Rapid Information Retrieval from DNA Storage with Microfluidic Very Large-Scale Integration Platform.

Due to its high information density, DNA is very attractive as a data storage system. However, a major obstacle is the high cost and long turnaround time for retrieving DNA data with next-generation sequencing. Herein, the use of a microfluidic very large-scale integration (mVLSI) platform is described to perform highly parallel and rapid readout of data stored in DNA. Additionally, it is demonstrated that multi-state data encoded in DNA can be deciphered with on-chip melt-curve analysis, thereby further increasing the data content that can be analyzed. The pairing of mVLSI network architecture with exquisitely specific DNA recognition gives rise to a scalable platform for rapid DNA data reading.

Spatiotemporal variation and driving factor of vegetation coverage from 2000 to 2020 in southern Jiangxi Province, China.

Vegetation plays a critical role in the water and carbon cycling and energy flow, serving as an indicator for regulating land carbon balance and reflecting climate change and human activities. We analyzed the spatiotemporal variations of normalized difference vegetation index (NDVI) during the growing season in southern Jiangxi from 2000 to 2020, using statistical methods, including the Mann-Kendall test, Theil-Sen Median analysis, Hurst index, and coefficient of variation. We employed the geodetector model to comprehensively assess the impacts of climate, topography, soil and human factors on spatial differentiation of vegetation NDVI. The results showed NDVI exhibited an upward fluctuating trend with a rate of 0.003 per year from 2000 to 2020. The proportion of high-grade and medium-high-grade NDVI areas were 55.8% and 41.9%, respectively, while the areas with low and relatively low fluctuations accounted for 92.3%. The proportions of areas showing extremely significant improvement and significant improvement were 40.4% and 19.4%, respectively. In contrast, the combined proportion of areas displaying extremely significant degradation and significant degradation was only 2.2%. The proportions of areas demonstrating continuous improvement and future improvement were 28.0% and 60.2%, respectively. Elevation, precipitation, relative humidity, temperature, landform type, land use type, population density, and nighttime light were identified as the major factors for the vairations of NDVI in the study area, followed by slope, soil type, and GDP, while slope aspect and vegetation type had indirect influence. Throughout the study period, NDVI in southern Jiangxi was overall stable, with future changes primarily indicating improvement. Notably, human factors such as land use type, population density, and nighttime light index exhibited an upward trend in their impacts on NDVI.

Melt-Encoded-Tags for Expanded Optical Readout in Digital PCR (METEOR-dPCR) Enables Highly Multiplexed Quantitative Gene Panel Profiling.

Digital PCR (dPCR) is an important tool for precise nucleic acid quantification in clinical setting, but the limited multiplexing capability restricts its applications for quantitative gene panel profiling. Here, this work describes melt-encoded-tags for expanded optical readout in digital PCR (METEOR-dPCR), a simple two-step assay that enables simultaneous quantification of a large panel of arbitrary genes in a dPCR platform. Target genes are quantitatively converted into DNA tags with unique melting temperatures through a ligation approach. These tags are then counted and distinguished by their melt-curve profiles on a dPCR platform. A multiplexing capacity of M^N, where M is the number of resolvable melting temperature and N is the number of fluorescence channel, can be achieved. This work validates METEOR-dPCR with simultaneous DNA copy number profiling of 60 targets using dPCR in cancer cells, and demonstrates its sensitivity for estimating tumor fraction in mixed tumor and normal DNA samples. The rapid, quantitative, and highly multiplexed METEOR-dPCR assay will have wide appeal for many clinical applications.

Rapid Single-Round Pool Testing of Infectious Disease Enabled by Multicolor Digital Melting PCR.

