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.

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.

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.

Antifungal Activity and Physicochemical Properties of a Novel Antimicrobial Protein AMP-17 from Musca domestica.

Antimicrobial peptides (AMPs) are cationic small peptide chains that have good antimicrobial activity against a variety of bacteria, fungi, and viruses. AMP-17 is a recombinant insect AMP obtained by a prokaryotic expression system. However, the full antifungal activity, physicochemical characteristics, and cytotoxicity of AMP-17 were previously unknown. AMP-17 was shown to have good antifungal activity against five pathogenic fungi, with minimum inhibitory concentrations (MIC) of 9.375-18.75 µg/ml, and minimum fungicidal concentrations (MFC) of 18.75-37.5 µg/ml. Notably, the antifungal activity of AMP-17 against Cryptococcus neoformans was superior to that of other Candida spp. In addition, the hemolytic rate of AMP-17 was only 1.47%, even at the high concentration of 16× MIC. AMP-17 was insensitive to temperature and high salt ion concentration, with temperatures of 98°C and -80°C, and NaCl and MgCl2 concentrations of 50-200 mmol/l, having no significant effect on antifungal activity. However, AMP-17 was sensitive to proteases, trypsin, pepsin, and proteinase K. The elucidation of antifungal activity, physicochemical properties and cytotoxicity of AMP-17 provided an experimental basis for its safety evaluation and application, as well as indicated that AMP-17 might be a promising drug.Antimicrobial peptides (AMPs) are cationic small peptide chains that have good antimicrobial activity against a variety of bacteria, fungi, and viruses. AMP-17 is a recombinant insect AMP obtained by a prokaryotic expression system. However, the full antifungal activity, physicochemical characteristics, and cytotoxicity of AMP-17 were previously unknown. AMP-17 was shown to have good antifungal activity against five pathogenic fungi, with minimum inhibitory concentrations (MIC) of 9.375­18.75 µg/ml, and minimum fungicidal concentrations (MFC) of 18.75­37.5 µg/ml. Notably, the antifungal activity of AMP-17 against Cryptococcus neoformans was superior to that of other Candida spp. In addition, the hemolytic rate of AMP-17 was only 1.47%, even at the high concentration of 16× MIC. AMP-17 was insensitive to temperature and high salt ion concentration, with temperatures of 98°C and ­80°C, and NaCl and MgCl2 concentrations of 50­200 mmol/l, having no significant effect on antifungal activity. However, AMP-17 was sensitive to proteases, trypsin, pepsin, and proteinase K. The elucidation of antifungal activity, physicochemical properties and cytotoxicity of AMP-17 provided an experimental basis for its safety evaluation and application, as well as indicated that AMP-17 might be a promising drug.

C-Reactive Protein to Albumin Ratio in Colorectal Cancer: A Meta-Analysis of Prognostic Value.

BACKGROUND: The relationship between pretreatment C-reactive protein to albumin ratio (CAR) and colorectal cancer (CRC) prognosis has been extensively studied in various tumors. However, little is known on CAR and its association with prognosis in CRC. This study aims to investigate the prognostic value of pretreatment CAR in CRC. METHODS: We conducted a systematic search of MEDLINE, EMBASE, and Cochrane Library databases for eligible studies evaluating the associations of CAR with survival and/or clinicopathology of CRC. Overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and clinicopathological features were synthesized and compared. RESULTS: Nine studies including 3431 patients were analyzed in this meta-analysis. Pooled results showed that elevated pretreatment CAR was associated with poor OS (pooled hazards ratio [HR]: 2.18, 95% confidence interval [CI]: 1.70-2.78, P < .001) and DFS/RFS (pooled HR: 2.36, 95% CI: 1.40-3.98, P < .001). Moreover, elevated pretreatment CARs were correlated with male patients, large tumor diameter, late III-IV tumor node metastasis stage tumors, high serum carcinoembryonic antigen and carbohydrate antigen 19-9, and presence of lymphatic invasion and venous invasion. CONCLUSION: Elevated pretreatment CAR could be an adverse prognostic indicator in patients with CRC.

