Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.

Male vitellogenin regulates gametogenesis through a testis-enriched big protein in Chrysopa pallens.

In insects, vitellogenin (Vg) is generally viewed as a female-specific protein. Its primary function is to supply nutrition to developing embryos. Here, we reported Vg from the male adults of a natural predator, Chrysopa pallens. The male Vg was depleted by RNAi. Mating with Vg-deficient male downregulated female Vg expression, suppressed ovarian development and decreased reproductive output. Whole-organism transcriptome analysis after male Vg knockdown showed no differential expression of the known spermatogenesis-related regulators and seminal fluid protein genes, but a sharp downregulation of an unknown gene, which encodes a testis-enriched big protein (Vcsoo). Separate knockdown of male Vg and Vcsoo disturbed the assembly of spermatid cytoplasmic organelles in males and suppressed the expansion of ovary germarium in mated females. These results demonstrated that C. pallens male Vg signals through the downstream Vcsoo and regulates male and female reproduction.

[Study on mechanism of inhibiting proliferation of head and neck cancer cells by citral, active ingredient of lemon essential oil].

To explore the active substances exerting anti-tumour effect in lemon essential oil and the molecular mechanism inhibiting the proliferation of head and neck cancer cells SCC15 and CAL33, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay(MTT) was utilized to identify the active component inhibiting the proliferation of head and neck cancer cells, namely citral. The IC_(50) of citral inhibiting the proliferation of head and neck cancer cells and normal cells were also determined. In addition, a 5-ethynyl-2'-deoxyuridine(EdU) staining assay was used to detect the effect of citral on the proliferation rate of head and neck cancer cells, and a colony formation assay was used to detect the effect of citral on tumor sphere formation of head and neck cancer cells in vitro. The cell cycle arrest and apoptosis induction of head and neck cancer cells by citral were evaluated by flow cytometry, and Western blot was used to detect the effect of citral on the expression levels of cell cycle-and apoptosis-related proteins in head and neck cancer cells. The findings indicated that citral could effectively inhibit the proliferation and growth of head and neck cancer cells, with anti-tumor activity, and its half inhibitory concentrations for CAL33 and SCC15 were 54.78 and 25.23 µg·mL~(-1), respectively. Furthermore, citral arrested cell cycle at G_2/M phase by down-regulating cell cycle-related proteins such as S-phase kinase associated protein 2(SKP2), C-MYC, cyclin dependent kinase 1(CDK1), and cyclin B. Moreover, citral increased the cysteinyl aspartate-specific proteinase-3(caspase-3), cysteinyl aspartate-specific proteinase-9(caspase-9), and cleaved poly ADP-ribose polymerase(PARP). It up-regulated the level of autophagy-related proteins including microtubule associated protein 1 light chain 3B(LC3B), sequestosome 1(P62/SQSTM1), autophagy effector protein Beclin1(Beclin1), and lysosome-associate membrane protein 1(LAMP1), suggesting that citral could effectively trigger cell apoptosis and cell autophagy in head and neck cancer cells. Furthermore, the dual-tagged plasmid system mCherry-GFP-LC3 was used, and it was found that citral impeded the fusion of autophagosomes and lysosomes, leading to autophagic flux blockage. Collectively, our findings reveal that the main active anti-proliferation component of lemon essential oil is citral, and this component has a significant inhibitory effect on head and neck cancer cells. Its underlying molecular mechanism is that citral induces apoptosis and autophagy by cell cycle arrest and ultimately inhibits cell proliferation.

Dynamic tripartite construct of interregional engram circuits underlies forgetting of extinction memory.

Fear extinction allows for adaptive control of learned fear responses but often fails, resulting in a renewal or spontaneous recovery of the extinguished fear, i.e., forgetting of the extinction memory readily occurs. Using an activity-dependent neuronal labeling strategy, we demonstrate that engram neurons for fear extinction memory are dynamically positioned in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC), which constitute an engram construct in the term of directional engram synaptic connectivity from the BLA or vHPC to mPFC, but not that in the opposite direction, for retrieval of extinction memory. Fear renewal or spontaneous recovery switches the extinction engram construct from an accessible to inaccessible state, whereas additional extinction learning or optogenetic induction of long-term potentiation restores the directional engram connectivity and prevents the return of fear. Thus, the plasticity of engram construct underlies forgetting of extinction memory.

Stretchable Semi-Interpenetrating Carboxymethyl Guar Gum-Based Composite Hydrogel for Moisture-Proof Wearable Strain Sensor.