Pooled nucleic acid amplification test is a promising strategy to reduce cost and resources for screening large populations for infectious disease. However, the benefit of pooled testing is reversed when disease prevalence is high, because of the need to retest each sample to identify infected individual when a pool is positive. Split, Amplify, and Melt analysis of Pooled Assay (SAMPA) is presented, a multicolor digital melting PCR assay in nanoliter chambers that simultaneously identify infected individuals and quantify their viral loads in a single round of pooled testing. This is achieved by early sample tagging with unique barcodes and pooling, followed by single molecule barcode identification in a digital PCR platform using a highly multiplexed melt curve analysis strategy. The feasibility is demonstrated of SAMPA for quantitative unmixing and variant identification from pools of eight synthetic DNA and RNA samples corresponding to the N1 gene, as well as from heat-inactivated SARS-CoV-2 virus. Single round pooled testing of barcoded samples with SAMPA can be a valuable tool for rapid and scalable population testing of infectious disease.

Mechanical stretch aggravates vascular smooth muscle cell apoptosis and vascular remodeling by downregulating EZH2.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2) was recently found to play an important role in cardiovascular disease. However, the role of EZH2 in vascular remodeling induced by mechanical stretch is poorly understood. The aim of the present work was to investigate the role of EZH2 in regulating smooth muscle cell function through mechanical stretch assays and to explore the underlying mechanisms. METHODS: WT C57BL/6 J mice underwent sham surgery or abdominal aortic constriction. The level of EZH2 expression was determined by Western blotting and immunohistochemical staining. We demonstrated the thickness of vascular remodeling by HE staining. JASPAR was used to predict transcription factors that could affect EZH2. Chromatin immunoprecipitation was used to substantiate the DNAprotein interactions. Promoter luciferase assays were performed to demonstrate the activity of the transcription factors. RESULTS: We found that in vivo, AAC significantly reduced EZH2 protein levels in the thoracic aorta. Smooth muscle-specific overexpression of EZH2 was sufficient to attenuate the AAC-induced reduction in trimethylation of Lys-27 in histone 3 and thickening of the arterial media. Administration of GSK-J4 (an inhibitor of H3K27me3 demethylase) induced the same effects. In addition, we found that mechanical stretch regulated the expression of EZH2 through the Yes-associated protein (YAP)- transcriptional factor TEA domain 1 (TEAD) pathway. TEAD1 bound directly to the promoter of EZH2, and blocking the YAP-TEAD1 interaction inhibited EZH2 downregulation due to mechanical stretch. CONCLUSION: This study reveals that mechanical stretch downregulates EZH2 through the YAP-TEAD1 pathway, thereby aggravating smooth muscle cell apoptosis and vascular remodeling.

Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus.

OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Dickkopf1 (Dkk1) Alleviates Vascular Calcification by Regulating the Degradation of Phospholipase D1 (PLD1).

Vascular calcification (VC) is a significant risk factor for cardiovascular mortality and morbidity in patients with atherosclerosis (AS), chronic kidney disease, and diabetes. Dickkopf1 (Dkk1) is a multifunctional secreted glycoprotein that has been explored as a novel potential antitumor target. Recently, Dkk1 was shown to be closely associated with AS development. However, the role of Dkk1 in VC remains elusive. In this study, we explored the role and molecular mechanisms of Dkk1 in VC based on a smooth muscle-specific Dkk1-knockout (Dkk1SMKO) mouse model. Our data indicated that Dkk1 expression was decreased under calcifying conditions and that Dkk1 overexpression alleviated high phosphate-induced vascular calcification. In vivo, smooth muscle Dkk1-specific knockout aggravated vascular calcification in mice. However, phospholipase D1 (PLD1) overexpression partially weakened the protective effect of Dkk1 against vascular calcification. Mechanistically, Dkk1 slowed vascular calcification by promoting the degradation of PLD1 via the regulating autophagosome formation and maturation. In conclusion, we found that Dkk1 could alleviate vascular calcification by regulating the degradation of PLD1.

Metabolic enzyme gene polymorphisms predict the effects of antioxidant treatment on idiopathic male infertility.

