CGRP promotes osteogenic differentiation by regulating macrophage M2 polarization through HDAC6/AKAP12 signaling pathway.

Aim: To determine the mechanism of Calcitonin gene-related peptide (CGRP) in bone healing.Materials & methods: Alkaline phosphatase (ALP) activity and inflammatory-factor levels were detected using ELISA. Osteogenic differentiation was assessed using Alizarin red staining technique. The interaction between histone deacetylase 6 (HDAC6) and A-kinase anchoring protein 12 (AKAP12) was investigated through Co- immunoprecipitation.Results: CGRP treatment promoted rat bone marrow-derived macrophages (BMDMs) M2 polarization. CGRP facilitated osteogenic differentiation by enhancing M2 polarization of BMDMs. Mechanistically, CGRP promoted AKAP12 acetylation to activate the extracellular regulated protein kinases pathway by HDAC6 inhibition.Conclusion: CGRP promoted M2 polarization of rat BMDMs and facilitated osteogenic differentiation through the HDAC6/AKAP12/extracellular regulated protein kinases signaling pathway, thereby promoting bone healing.

[Box: see text].

Reassessment of EUS features in preoperative diagnosis of pancreatic serous cystic neoplasm: Lessons to avoid misdiagnosis.

OBJECTIVES: Pancreatic serous cystic neoplasm (SCN) is a benign cystic neoplasm that is likely to be surgically resected due to preoperative misdiagnosis or tentative diagnosis even using endoscopic ultrasonography (EUS). We aimed to analyze EUS findings of SCN associated with misdiagnosis. METHODS: Between January 2012 and September 2023, histologically confirmed pancreatic SCN were included and EUS features were reviewed. RESULTS: Overall, 294 patients with 300 surgically resected SCNs were included. The median age of the patients was 51 years and 75.9% were females. The lesions were predominantly located in the body/neck/tail of the pancreas (63.0%). The overall preoperative diagnostic rate of SCN was 36.3%, with the most common misdiagnosis being intraductal papillary mucinous neoplasm (IPMN) (31.3%), while 16.3% remained undefined. The preoperative diagnostic rate of SCN varied across different endosonographic morphologies, with oligocystic, macrocystic, microcystic, and solid patterns yielding rates of 12.8%, 37.9%, 76.5%, and 19.2%, respectively. Notably, the presence of central scar and vascularity improved the diagnostic accuracy and correctly identified 41.4% and 52.3% of the lesions. While mucus or pancreatic duct (PD) communication significantly increased the likelihood of misdiagnosis, particularly as IPMN. Multivariate analysis revealed a morphological pattern, mucin-producing signs, wall thickening, vascularity, and PD communication were independent factors related to preoperative misdiagnosis, with an overall accuracy of 82.3%. CONCLUSIONS: Preoperative diagnosis of SCN remains challenging. The microcystic pattern emerged as a reliable feature, while mucin-producing signs, including mural nodules, mucus, and PD communication, pose diagnostic pitfalls despite the presence of typical central scar or vascularity commonly in SCN.

A nitrous oxide/oxygen fixed mixture to reduce pain induced by the hypodermic injection: study protocol for a randomized, controlled trial.

BACKGROUND: Patients with hematological malignancies received multiple hypodermic injections of recombinant human granulocyte colony-stimulating factor. Procedural pain is one of the most common iatrogenic causes of pain in patients with hematological malignancies. It is also identified as the most commonly occurring problem in clinical care in the Department of Hematology and Oncology at Shenzhen University General Hospital. However, providing immediate relief from pain induced by hypodermic injection of recombinant human granulocyte colony-stimulating factor remains a major challenge. This trial aims to evaluate the safety and analgesic efficacy of a fixed nitrous oxide/oxygen mixture for patients with hematological malignancies and experiencing procedural pain caused by hypodermic injection of recombinant human granulocyte colony-stimulating factor in the department. METHODS: The nitrous oxide/oxygen study is a single-center, randomized, double-blind, placebo-controlled trial involving patients with hematological malignancies who require hypodermic injections of recombinant human granulocyte colony-stimulating factor for treatment. This trial was conducted in the Hematology and Oncology Department of Shenzhen University General Hospital. A total of 54 eligible patients were randomly allocated to either the fixed nitrous oxide/oxygen mixture group (n = 36) or the oxygen group (n = 18). Neither the investigators nor the patients known about the randomization list and the nature of the gas mixture in each cylinder. Outcomes were monitored at the baseline (T0), immediately after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T1), and 5 min after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T2) for each group. The primary outcome measure was the score in the numerical rating scale corresponding to the highest level of pain experienced during hypodermic injection of recombinant human granulocyte colony-stimulating factor. Secondary outcomes included the fear of pain, anxiety score, four physiological parameters, adverse effects, total time of gas administration, satisfaction from both patients and nurses, and the acceptance of the patients. DISCUSSION: This study focused on the safety and analgesic efficacy during hypodermic injection of recombinant human granulocyte colony-stimulating factor procedure. Data on the feasibility and safety of nitrous oxide/oxygen therapy was provided if proven beneficial to patients with hematological malignancies during hypodermic injection of recombinant human granulocyte colony-stimulating factor and widely administered to patients with procedural pain in the department. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2200061507. Registered on June 27, 2022. http://www.chictr.org.cn/edit.aspx?pid=170573&htm=4.