Wearable strain sensors of conductive hydrogels have very broad application prospects in electronic skins and human-machine interfaces. However, conductive hydrogels suffer from unstable signal transmission due to environmental humidity and inherent shortcomings of their materials. Herein, we introduce a novel moisture-proof conductive hydrogel with high toughness (2.89 MJ m-3), mechanical strength (1.00 MPa), and high moisture-proof sensing performance by using dopamine-functionalized gold nanoparticles as conductive fillers into carboxymethyl guar gum and acrylamide. Moreover, the hydrogel can realize real-time monitoring of major and subtle human movements with good sensitivity and repeatability. In addition, the hydrogel-assembled strain sensor exhibits stable sensing signals after being left for 1 h, and the relative resistance change rate under different strains (25-300%) shows no obvious noise signal up to 99% relative humidity. Notably, the wearable strain sensing is suitable for wearable sensor devices with high relative humidity.

Yolk Sac Tumor Originating From Cervical Adenocarcinoma: A Case Predominated by Enteroblastic Differentiation.

The fetal gut-like phenotype can be found in yolk sac tumors and adenocarcinomas with enteroblastic differentiation (AEBDs). We report a cervical yolk sac tumor in a 44-yr-old woman. The tumor has similar morphology, immunophenotype, and molecular features to the AEBD of the digestive system. The tumor showed a glandular-predominant growth pattern, composed of columnar cells with clear glycogen-rich cytoplasm. The microcystic/reticular architecture or Schiller-Duval bodies were not found in the tumor. Immunohistochemically, the tumor cells were positive for p16, glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), CDX-2, and p53. TP53 mutation was identified by next-generation sequencing, and human papillomavirus (HPV) 35 was detected by HPV DNA polymerase chain reaction. In the present case, the adenocarcinoma cells in the superficial cervical glandular epithelium and the nonclear glandular components proved the existence of somatic components. The positivity of p16 and HPV also supports that the present case originates from an HPV-associated adenocarcinoma. The yolk sac tumor should be thought of as "germ cell differentiation" from a somatic carcinoma. This kind of yolk sac tumor arising from somatic-type adenocarcinoma in the female genital tract may be the counterpart of AEBD in the digestive tracts and adenocarcinomas with fetal gut-like morphology in other organs. The tumor might be more aggressive than conventional adenocarcinoma, pathologists should highlight the existence of the enteroblastic component in the pathologic report.

Primary membranous nephropathy in two siblings with one combined with anti-glomerular basement membrane disease: a case report.

BACKGROUND: The phospholipase A2 receptor (PLA2R) associated with membranous nephropathy (MN) is an organ-specific autoimmune disease associated with PLA2R and human leukocyte antigen (HLA) genes. Familial PLA2R-related MN is rarely reported. The combination of anti-GBM disease and MN has been well documented, though the mechanism behind it remains unclear. CASE PRESENTATION: We describe two siblings diagnosed with pathology-confirmed PLA2R-related MN 1 year apart. And one of the two siblings developed an anti-GBM disease. The high-resolution HLA typing showed identical alleles in both siblings, specifically heterozygotes of DRB1*15:01/*03:01. CONCLUSION: We describe a familial case of PLA2R-related MN supporting the role of genetic factors that HLA-DRB1*15:01 and DRB1*03:01 predispose patients in the development of PLA2R-related MN in the Han Chinese population. The combination of MN and anti-GBM disease may also partially be associated with the same susceptible HLA allele DRB1*15:01.

Inulin-type oligosaccharides of Morinda officinalis exerted antidepressant effects by reducing hippocampal inflammation.

Neuroinflammation contributes to the pathogenesis of depression. Inulin-type oligosaccharides of Morinda officinalis (IOMO) exert antidepressant-like effects in rodents and patients with depression, while the underlying mechanisms remain unclear. This study used chronic restraint stress (CRS) and lipopolysaccharide (LPS) to induce depression-like behaviors in mice. Western blotting and ELISA analysis were used to investigate the effects of IOMO on inflammatory cytokine levels. Immunofluorescence analysis was used to investigate the effects of IOMO on hippocampal NLRP3 inflammasome and microglial cells. The results suggested that 6 weeks of CRS induced significant depression-like behaviors based on the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST), which were accompanied by increases in the expression of IL-6 and the activation of hippocampal microglial cells. Chronic treatment with IOMO (25 mg/kg, i.g.) for 28 days significantly reversed these depression-like behaviors and inhibited the activation of microglial cells. Furthermore, LPS (0.5 mg/kg, i.p.) also significantly induced depression-like behaviors in the TST, FST, and novelty-suppressed feeding test (NSFT), as well as increased the expression of IL-1ß and caspase-1, and activated the microglial cells and the NLRP3 inflammasome in the hippocampus. Treatment with IOMO for 9 days significantly reversed these depression-like behaviors and normalized the LPS-induced activation of the microglial cells and NLRP3 inflammasome. Taken together, these results suggested that IOMO exerted antidepressant-like effects via hippocampal microglial NLRP3 inflammasome mediation followed by caspase-1 inhibition and the production of IL-1ß. These findings provide a basis for developing new antidepressants targeting the microglial NLRP3 inflammasome.