To explore the relationship between genetic polymorphisms of metabolic enzymes such as CYP1A1, CYP2D6, GSTM1, GSTT1, and GSTP1 and idiopathic male infertility. By observing the efficacy of antioxidants in the treatment of idiopathic male infertility, the effect of metabolic enzyme gene polymorphisms on antioxidant therapy in patients with idiopathic male infertility was prospectively studied. This case-control study included 310 men with idiopathic infertility and 170 healthy controls. The cytochrome P450 1A1 (CYP1A1), cytochrome P450 2D6 (CYP2D6), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) genotypes in peripheral blood samples were analyzed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). The idiopathic male infertility group was treated with vitamin C, vitamin E, and coenzyme Q10 for 3 months and followed up for 6 months. GSTM1(-), GSTT1(-), and GSTM1/T1(-/-) in the idiopathic male infertility groups were more common than those in the control group. The sperm concentration, motility, viability, mitochondrial membrane potential (MMP), and seminal plasma total antioxidant capacity (T-AOC) level in patients with GSTM1(-), GSTT1(-), and GSTM1/T1(-/-) were lower than those in wild-type carriers, and the sperm DNA fragmentation index (DFI), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and malondialdehyde (MDA) and nitric oxide (NO) levels were higher. Therefore, oxidative damage may play an important role in the occurrence and development of idiopathic male infertility, but antioxidant therapy is not effective in male infertility patients with GSTM1 and GSTT1 gene deletions.

Hepatic protective effects of Shenling Baizhu powder, a herbal compound, against inflammatory damage via TLR4/NLRP3 signalling pathway in rats with nonalcoholic fatty liver disease.

OBJECTIVE: High-fat diet (HFD) and inflammation are two key contributors to nonalcoholic fatty liver disease (NAFLD). Shenling Baizhu powder (SLBZP), a classical herbal compound, has been successfully used to alleviate NAFLD. However, its specific mechanisms are not fully understood. In this study, we assessed the anti-NAFLD effect of SLBZP in vivo. METHODS: Rats were fed an HFD with or without SLBZP or with probiotics. At the end of week 16, an echo magnetic resonance imaging (EchoMRI) body composition analyser was used to quantitatively analyse body composition; a micro-computed tomography (micro-CT) imaging system was used to evaluate whole body and liver fat; and the Moor full-field laser perfusion imager 2 was used to assess liver microcirculation, after which, all rats were sacrificed. Then, biochemical indicators in the blood and the ultrastructure of rat livers were evaluated. Protein expression related to the liver Toll-like receptor 4 (TLR4)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) signalling pathway was assessed using Western blot analysis. Further, high-throughput screening of 29 related inflammatory factors in liver tissue was performed using a cytokine array. RESULTS: SLBZP supplementation reduced body weight, serum free fatty acid, and insulin resistance index (P < 0.05). It also ameliorated liver microcirculation and ultrastructural abnormalities. EchoMRI and micro-CT quantitative analyses showed that treatment with SLBZP reduced fat mass and visceral fat (P < 0.05 and P < 0.01, respectively). In addition, SLBZP decreased the expression of lipopolysaccharide (LPS)-activated TLR4/NLRP3 signalling pathway-related proteins and altered the expression levels of some inflammatory cytokines in liver tissues. CONCLUSION: SLBZP can inhibit NLRP3 inflammasome activation and interleukin-1ß release by suppressing LPS-induced TLR4 expression in rats with HFD-induced NAFLD. Thus, SLBZP may be beneficial for the prevention and treatment of inflammatory damage and associated diseases.

MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model.