Function analysis and characterisation of a novel chitinase, MdCht9, in Musca domestica.

Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.

Effect of leaves damaged by Dendrolimus punctatus and insect frass on soil priming effect.

Insect herbivory in the forest canopy leads to a large amount of damaged leaves and frass input to soil, with consequence on soil carbon cycle. However, the influence of damaged leaves and frass from insect canopy herbivory on the soil priming effect is unclear. We examined the effects of leaf litter, leaf damage caused by Dendrolimus punctatus, and insect frass on soil priming effect by using the 13C natural abundance technique. The results showed that the addition of leaf litter, damaged leaves, and frass significantly increased native soil organic carbon mineralization, producing a positive priming effect. Moreover, significant differences were observed among treatments. The accumulative priming effect induced by frass was the largest, followed by damaged leaves, and that of leaf litter was the smallest. The priming effect was positively correlated with total P, condensed tannin, total phenolic content, and the ratio of condensed tannin to P (condensed tannin/P), and negatively correlated with C/N, lignin/N, C/P, and lignin/P in the early stage of incubation. There was a significant negative correlation between the priming effect and lignin content in the later stage of incubation. Our results indicated that damaged leaves and frass increased the magnitude of positive priming effect, which was influenced by different factors at different incubation stages. Our results would strengthen the understanding in the effects of insect herbivory on soil carbon cycling in forests, and improve the accuracy of the assessment of its effects on forest carbon sink.

 Sinoseneciominshanicus (Asteraceae, Senecioneae), a new species from south-eastern Gansu and northern Sichuan, China.

Sinoseneciominshanicus (Asteraceae, Senecioneae), a new species from south-eastern Gansu (Wenxian and Zhugqu counties) and northern Sichuan (Pingwu county), China, is described and illustrated. This species is similar to S.rotundifolius, a species locally endemic to Songpan county in northern Sichuan, in having a scapigerous habit, orbicular leaves and solitary capitula, but differs by the presence (vs. absence) of stolons and by having thinner rhizomes (ca. 2 mm vs. more than 5 mm in diameter), stems proximally sparsely fulvous arachnoid or glabrescent (vs. densely sericeous-villous) and obscure (vs. conspicuous) main veins on adaxial surface of leaves. The chromosome number of the new species is reported to be 2n = 60. Colour photographs of living plants in the wild and a distribution map are provided for the new species and S.rotundifolius. The geographical distribution of S.rotundifolius is also corrected, with the previous record of this species from south-eastern Gansu (Wenxian county) actually referring to S.minshanicus.

Sinoseneciopingwuensis (Asteraceae, Senecioneae), a new species from northern Sichuan, China.

Sinoseneciopingwuensis (Asteraceae, Senecioneae), a new species from Pingwu county in northern Sichuan, China, is described and illustrated. This species is distinguished in Sinosenecio by having leathery, glabrous, ovate or ovate-oblong leaves often pinnately-veined and solitary capitula 2.3-4.3 cm in diameter, a unique character combination hitherto never recorded in the genus. Two floral micromorphological characters (configuration of filament collar of stamens and anther endothecial cell wall thickenings) and achene surface features of the new species are reported. Color photographs of living plants and a distribution map are also provided for the new species.

Structure-activity relationship of Lycium barbarum polysaccharides / 中国中药杂志

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.

Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea / 中国中药杂志

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.

Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation / 中国中药杂志

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Usefulness of endoscopic ultrasound for acquiring the pathological diagnosis of gastrointestinal lymphoma.

BACKGROUND AND STUDY AIMS: This study aims to assess the value of endoscopic ultrasound (EUS) for acquiring a pathological diagnosis of gastrointestinal lymphoma (GIL). PATIENTS AND METHODS: We retrospectively reviewed all GIL patients who underwent EUS from November 2011 to July 2020 at Fudan University Shanghai Cancer Center. All patients with pathologically confirmed GIL were included. The characteristics of the lesions were recorded, and the efficacy for acquiring pathologic diagnosis between white light endoscopy (WLE) and EUS was analyzed. RESULTS: In total, 404 patients with GIL who underwent EUS examination were included in this study. GIL was confirmed in 143 cases by after EUS judgment biopsy (AEJ biopsy), 11 cases by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), 293 cases by WLE biopsy, and 10 cases by surgical pathology for repeated negative pathologic results from EUS and WLE. Among all cases, 78.71% (318/404) were T1-T2, whereas 32.18% (130/404) were determined to have multiple lesions in the digestive tract wall. The positive rates of the WLE biopsy and AEJ biopsy of the involved gastric wall were 77.93% (293/376) and 89.38% (143/160), respectively. Twelve cases showed diffuse thickening of the gastric wall, and the total positive rate of EUS was 91.67% but 0% for WLE with this type of GIL. The total positive rate and positive rate during the first examination of EUS were all significantly higher than those of WLE. Moreover, 19.68% of the patients showed negative results during their WLE examination and then received a positive pathologic diagnosis upon EUS examination, but none had the opposite process. CONCLUSIONS: EUS was found to be a better tool for acquiring a pathological diagnosis of GIL than conventional WLE, especially for GIL similar to linitis plastica.

Metagenomic analysis of microbial communities and antibiotic resistance genes in spoiled household chemicals.

Numerous attempts have been utilized to unveil the occurrences of antibiotic resistance genes (ARGs) in human-associated and non-human-associated samples. However, spoiled household chemicals, which are usually neglected by the public, may be also a reservoir of ARGs because of the excessive and inappropriate uses of industrial drugs. Based upon the Comprehensive Antibiotic Research Database, a metagenomic sequencing method was utilized to detect and quantify Antibiotic Resistance Ontology (AROs) in six spoiled household chemicals, including hair conditioner, dishwashing detergent, bath shampoo, hand sanitizer, and laundry detergent. Proteobacteria was found to be the dominant phylum in all the samples. Functional annotation of the unigenes obtained against the KEGG pathway, eggNOG and CAZy databases demonstrated a diversity of their functions. Moreover, 186 types of AROs that were members of 72 drug classes were identified. Multidrug resistance genes were the most dominant types, and there were 17 AROs whose resistance mechanisms were categorized into the resistance-nodulation-cell division antibiotic efflux pump among the top 20 AROs. Moreover, Proteobacteria was the dominant carrier of AROs with the primary resistance mechanism of antibiotic efflux. The maximum temperature of the months of collection significantly affected the distributions of AROs. Additionally, the isolated individual bacterium from spoiled household chemicals and artificial mixed communities of isolated bacteria demonstrated diverse resistant abilities to different biocides. This study demonstrated that there are abundant microorganisms and a broad spectrum profile of AROs in spoiled household chemicals that might induce a severe threat to public healthy securities and merit particular attention.

Comparison between the Linked Color and White Light Imaging Combined Score in the Evaluation of High-Risk Population of Gastric Cancer.