Topographic Differences in Superficial Macular Vessel Density in Eyes with Early Primary Open-Angle Glaucoma and Normal Tension Glaucoma.

INTRODUCTION: The aim of the study was to compare macular vascular microcirculation in early primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), and normal subjects. METHODS: 99 patients with early glaucoma (99 eyes: 60 POAG and 39 NTG) and 78 normal subjects were included. All subjects underwent optical coherence tomography angiography scan at 6 × 6 mm macular area. Macular vessel density (VD) and perfusion density (PD) and 9 sectors were compared between the controls, POAG, and NTG groups. Linear regression analysis was used to investigate the relationship between VD and other variables including macular PD, signal strength (SS), and mean macular ganglion cell-inner plexiform layer (mGCIPL) thickness. RESULTS: Significant losses in total area of VD and PD were detected in POAG and NTG groups compared to the controls (all p < 0.01). There were no significant differences in all inner sectors of macular VD and PD between POAG and controls (all p > 0.05). Except for outer-nasal sector, all other outer sectors of macular VD and PD were significantly lower in POAG than in the controls (all p < 0.01). The inferior-inner sector and all outer sectors of VD and PD were significantly lower in NTG than in the controls (all p < 0.01). Macular VD was significantly correlated with macular PD (r = 0.99, p < 0.001), SS (r = 0.60, p < 0.001), and mGCIPL thickness (r = 0.51, p < 0.001). CONCLUSIONS: Macular microcirculation declined significantly in early POAG and NTG patients. Macular microcirculation loss in the NTG group was more central and nasal compared with that in the POAG group. A decrease in macular VD was correlated with lower macular PD, lower SS, and thinner mGCIPL thickness.

Isolation and Characterization of trans-p-Hydroxycinnamoyl Meroterpenoids from Ganoderma sinensis.

Zizhines V, W, Y, Z, (±)-zizhines X, and Z1-Z3, and (±)-ganosinensol L, thirteen new compounds including four pairs of enantiomers and a known compound (-)-ganosinensol L, were isolated from the fruiting bodies of Ganoderma sinensis. Their structures were identified by spectroscopic, computational methods, and CD (circular dichroism spectroscopy) comparisons. Zizhines V-Z and Z1-Z3 are meroterpenoids consisting of the phenolic and the terpenoidal parts. All the compounds except zizhine Z3 bear a common trans-p-hydroxycinnamoyl group. Biological evaluation shows that (-)-zizhine Z1 inhibits cell migration in the MDA-MB-231 cell lines. The present study discloses the chemical profiling of G. sinensis and paves the way for its development as functional products to benefit chronic disorders.

Gastroduodenal artery disconnection during liver transplantation decreases non-anastomotic stricture incidence.

BACKGROUND: The hepatic artery is the only blood source nourishing the biliary duct and associated with biliary complication after liver transplantation (LT). Gastroduodenal artery (GDA) disconnection increased proper hepatic artery flow. Whether this procedure attenuates biliary non-anastomotic stricture (NAS) is not clear. METHODS: A total of 241 patients with LT were retrospectively analyzed. The patients were divided into the GDA disconnection (GDA-) and GDA preservation (GDA+) groups. Propensity score matching (PSM) was administrated to reduce bias. Logistic regression was conducted to analyze risk factors for biliary NAS before and after PSM. Postoperative complications were compared. Kaplan-Meier survival analysis and log-rank tests were performed to compare overall survival. RESULTS: In all, 99 patients (41.1%) underwent GDA disconnection, and 49 (20.3%) developed NAS. Multivariate logistic regression revealed that GDA preservation (OR = 2.24, 95% CI: 1.11-4.53; P = 0.025) and model for end-stage liver disease (MELD) score > 15 (OR = 2.14, 95% CI: 1.12-4.11; P = 0.022) were risk factors for biliary NAS. PSM provided 66 pairs using 1:2 matching method, including 66 GDA disconnection and 99 GDA preservation patients. Multivariate logistic regression after PSM also showed that GDA preservation (OR = 3.15, 95% CI: 1.26-7.89; P = 0.014) and MELD score > 15 (OR = 2.41, 95% CI: 1.08-5.36; P = 0.031) were risk factors for NAS. When comparing complications between the two groups, GDA preservation was associated with a higher incidence of biliary NAS before and after PSM (P = 0.031 and 0.017, respectively). In contrast, other complications including early allograft dysfunction (P = 0.620), small-for-size graft syndrome (P = 0.441), abdominal hemorrhage (P = 1.000), major complications (Clavien-Dindo grade ≥ 3, P = 0.318), and overall survival (P = 0.088) were not significantly different between the two groups. CONCLUSIONS: GDA disconnection during LT ameliorates biliary NAS incidence and may be recommended for application in clinical practice.

Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways.

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.

Oxygen-Free Csp3-H Oxidation of Pyridin-2-yl-methanes to Pyridin-2-yl-methanones with Water by Copper Catalysis.

Aromatic ketones are important pharmaceutical intermediates, especially the pyridin-2-yl-methanone motifs. Thus, synthetic methods for these compounds have gained extensive attention in the last few years. Transition metals catalyze the oxidation of Csp3-H for the synthesis of aromatic ketones, which is arresting. Here, we describe an efficient copper-catalyzed synthesis of pyridin-2-yl-methanones from pyridin-2-yl-methanes through a direct Csp3-H oxidation approach with water under mild conditions. Pyridin-2-yl-methanes with aromatic rings, such as substituted benzene, thiophene, thiazole, pyridine, and triazine, undergo the reaction well to obtain the corresponding products in moderate to good yields. Several controlled experiments are operated for the mechanism exploration, indicating that water participates in the oxidation process, and it is the single oxygen source in this transformation. The current work provides new insights for water-involving oxidation reactions.

Gramella sediminis sp. nov., isolated from a tidal flat of the Yellow Sea.

A novel species of the genus Gramella, designated ASW11-100T, was isolated from a tidal flat sediment in the Yellow Sea, PR China. Phylogenetic analysis based on 16S rRNA gene sequences and single-copy orthologous clusters revealed that strain ASW11-100T belonged to the genus Gramella, and exhibited 16S rRNA gene sequence similarities of 98.9, 98.8 and 98.7 % to Gramella sabulilitoris HSMS-1T, Gramella sediminilitoris GHTF-27T and Gramella forsetii KT0803T, respectively. The genome of strain ASW11-100T harbours 2950 protein-coding genes and 105 carbohydrate-active enzymes including 38 glycoside hydrolases. Seventeen of the glycoside hydrolases are organized in five distinct polysaccharide utilization loci, which are predicted to involve in the degradation of starch, glucans, arabinoxylans, arabinomannan, arabinans and arabinogalactans. The genomic DNA G+C content was 37.3 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-100T and its closely related relatives were in ranges of 19.8-23.9% and 76.6-80.9 %, respectively. Cells of the isolate were Gram-negative, aerobic, non-flagellated and short rod-shaped. Carotenoid pigments were produced, but flexirubin-type pigments were absent. The major fatty acids (>10 %) were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c). The sole respiratory quinone was menaquinone-6 and the major polar lipid was phosphatidylethanolamine. Based on the above polyphasic evidence, strain ASW11-100T should be considered to represent a novel Gramella species, for which the name Gramella sediminis sp. nov. is proposed. The type strain is ASW11-100T (=KCTC 82502T=MCCC 1K05580T).

Influence of genetic polymorphisms in P2Y12 receptor signaling pathway on antiplatelet response to clopidogrel in coronary heart disease.