Sterile-20-like mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is expressed in endothelial cells and activates inflammatory vascular damage. Endothelial cells are important components of the blood-brain barrier. To investigate whether MAP4K4 plays a role in the pathophysiology of subarachnoid hemorrhage, we evaluated the time-course expression of MAP4K4 after subarachnoid hemorrhage. A subarachnoid hemorrhage model was established using the intravascular perforation method. The model mice were assigned to four groups: MAP4K4 recombinant protein, scramble small interfering RNA, and MAP4K4 small interfering RNA were delivered by intracerebroventricular injection, while PF-06260933, a small-molecule inhibitor of MAP4K4, was administrated orally. Neurological score assessments, brain water assessments, Evans blue extravasation, immunofluorescence, western blot assay, and gelatin zymography were performed to analyze neurological outcomes and mechanisms of vascular damage. MAP4K4 expression was elevated in the cortex at 24 hours after subarachnoid hemorrhage, and colocalized with endothelial markers. MAP4K4 recombinant protein aggravated neurological impairment, brain edema, and blood-brain barrier damage; upregulated the expression of phosphorylated nuclear factor kappa B (p-p65) and matrix metalloproteinase 9 (MMP9); and degraded tight junction proteins (ZO-1 and claudin 5). Injection with MAP4K4 small interfering RNA reversed these effects. Furthermore, administration of the MAP4K4 inhibitor PF-06260933 reduced blood-brain barrier damage in mice, promoted the recovery of neurological function, and reduced p-p65 and MMP9 protein expression. Taken together, the results further illustrate that MAP4K4 causes early blood-brain barrier damage after subarachnoid hemorrhage. The mechanism can be confirmed by inhibiting the MAP4K4/NF-κB/MMP9 pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of General Hospital of Northern Theater Command (No. 2018002) on January 15, 2018.

Conversion ratio of tacrolimus switching from intravenous infusion to oral administration after lung transplantation.

BACKGROUND: To investigate the conversion ratio of tacrolimus switching from intravenous infusion to oral administration in patients after lung transplantation. METHODS: We retrospectively recruited patients received lung transplantation in the First Affiliated Hospital of Guangzhou Medical Hospital from January 2015 to June 2019. The blood concentration of tacrolimus administrated through intravenous infusion and oral administration were collected. The blood concentration, concentration/dose ratio (C/D), and (C/Dpo)/(C/Div) ratio were analyzed to explore the conversion ratio of tacrolimus switching from intravenous infusion to oral administration, as combined medication of tacrolimus and caspofungin were used. RESULTS: The concentration of intravenously administered tacrolimus was significantly higher than that of oral administration; the C/D ratio of intravenously administrated tacrolimus (C/Div) was significantly higher than that of the oral administration (C/Dpo). There was a significant correlation between C/Dpo and C/Div (R2 =0.774, P<0.001). The conversion ratio of tacrolimus from intravenous administration to oral administration was 1:7.4, as combined medication of tacrolimus and caspofungin were used. CONCLUSIONS: The conversion ratio of tacrolimus switching from intravenous to oral administration is 1:7.4 in the combination treatment of tacrolimus and caspofungin after lung transplantation.

[Systematic review and screening of basic Chinese herbs for traditional Chinese medicine compounds combined with levodopa medicine in treatment of Parkinson's disease].

To systematically evaluate the efficacy of traditional Chinese medicine(TCM) compounds combined with levodopa medicine in the treatment of Parkinson's disease(PD), and screen basic herbs to provide certain evidence-based medical proof and program for better guidance on clinical drug use. Six databases were searched to screen out the randomized controlled trial on the TCM compounds combined with levodopa medicine in the treatment of PD. Literature quality of the included studies was evaluated by improved Jadad rating scale, and the Meta-analysis was performed by RevMan 5.3 software. After the data of the basic TCM compounds involved were sorted out, the strong association rules were found by using Apriori algorithm of SPSS Modeler 18.0 software, and then the basic herbs for the treatment of PD could be picked out. A total of 20 studies were eventually included, involving 1 784 patients. Ten studies were of high-quality literature, Jadad score≥4 points. Meta-analysis showed that efficacy of TCM combined with levodopa medicine was better than levodopa medicine alone in lowering Unified Parkinson's Disease Rating Scale(UPDRS) score: UPDRS Ⅰ(MD=-0.43, 95%CI[-0.62,-0.24], P<0.000 1), UPDRS Ⅱ(MD=-2.72, 95%CI[-3.24,-2.21], P<0.000 01), UPDRS Ⅲ(MD =-1.97, 95%CI[-2.69,-1.25], P<0.000 01), UPDRS Ⅳ(MD=-0.28, 95%CI[-0.46,-0.11], P=0.002). And the improvement in UPDRS score reduction rate of TCM combined with levodopa medicine was better than that in levodopa medicine alone: effective rate(OR=4.81, 95%CI[3.50, 6.62], P<0.000 01). Data mining results showed that the basic prescription for treating PD consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Gastrodiae Rhizoma in general. According to each part of UPDRS, the basic prescription for treating mentation, behavior and mood(UPDRS Ⅰ) consists of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Among which Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle might have unique efficacy. The basic prescriptions for treating UPDRS Ⅱ and UPDRS Ⅲ consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata, or Chuanxiong Rhizoma-Angelicae Sinensis Radix(two drug combinations). However, in the treatment of UPDRS Ⅳ, the drugs were scattered. But due to the limitations in the quantity and quality of clinical studies, the results obtained still need further research and clinical confirmation of its efficacy.