Validation and head-to-head comparison of four models for predicting malignancy of intraductal papillary mucinous neoplasm of the pancreas: A study based on endoscopic ultrasound findings.

BACKGROUND: Several models are currently available for predicting the malignancy of pancreatic intraductal papillary mucinous neoplasm (IPMN), namely, the Pancreatic Surgery Consortium (PSC), the Japan Pancreas Society (JPS), the Johns Hopkins Hospital (JHH), and the Japan-Korea (JPN-KOR) models. However, a head-to-head comparison that shows which model is more accurate for this individualized prediction is lacking. AIM: To perform a head-to-head comparison of the four models for predicting the malignancy of pancreatic IPMN. METHODS: A total of 181 patients with IPMN who had undergone surgical resection were identified from a prospectively maintained database. The characteristics of IPMN in patients were recorded from endoscopic ultrasound imaging data and report archives. The performance of all four models was examined using Harrell's concordance index (C-index), calibration plots, decision curve analyses, and diagnostic tests. RESULTS: Of the 181 included patients, 94 were categorized as having benign disease, and the remaining 87 were categorized as having malignant disease. The C-indexes were 0.842 [95% confidence interval (CI): 0.782-0.901], 0.704 (95%CI: 0.626-0.782), 0.754 (95%CI: 0.684-0.824), and 0.650 (95%CI: 0.483-0.817) for the PSC, JPS, JHH, and JPN-KOR models, respectively. Calibration plots showed that the PSC model had the least pronounced departure from ideal predictions. Of the remaining three models, the JPS and JHH models underestimated the probability of malignancy, while the JPN-KOR model overestimated the malignant potential of branch duct-IPMN. Decision curve analysis revealed that the PSC model resulted in a better clinical net benefit than the three other models. Diagnostic tests also showed a higher accuracy (0.801) for the PSC model. CONCLUSION: The PSC model exhibited the best performance characteristics. Therefore, the PSC model should be considered the best tool for the individualized prediction of malignancy in patients with pancreatic IPMN.

Pinoresinol promotes MC3T3­E1 cell proliferation and differentiation via the cyclic AMP/protein kinase A signaling pathway.

Estradiol (E2) is a first­line drug for osteoporosis (OP) treatment via promotion of osteoblastic proliferation and differentiation. However, a long­term use of E2 would produce side effects thus, it is imperative to discover safer and more effective drugs. Pinoresinol (PINO) has a similar chemical structure to E2. The present study aimed to investigate whether PINO could promote osteoblastic proliferation and differentiation and the potential mechanisms. After treatment with 0.1 µg/l PINO for 2 days, MC3T3­E1 cell migration was assessed by wound healing assay. Estrogen (E2) treatment served as a positive control. RT­qPCR and western blotting were used for mRNA and protein expression analyses. Alkaline phosphatase (ALP) activity assay and Alizarin red staining were performed to investigate the calcification and mineralization, and the cyclic AMP (cAMP) level was detected by enzyme­linked immunosorbent assay (ELISA). H89, an inhibitor of protein kinase A (PKA), was introduced to verify the role of cAMP/PKA in the effect of PINO on MC3T3­E1 cells. Cell viability was the highest under 48 h of 0.1 µg/l PINO treatment. After treatment with PINO, a significant increase was observed in the migration rate and the expression of collagen type I (Col­I), ALP, osteopontin (OPN), runt­related transcription factor 2 (Runx2) and bone morphogenetic protein­2 (BMP­2) (P<0.01). The ALP activity and Alizarin red size in PINO and E2 groups were notably increased. The increased cAMP, PKA and phosphorylated cAMP response element­binding protein (CREB) levels were also observed in the PINO group. Furthermore, H89 co­treatment abolished the positive effects of PINO on cell viability and migration. PINO had similar effects to E2 on the osteoblastic proliferation and differentiation, and these positive effects may be attributed to the regulation of the cAMP/PKA signaling pathway.