BACKGROUNDS: Remarkable interindividual variability in clopidogrel response is observed, genetic polymorphisms in P2RY12 and its signal pathway is supposed to affect clopidogrel response in CHD patients. METHODS: 539 CHD patients treated with clopidogrel were recruited. The platelet reaction index (PRI) indicated by VASP-P level were detected in 12-24 h after clopidogrel loading dose or within 5-7 days after initiation of maintain dose clopidogrel. A total of 13 SNPs in relevant genes were genotyped in sample A (239 CHD patients). The SNPs which have significant differences in PRI will be validated in another sample (sample B, 300 CHD patients). RESULTS: CYP2C19*2 increased the risk of clopidogrel resistance significantly. When CYP2C19*2 and CYP2C19*3 were considered, CYP2C19 loss of function (LOF) alleles were associated with more obviously increased the risk of clopidogrel resistance; P2RY12 rs6809699C > A polymorphism was also associated with increased risk of clopidogrel resistance (AA vs CC: P = 0.0398). This difference still existed after stratification by CYP2C19 genotypes. It was also validated in sample B. The association was also still significant even in the case of stratification by CYP2C19 genotypes in all patients (sample A + B). CONCLUSION: Our data suggest that P2RY12 rs6809699 is associated with clopidogrel resistance in CHD patients. Meanwhile, the rs6809699 AA genotype can increase on-treatment platelet activity independent of CYP2C19 LOF polymorphisms.

Salinimicrobium sediminilitoris sp. nov., Isolated from a Tidal Flat.

A Gram-negative, facultatively anaerobic, motile, and rod-shaped bacterium, designated ASW11-47 T, was isolated from a tidal flat sediment taken from the coast of Qingdao, PR China. Phylogenetic analysis of 16S rRNA gene sequence showed that strain ASW11-47 T belongs to the genus Salinimicrobium and is most closely related to Salinimicrobium terrae YIM-C338T (98.68% similarity). The length of draft genome is 3,594,457 bp, and DNA G + C content is 40.8 mol%. The values of average nucleotide identity and digital DNA-DNA hybridization between strain ASW11-47 T and closely related strains were in ranges of 75.9-85.9 and 19.7-31.5%, respectively. The major fatty acids (> 10%) were iso-C15:0 and iso-C17:0 3-OH. The predominant respiratory quinone was menaquinone-6 and the major polar lipid was phosphatidylethanolamine. On the basis of genotypic, phenotypic, and chemotaxonomic analysis, strain ASW11-47 T represents a novel species within the genus Salinimicrobium, for which the name Salinimicrobium sediminilitoris sp. nov. is proposed. The type strain is ASW11-47 T (= KCTC 82501 T = MCCC 1K05586T).

[Determination of Dichloromethane in Blood with Headspace Gas Chromatography and Gas Chromatography-Mass Spectrometry].

Objective: To establish a method for qualitative determination of dichloromethane (DCM) in blood by gas chromatography-mass spectrometry (GC-MS) and quantitative determination of DCM in blood by headspace gas chromatography (HS-GC), and to provide reliable support for forensic examination and analysis of poisoning or deaths caused by DCM. Methods: 0.5 mL blood sample was collected, added into headspace vial with chloroform as the internal standard, and processed by heating at 65 °C and evacuation treatment. The intermediate gas in the headspace vial was analyzed by GC-MS for qualitative validation of the method and by HS-GC for quantitative validation of the method. The method was then applied in forensic case analysis. Results: Qualitative validation of the examination method by GC-MS found that the chromatographic peak and mass spectral characteristic ions were specific in samples added with DCM, and that no interference was observed in the blank negative samples. The limit of detection (LOD) was 5 µg/mL. Quantitative method validation by HS-GC found that the chromatographic peak of DCM was well separated from those of eight other volatile compounds, with the resolution>1.5 in all cases; the lower limit of quantification (LOQ) was 20 µg/mL and good linearity was shown within the range of 20 and 1000 µg/mL, R>0.999; the intra-day test precision and inter-day test precision were good (relative standard deviation, or RSD<15% for both) and test accuracy was high (relative error, or δ<15%). With the method established in the study, DCM was detected successfully in the blood of two fatal cases caused by DCM poisoning, with the blood concentration being 470 µg/mL and 915 µg/mL, respectively. Conclusion: This method is shown to be a rapid, stable and accurate approach to the qualitative and quantitative forensic and toxicological analysis of DCM in blood in DCM poisoning cases or deaths caused by DCM.

[Content correlation of eight phenolic acids and flavonoids in different medicinal parts of PA-type Perilla germplasms].