Depth-dependent ratcheting strains of young and adult articular cartilages by experiments and predictions.

BACKGROUND: Ratcheting strain is produced due to the repeated accumulation of compressive strain in cartilage and may be a precursor to osteoarthritis. The aim of this study was to investigate the ratcheting behaviors of young and adult articular cartilages under cyclic compression by experiments and theoretical predictions. METHODS: A series of uniaxial cyclic compression tests were conducted for young and adult cartilage, and the effects of different loading conditions on their ratcheting behaviors were probed. A theoretical ratcheting model was constructed and applied to predict the ratcheting strains of young and adult cartilages with different loading conditions. RESULTS: Ratcheting strains of young and adult cartilages rapidly increased at the initial stage, followed by a slower increase in subsequent stages. The strain accumulation value and its rate for young cartilage were greater than them for adult cartilage. The ratcheting strains of the two groups of cartilage samples decreased with increasing stress rate, while they increased with increasing stress amplitude. As the stress amplitude increased, the gap between the ratcheting strains of young and adult cartilages increased gradually. The ratcheting strains of young and adult cartilages decreased along the cartilage depth from the surface to the deep layer. The ratcheting strains of different layers increased with the compressive cycle, and the difference among the three layers was noticeable. Additionally, the theoretical predictions agreed with the experimental data. CONCLUSIONS: Overall, the ratcheting behavior of articular cartilage is affected by the degree of articular cartilage maturation.

CDC20 and its downstream genes: potential prognosis factors of osteosarcoma.

BACKGROUND: We investigated the microarray data GSE42352 to identify genes that can be used as prognosis factors in osteosarcoma. METHODS: Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of Cytoscape ClueGo were used in verifying the function of different genes. Realtime-PCR were used to confirm the microarray results. 83 patient samples were collected and underwent Kaplan-Meier survival analysis and multivariate analysis to predict the prospect of genes using as prognosis factors. RESULTS: After analyzing the microarray data GSE42352, mitosis metaphase to anaphase-related genes CDC20, securin, cyclin A2 and cyclin B2 were found to be overexpressed in osteosarcoma cell lines. Kaplan-Meier survival analysis showed that overexpression of these genes can predict poor prognosis outcomes in osteosarcoma patients. Furthermore, any combination of the four genes seems to be more effective in predicting osteosarcoma outcomes than any of these genes alone. CONCLUSIONS: CDC20 and its downstream substracts securin, cyclin A2 and cyclin B2 are good factors that can predict prognosis outcomes in osteosarcoma. Any two combination of these four genes are more effective to be used as osteosarcoma prognosis factors.

A cost-consequence analysis of parecoxib and opioids vs opioids alone for postoperative pain: Chinese perspective.

