CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a poor prognosis and growing incidence. In this study, we explored the potential roles of CDK1, CDK2, CDK4, and CDK6 in the progression of early-stage PDAC. Clinicopathologic and mRNA expression data and treatment information of 140 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy were obtained from the Cancer Genome Atlas data set. Our bioinformatic analysis showed that higher CDK1, CDK2, CDK4, or CDK6 expression was associated with a shorter median survival of the early-stage PDAC patients. Of note, in the low-proliferating pancreatic cancer group, CDKs expressions were significantly associated with proteins functioning in apoptosis, metastasis, immunity, or stemness. Among the low-proliferating PDAC, higher expression of CDK1 was associated with the shorter survival of patients, suggesting that CDK1 may regulate PDAC progression through cell cycle-independent mechanisms. Our experimental data showed that CDK1 knockdown/inhibition significantly suppressed the expression levels of AHR and POU5F1, two critical proteins functioning in cancer cell metastasis and stemness, in low-proliferating, but not in high-proliferating pancreatic cancer cells. In all, our study suggests that CDKs regulate PDAC progression not only through cell proliferation but also through apoptosis, metastasis, immunity, and stemness.

Evaluation of inducing activity of CIP elicitors from diverse sources based on monosaccharide composition and physiological indicators.

Application of elicitors can greatly enhance plant immune resistance against pathogens. However, it is still obscure whether elicitor activity is influenced by diverse sources. This study investigated the effect of foliar spraying of 19 batches of Chrysanthemum indicum polysaccharides (CIPs) on the disease resistance of Atractylodes macrocephala Koidz. (A. macrocephala) and explored the main reasons for the differences of inducing activity of CIP elicitors. PCA, OPLS-DA, grey relational analysis and entropy weight method had good predictability for the activity evaluation of CIP elicitors and other plant-derived elicitors. The results showed that 19 batches of CIPs had definite regional differences in inducing activity and monosaccharide content. CIP elicitors with high inducing activity could significantly increase the accumulation of Atractylenolide Ⅱ and Atractylenolide Ⅲ, the mRNA relative transcription level of CAT, POD, PAL genes, the amount of pH change in the medium and effectively reduce the disease index of A. macrocephala. Furthermore, CIP with high inducing activity exhibited the high contents of Rha, Ara and GalA, which might be the main contributor to their high activity. The evaluation procedure developed in this work can be applied for screening CIP elicitors with high inducing activity, and it lays a foundation for identifying more functional elicitors related to plant immune resistance.

A. macrocephala polysaccharide induces alterations to gut microbiome and serum metabolome in constipated mice.

Atractylodes macrocephala polysaccharide (AC1) is extracted from the root of the Chinese herb Atractylodes Macrocephala and is used in the treatment of constipation due to its effects on strengthening cellular immunity and regulating intestinal function. In this study, Metagenomics and Metabolomic are used to analyze the effects of AC1 on the gut microbiota and host metabolites in mice models of constipation. The results show that the abundance of Lachnospiraceae_bacterium_A4, Bact-oides_vulgatus and Prevotella_sp_CAG:891 increased significantly, indicating that AC1-targeted strain modulation effectively alleviated the dysbiosis of the gut microbiota. Besides, the microbial alterations also influenced the metabolic pathways of the mice, including tryptophan metabolism, unsaturated fatty acid synthesis and bile acid metabolism. The physiological parameters of the mice treated with AC1 are improved, such as tryptophan in the colon, 5-hydroxytryptamine (5-HT) and short-chain fatty acids (SCFAs). In conclusion, AC1 as a probiotic can regulate intestinal flora to normal levels and achieve the effect of treating constipation.

Diagnostic serum biomarkers associated with ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune rheumatic disease that mostly affects the axial skeleton. This study aimed to investigate reliable diagnostic serum biomarkers for AS. Serum samples were collected from 20 AS patients and 20 healthy controls (HCs) and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The differential metabolites between the AS patients and HCs were profiled using univariate and multivariate statistical analyses. Pathway analysis and a heat map were also conducted. Random forest (RF) analysis and the least absolute shrinkage and selection operator (LASSO) were used to establish predictive and diagnostic models. After controlling the variable importance in the projection (VIP) value > 1 and false discovery rate (FDR) < 0.05, a total of 61 differential metabolites were identified from 995 metabolites, which exhibited significant differences in the pathway analysis and heat map between the AS patients and HCs. RF as a predictive model also identified differential metabolites with 95% predictive accuracy and a high area under the curve (AUC) of 1. A diagnostic model comprising nine metabolites (cysteinylglycine disulfide, choline, N6, N6, N6-trimethyllysine, histidine, sphingosine, fibrinopeptide A, glycerol 3-phosphate, 1-linoleoyl-GPA (18:2), and fibrinopeptide A (3-16)) was generated using LASSO regression, capable of distinguishing HCs from AS with a high AUC of 1. Our results indicated that the UPLC-MS/MS analysis method is a powerful tool for identifying AS metabolite profiles. We developed a nine-metabolites-based model serving as a diagnostic tool to separate AS patients from HCs, and the identified diagnostic biomarkers appeared to have a diagnostic value for AS.