BACKGROUND: For patients undergoing gastroscopy, it is necessary to judge whether there is Helicobacter pylori infection, atrophy/intestinal metaplasia. This study aimed to evaluate and compare the light color imaging (LCI) and white light imaging (WLI) combined score during gastroscopy. METHODS: Each included patient underwent normalized gastroscopy with WLI and LCI, and all notable findings were photographed. Four endoscopists reviewed the endoscopic images of each patient. The clinical information, results of the H. pylori tests were unavailable at review. The total LCI and WLI scores of each patient were calculated and their detection in high-risk populations of gastric cancer were evaluated. The diagnostic values of LCI and WLI for intestinal metaplasia were also calculated. RESULTS: In total, 392 patients were included in the study. The degree of inflammation and proportion of active inflammation cases were significantly higher in the H. pylori gastritis group than in the non-H. pylori gastritis group; their endoscopic manifestations were also different. The LCI combined score improved the diagnostic value of each individual observation index in the diagnosis of H. pylori infection compared with the WLI combined score. The sensitivity, specificity, and accuracy were 91.9% (91.9% vs 81.5%), 91.1% (91.1% vs 80.2%), and 95.8% (95.8% vs 93.2%), respectively. The accuracy of LCI in the diagnosis of intestinal metaplasia was higher than that of WLI (83.4% vs 69.6%). CONCLUSION: The LCI and LCI combined score improved the diagnosis of H. pylori gastritis and intestinal metaplasia, and it is considered valuable in identifying the high-risk population of gastric cancer.

Repairing of Subchondral Defect and Articular Cartilage of Knee Joint of Rabbit by Gadolinium Containing Bio-Nanocomposites.

A variety of gadolinium (Gd) based nanoparticles (NPs) were synthesized due to the unique magnetic properties of Gd-containing rare earth compounds and the particularity of micro/nano-materials, which were then incorporated into hydroxyapatite (HA) to obtain inorganic-organic composite materials. Then, HA/Gd NPs containing slow-release transforming growth factor (TGF-ß1) were harvested. Adipose-derived stem cells (ADSCs) were extracted from the adipose tissue of a four-month-old New Zealand white rabbit. HA/Gd NPs were attached to absorbable gelatin sponge to obtain HA/Gd NPs/gelatin sponge composite scaffold. In addition, the third generation ADSCs were taken and cultured in the composite scaffold, so that ADSCs-HA/Gd bio-nanocomposites were obtained. The in vitro culture test of osteoblast MC3T3-E1 showed that Gd-containing NPs had good biocompatibility. The prepared HA/Gd NPs loaded with TGF-ß1 were spherical, with an average particle size of (9.16 ± 3.16) µm. The NPs were easy to aggregate and adherent. Enzyme-linked immunosorbent assay (ELISA) test results showed that TGF-ß1 in NPs was sustained and released continuously for 29 days. HA/Gd NPs/gelatin sponge composite scaffold combined with ADSCs were co-cultured for three days, and the electron microscope showed that the HA/Gd NPs were dispersed, and the cells could adhere and grow well. Then, animal models of rabbit knee articular cartilage defects were established and were rolled into three groups (ADSCs-HA/Gd nano group, HA/Gd nano scaffold group, and blank control). The repair area of the rabbit knee of ADSCs-HA/Gd nano group was smooth and flat, the scaffold was absorbed, the toluidine blue stain was positive, and the type II collagen immunohistochemical stain was positive. In general, ADSCs-HA/Gd nanomaterials were helpful for chondrogenic cell differentiation and had certain adoption prospects in the field of tissue engineering to repair cartilage defects.

Comparisons of Respiratory Pupal Gill Development in Black Flies (Diptera: Simuliidae) Shed Light on the Origin of Dipteran Prothoracic Dorsal Appendages.

During the transformation of immature aquatic dipteran insects to terrestrial adults, the prothoracic pupal respiratory organ enables pupae to cope with flood-drought alternating environments. Despite its obvious importance, the biology of the organ, including its development, is poorly understood. In this study, the developing gills of several Simulium Latreille (Diptera: Simuliidae) spp. were observed using serial histological sections and compared with data on those of other dipteran families published previously. The formation of some enigmatic features that made the Simulium gill unique is detailed. Through comparisons between taxa, we describe a common developmental pattern in which the prothoracic dorsal disc cells not only morph into the protruding respiratory organ, which is partially or entirely covered with a cuticle layer of plastron, but also invaginate to form a multipart internal chamber that in part gives rise to the anterior spiracle of adult flies. The gill disc resembles wing and leg discs and undergoes cell proliferation, axial outgrowth, and cuticle sheath formation. The overall appendage-like characteristics of the dipteran pupal respiratory organ suggest an ancestral form that gave rise to its current forms, which added more dimensions to the ways that arthropods evolved through appendage adaptation. Our observations provide important background from which further studies into the evolution of the respiratory organ across Diptera can be carried out.