In this study, 10 PA-type Perilla germplasms were selected to detect the content of two phenolic acids, i.e., rosmarinic acid(RA) and caffeic acid(CA), and six flavonoids, including scutellarin-7-O-diglucuronoside(SDG), luteolin-7-O-diglucuronoside(LDG), apigenin-7-O-diglucuronoside(ADG), scutellarin-7-O-glucuroside(SG), luteolin-7-O-glucuroside(LG), and apigenin-7-O-glucuroside(AG) in leaves, stems, and fruits. The total content of phenolic acids and flavonoids in leaves was 3.991-12.028 mg·g~(-1) and 12.309-25.071 mg·g~(-1), respectively, which was much higher than that in stems(0.586-2.015 mg·g~(-1) and 0.879-1.413 mg·g~(-1), respectively) and fruits(0.004-2.222 mg·g~(-1) and 0.651-1.936 mg·g~(-1), respectively). RA was detected in five fruit samples, and RA content between leaves and fruits showed a significant negative correlation in the other five samples. For flavonoids, only LG and LDG could be detected in stems, and SG and SDG were not detected in fruits, while other flavonoids were not detected in some samples. The content of total flavonoids and LG in leaves and fruits was significantly positively correlated, and the content of LG in stems and fruits was significantly positively correlated. In 10 stem samples, seven met the standard that the content of RA in the stem should be not less than 0.1% specified in the Chinese Pharmacopoeia(2020 edition). Only one fruit sample reached the standard of RA content in the fruit not less than 0.25% specified in the Chinese Pharmacopoeia.

[Effect of polydatin on the proliferation and apoptosis of THP-1 cells and the mechanism]. / 虎杖苷对THP-1ç»†èƒžå¢žæ®–åŠå‡‹äº¡çš„å½±å“åŠå ¶ä½œç”¨æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To explore the effect of polydatin on the proliferation and apoptosis of acute monocytic leukemia cell line THP-1 and the possible mechanism. METHODS: After THP-1 cells were treated with polydatin at gradient concentrations for 24 hours and 48 hours, their proliferation was determined by CCK-8 assay, and half maximal inhibitory concentration (IC50) was calculated. Logarithmically growing THP-1 cells were divided into two groups, a polydatin treatment group (treated with IC50 of polydatin) and a blank control group (treated without polydatin solution), and incubated for 48 hours. Cell apoptosis and cell cycle were measured by flow cytometry. The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins were measured by Western blotting. RESULTS: After treatment with polydatin, the proliferation of THP-1 cells was strongly inhibited, and the IC50 at 48 hours was 1 800 µmol/L. After treatment with 1 800 µmol/L polydatin solution for 48 hours, the apoptosis rate of THP-1 cells increased significantly compared with the blank control group (P<0.05). The cell cycle was arrested in the G0/G1 and S phases, with a significantly increased proportion of cells in the G0/G1 phase and a significantly decreased proportion of cells in the S phase, as compared with the blank control group (P<0.05). The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins decreased significantly compared with the blank control group (P<0.05). CONCLUSIONS: Polydatin can effectively inhibit the proliferation, block the cell cycle, and induce the apoptosis of THP-1 cells, which may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.

Common variation of the NSD1 gene is associated with susceptibility to Hirschsprung's disease in Chinese Han population.

BACKGROUND: Hirschsprung's disease (HSCR) is the most common congenital cause of intestinal obstruction in children. Sotos syndrome (SoS) is an overgrowth disorder with constipation and sometimes accompanied by HSCR. NSD1 gene mutation is the main cause of SoS. We aimed to investigate association of NSD1 common single nucleotide polymorphisms (SNPs) with HSCR susceptibility in Chinese Han population. METHOD: We genotyped 15 SNPs encompassing NSD1 gene region in 420 HSCR patients and 1665 controls on Fludigm EP1 platform. Association analysis was performed between cases and controls. RESULT: Rs244709 was the most associated SNP with HSCR susceptibility of the sample set (PAllelic = 9.69 × 10-5, OR = 1.37, 95% CI: 1.17-1.61). Gender stratification analysis revealed that NSD1 SNPs were associated with HSCR in males, but not in females. The nonsynonymous coding SNP rs28932178 in NSD1 exon 5 represented the most significant signal in males (PAllelic = 6.43 × 10-5, OR = 1.42, 95% CI: 1.20-1.69). The associated SNPs were expression quantitative trait loci (eQTLs) of nearby genes in multiple tissues. NSD1 expression levels were higher in aganglionic colon tissues than ganglionic tissues (P = 3.00 × 10-6). CONCLUSION: NSD1 variation conferred risk to HSCR in males, indicating SoS and HSCR may share common genetic factors. IMPACT: This is the first study to reveal that NSD1 variation conferred risk to Hirschsprung's disease susceptibility in males of Chinese Han population, indicating Sotos syndrome and Hirschsprung's disease may share some common genetic background. This study indicates more attention should be paid to the symptom of constipation in patients with Sotos syndrome. Our results raise questions about the role of NSD1 in the development of enteric nervous system and the pathogenesis of Hirschsprung's disease.