PURPOSE: The use of parecoxib plus opioids for postoperative analgesia in noncardiac surgical patients seems to be cost-saving in Europe due to a reduction in opioid use and opioid-related adverse events. Given the lack of information on postoperative analgesic use in Asia, this study assessed the economic consequences of the addition of parecoxib to opioids vs opioids alone to treat postsurgical pain in China. METHODS: A cost-consequence economic evaluation assessed direct medical costs related to opioid-related clinically meaningful events (CMEs) utilizing dosing information and reported frequency of events from a Phase III, randomized, double-blind, global clinical trial (PARA-0505-069) of parecoxib plus opioids vs opioids alone for 3 days following major orthopedic, abdominal, gynecologic, or noncardiac thoracic surgery requiring general or regional anesthesia. The cost of CMEs was calculated using information on resource utilization and unit costs provided by a panel of clinical experts in China. Sensitivity analyses were performed to test the robustness of the results. RESULTS: Patients treated with parecoxib plus opioids reported fewer CMEs (mean 0.62 vs 1.04 events per patient [P<0.0001]) compared with opioids alone for the 3-day postoperative period. This suggested a potential savings of 356 Chinese yuan (¥) per patient over the 3 days (total cost of ¥1,418 for parecoxib plus opioids vs ¥1,774 with opioid use alone). CONCLUSION: Fewer CMEs with parecoxib plus opioids suggest a reduction in medical resource utilization and reduced costs compared to opioids alone when modeling analgesic use in non-cardiac surgery patients in China.

ACTL6A interacts with p53 in acute promyelocytic leukemia cell lines to affect differentiation via the Sox2/Notch1 signaling pathway.

Actin-like 6A (ACTL6A), a component of BAF chromatin remodeling complexes, is important for cell differentiation. Nevertheless, its role and mechanism in acute promyelocytic leukemia (APL) has not been reported. To identify the genes that may participate in the development of APL, we analyzed data from an APL cDNA microarray (GSE12662) in the NCBI database, and found that ACTL6A was up-regulated in APL patients. Subsequently, we investigated the function and mechanisms of ACTL6A in myeloid cell development. The expression of ACTL6A was gradually decreased during granulocytic differentiation in all-trans retinoic acid-treated NB4 and HL-60 cells, and phorbol myristate acetate-treated HL-60 cells. We also found that knockdown of ACTL6A promoted differentiation in NB4 and HL-60 cells, and decreased the levels of Sox2 and Notch1. Mechanistically, ACTL6A interacted with and was co-localized with Sox2 and p53. Meanwhile, CBL0137, an activator of p53, decreased the expression of ACTL6A and promoted differentiation in NB4 and HL-60 cells. These findings suggest that the inhibition of ACTL6A promotes differentiation via the Sox2 and Notch1 signaling pathways. Furthermore, the differentiation promoted by inhibiting ACTL6A could be regulated by p53 via its physical interaction with ACTL6A.

Efficacy of common salvage chemotherapy regimens in patients with refractory or relapsed acute myeloid leukemia: A retrospective cohort study.

To assess treatment response and overall survival (OS) in refractory or relapsed acute myeloid leukemia (R/R AML) patients treated by different common salvage chemotherapy regimens.Medical records data from 142 R/R AML patients were reviewed in this retrospective study. Patients were treated with regimens based on the following drugs: cytarabine, granulocyte colony-stimulating factor (G-CSF), and fludarabine (FLAG) (n = 46); cytarabine and G-CSF in addition to aclarubicin or daunorubicin (CAG/DAG) (n = 30); cytarabine, G-CSF, and cladribine (CLAG) (n = 27); cytarabine, etoposide, and mitoxantrone (MEA) (n = 17); cytarabine plus idarubicin, daunorubicin, or mitoxantrone (IA/DA/MA) (n = 12); and homoharringtonine, cytarabine, and aclarubicin or daunorubicin (HAA/HAD) (n = 10).A total of 43 (35.2%) patients achieved complete remission (CR), 60 (49.2%) patients achieved overall remission rate (ORR), and 18 (14.8%) patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR. Median OS was 8.0 (95% CI 6.6-9.4) months with a 1-year OS rate of (29.9 ±â€Š3.9)% and 3-year OS rate of (11.1 ±â€Š3.6)%. No difference of CR (P = .621), ORR (P = .385), and allo-HSCT (P = .537) achievement was observed among different chemotherapy regimens. Interestingly, we observed that the CLAG-based regimen did not affect CR (P = .165), while it achieved a numerically higher ORR (P = .093) and was an independent factor for prolonged OS (P = .016). No other regimens were determined to be correlated with CR, ORR, or OS.FLAG-, CAG/DAG-, CLAG-, MEA-, IA/DA/MA- and HAA/HAD-based regimens were found to achieve similar CR rates, while the CLAG-based regimen achieved numerically higher ORR rates and significant favorable OS. Therefore, CLAG-based regimens should be a prioritized treatment option for R/R AML patients.

