Examination) also showed benefit in QGST at end point. DISCUSSION: In patients with aMCI, QGST showed lower AD progression rate than placebo at 8.85%, and may have benefit on global cognition.

Astragaloside IV attenuates inflammatory injury and promotes odontoblastic differentiation in lipopolysaccharide-stimulated MDPC-23 cells and rat pulpitis.

BACKGROUND: Astragaloside IV (AS-IV), a natural herbal compound from Astragalus membranaceus, has inhibitory effects on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, and RANKL signal helps to regulate odontoblast differentiation. However, whether and how AS-IV affects odontoblastic differentiation remains unclear. METHODS: Lipopolysaccharide (LPS)-stimulated MDPC-23 cells and rat pulpitis were treated with AS-IV, cell viability, and LDH leakage was analyzed by CCK-8 assay and LDH Leakage assay. The production of TNF-α and IL-6 was determined by ELISA and qRT-PCR assay. The expression of alkaline phosphatase (ALP) was detected using an ALP assay kit, and the expression of dentin sialophos-phoprotein (DSPP), dentin matrix protein-1 (DMP1), basic fibroblast growth factor (FGF2), and phosphorylated extracellular signal-regulated kinase (p-ERK) was determined by western blot. RESULTS: AS-IV dose dependently increased in cell viability and decreased the overproduction of TNF-α and IL-6 in LPS-stimulated MDPC-23 cells. AS-IV also counteracted LPS-induced downregulation of ALP, DSPP, and DMP1 in MDPC-23 cells. Furthermore, AS-IV significantly decreased the expression of FGF2 and p-ERK in LPS-stimulated MDPC-23 cells. More important, the addition of FGF2 partly neutralized AS-IV-mediated inhibition of FGF2/ERK signaling, abolished AS-IV-induced reduction of TNF-α and IL-6, and counteracted AS-IV-induced upregulation of DSPP and DMP-1 in these cells. Meanwhile, AS-IV inhibited the excessive production of TNF-α and IL-6, suppressed the downregulation of DSPP and DMP1, and disturbed the up-regulation of FGF2 and p-ERK in the pulp tissues of rat pulpitis model. CONCLUSIONS: AS-IV exerted anti-inflammatory and pro-differentiation effects in LPS-stimulated MDPC-23 cells and rat pulpitis via inhibiting the FGF2/ERK signaling pathway.