The mechanism by which Peganum harmala L. inhibits high glucose-induced tube formation in endothelial cells / 药学学报

The study investigates the mechanism by which Peganum harmala L. (Luotuopeng, LTP) inhibits tube formation in retinal vascular endothelial cells. Tube formation was induced by treatment of retinal vascular endothelial cells with glucose. The cells were divided into a normal group, model group, and an LTP group. The total length of tube formation was measured. The active components, targets, and pathway by which LTP acts in the treatment of diabetic retinopathy was explored by network pharmacology. The mRNA expression levels of targets [extracellular signal-regulated kinase 2 (ERK2), phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), serine/threonine-protein kinase 1 (AKT1)] related to the mitogen-activated protein kinase (MAPK) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway was measured by real-time PCR. The results of tube formation indicated that compared with the normal group, the total tube length increased in the model group (P < 0.01); after the treatment with LTP, the total tube length decreased compared with the model group (P < 0.01). Network pharmacology revealed that the targets of LTP included PIK3CA, AKT1, and ERK2, and the pathways involved the MAPK signaling pathway and the VEGF signaling pathway. Real-time PCR indicated that compared with the normal group, the mRNA expression levels of ERK2, PIK3CA and AKT1 were elevated in the model group (P < 0.05); after treatment with LTP, the mRNA expression levels of ERK2, PIK3CA and AKT1 decreased compared with the model group (P < 0.05). LTP may inhibit retinal vascular endothelial cell tube formation by regulating the MAPK signaling pathway and the VEGF signaling pathway. This study confirms the multi-targets and multi-pathways of LTP and provides a basis for its use in the treatment of diabetic retinopathy．

Design, synthesis and antifungal activity of threoninamide carbamate derivatives via pharmacophore model.

Thirty-six novel threoninamide carbamate derivatives were designed and synthesised using active fragment-based pharmacophore model. Antifungal activities of these compounds were tested against Oomycete fungi Phytophthora capsici in vitro and in vivo. Interestingly, compound I-1, I-2, I-3, I-6 and I-7 exhibited moderate control effect (>50%) against Pseudoperonospora cubensis in greenhouse at 6.25 µg/mL, which is better than that of control. Meanwhile most of these compounds exhibited significant inhibitory against P. capsici. The other nine fungi were also tested. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum, P. piricola and R. solan in vitro with EC50 values of 3.74-9.76 µg/mL. It is possible that the model is reliabile and this method can be used to discover lead compounds for the development of fungicides.

Differentiation of solid-pseudopapillary tumors of the pancreas from pancreatic neuroendocrine tumors by using endoscopic ultrasound.

BACKGROUND AND AIM: To differentiate solid-pseudopapillary tumors (SPTs) of the pancreas from pancreatic neuroendocrine tumors (pNETs) by endoscopic ultrasound. METHODS: We retrospectively reviewed all patients with SPTs and pNETs who underwent endoscopic ultrasound (EUS) from May 2012 to August 2018 at the Fudan University Shanghai Cancer Center. We included patients confirmed pathologically with a surgical biopsy or with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The demographic data of the patients, characteristics of the lesions and overall survival data of patients with these two diseases were further compared. RESULTS: A total of 147 pNET patients and 21 SPT patients were included in our study. The mean ages of the patients in the SPT and pNET groups were 35.95years and 54.30years, respectively. There were more females in the SPT group than in the pNET group (71.43% vs. 40.82%). The patients in the pNET group had significantly more lymphatic metastases and visceral organ metastases than the patients in the SPT group. A larger proportion of pNET lesions than SPT lesions had homogeneous echo patterns and were hypervascular. Cystic components and calcification components were more often observed in the SPT lesions than in the pNET lesions. In the multivariate logistic regression analysis, the hypervascularization (OR: 6.528, 95% CI: 1.562-27.285, P=0.010) and cystic component (OR: 0.106, 95% CI: 0.019-0.597, P=0.011) variables resulted in the best discrimination of patients with SPTs from patients with pNETs. Survival among patients with SPTs was higher than that among patients with pNETs at all points in the follow-up period. CONCLUSIONS: SPTs tended to occur in younger people and were more common in women. Pancreatic neuroendocrine tumors tended to form metastases more often than SPTs. The blood supply and cystic components of the lesions may have novel potential diagnostic utility for differentiating SPTs from pNETs.