Asymmetric Total Synthesis of Lancifodilactone G Acetate. 1. Diastereoselective Synthesis of CDEFGH Ring System.

The stereoselective construction of the CDEFGH ring system of lancifodilactone G is described. The key steps in this synthesis are (i) ring-closing metathesis for formation of the oxa-bridged eight-membered ring; (ii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; and (iii) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G.

Asymmetric Total Synthesis of Lancifodilactone G Acetate. 2. Final Phase and Completion of the Total Synthesis.

The asymmetric total synthesis of lancifodilactone G acetate was accomplished in 28 steps. The key steps in this synthesis include (i) an asymmetric Diels-Alder reaction for formation of the scaffold of the BC ring; (ii) an intramolecular ring-closing metathesis reaction for the formation of the trisubstituted cyclooctene using a Hoveyda-Grubbs II catalyst; (iii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; (iv) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G; and (v) a Dieckmann-type condensation reaction for installation of the A ring. The strategy and chemistry developed for the total synthesis will be useful in the synthesis of other natural products and complex molecules.

Effects of placebo-controlled insulin-sensitizing drugs on hormonal parameters in polycystic ovary syndrome patients: A network meta-analysis.

This network meta-analysis was conducted to compare effects of different placebo-controlled insulin-sensitizing drugs, including metformin, pioglitazone, rosiglitazone, and troglitazone on hormonal parameters in polycystic ovary syndrome (PCOS) patients. We searched PubMed, EMBASE, and Cochrane Library databases from their inception to July 2017. Randomized controlled trials (RCTs) met our inclusion criteria were included. We combined direct and indirect evidences to evaluate weighted mean difference (WMD) value and draw surface under the cumulative ranking curve (SUCRA). Totally 28 eligible RCTs were enrolled. The network meta-analysis results indicated that: Compared with placebo, patients treated with pioglitazone had relatively higher sex-hormone-binding globulin (SHBG) (nmol/L) level (WMD = 6.65, 95%CI = 0.57-12.98), patients treated with metformin had comparatively lower total testosterone (TT) (ng/mL) level (WMD = -0.20, 95%CI = -0.39 to -0.02); Compared with rosiglitazone, patients treated with metformin had relatively higher estradiol (E2 ) (pg/mL) level (WMD = 47.91, 95%CI = 11.44-85.55). However, there were no statistical significance among the placebo-controlled insulin-sensitizing drugs in follicle stimulating hormone (FSH) (IU/L), luteinizing hormone (LH) (IU/L), dehydroepiandrostrone-sulphate (DHEAS) (µg/dL), free testosterone (FT) (pg/mL) and androstenedione (ng/mL). The results of cluster analysis showed that rosiglitazone may be the best drug for PCOS patients regarding to DHEAS, TT, FSH, and LH, metformin may be the best drug for PCOS patients as for E2 , FT, and androstenedione. Rosiglitazone had the best effect on PCOS patients in terms of DHEAS, TT, FSH, and LH, metformin had the best effect on PCOS patients for E2 , FT, and androstenedione.