Cytokines and chemokines involved in HLA-B27-positive ankylosing spondylitis-associated acute anterior uveitis.

Purpose: Acute anterior uveitis (AAU) is the most common extra-articular symptom of ankylosing spondylitis (AS). This study aims to reveal the cytokines and chemokines involved in the immunopathogenesis of human leucocyte antigen (HLA)-B27+ AS-associated AAU. Methods: Twenty-one HLA-B27+ AS-associated AAU patients and 21 healthy controls (HCs) were recruited for this study. Serum cytokine concentrations in all 42 subjects were determined by the Meso Scale Discovery (MSD) electrochemiluminescence method. In each sample, 34 cytokines, 10 chemokines, eight angiogenesis mediators, and four vascular injury mediators were measured. The differences in cytokine and chemokine concentrations were compared between the two groups. Results: Concentrations of serum IL-3, TNF-α, IL-6, IL-17D, IL-22, IP10/CXCL10, MIP-3α/CCL20, sFlt-1/VEGFR-1, CRP, and MCP-4/CCL13 were significantly higher in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). In contrast, concentrations of serum IL-4, IL-8, MIP-1α/CCL3, Eotaxin-3/CCL26, PlGF, VEGF-C, and VEGF-D were significantly lower in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). Conclusions: Significant differences were detected in the levels of several cytokines and chemokines in the serum of HLA-B27+ AS-associated AAU compared with HCs. Some novel differential cytokines and chemokines that have not been reported in other kinds of uveitis were also identified. These results reveal the underlying pathogenesis of HLA-B27+ AS-associated AAU and could potentially aid in clinical diagnosis.

Test and Detection of Antifreezing and Anticorrosion Performance of Carbon Nanofiber Bridge Concrete.

In order to solve the problems of carbon nanotubes, steel fibers, and carbon nanotubes + steel fibers on the compressive strength and impact resistance of concrete, the author proposes a test method for the frost resistance and corrosion resistance of carbon nanofiber bridge concrete. Using carbon nanotubes and steel fibers as reinforcing materials, the effects of carbon nanotubes and steel fibers on the compressive strength and impact resistance of concrete were studied. Experimental results show that incorporating carbon nanotubes and steel fibers can improve the compressive strength of concrete. Compared with the single-doped carbon nanotubes, the single-doped steel fiber has a greater effect on the improvement of the impact resistance of the concrete. The toughness and ductility of carbon nanotubes and steel fiber reinforced concrete are improved again compared with that of single steel fiber reinforced concrete. The effect of adding 1% steel fiber +0.30% carbon nanotubes is the most significant in enhancing the performance of concrete. Conclusion. The synergistic effect of carbon nanotubes and steel fibers is more conducive in complementing each other's advantages and improving the performance of concrete.

Structural characterization and evaluation the elicitors activity of polysaccharides from Chrysanthemum indicum.

This research evaluates the elicitors activity and structure characterization of four Chrysanthemum indicum polysaccharides (CIPs) which were isolated from C. indicum, obtained CIP1, CIP2, CIP3, CIP4. Results demonstrated that there was a distinct difference in inducibility and CIP3 was significantly stronger than other CIPs through bioactivity-tests. Taking CIP3 with total carbohydrate content 91.93 % as a representative, its structure was elucidated as a relative molecular weight of 8. 741 × 103 g/mol and mainly composed of xylose, galacturonic acid, galactose and glucuronic acid. Through GC, IR and NMR, CIP3 was determined to possess a backbone comprised of T-α-d-GalpA, 1,4-α-d-GlcpA, 1,2-α-d-Xylp, 1,3-α-l-Rhap, 1,2,4-α-l-Rhap and sidechains comprised of 1,3-ß-d-Galp, 1,6-α-d-Galp, T-α-Glcp, 1,3-ß-d-Glcp, 1,4-α-d-Glcp, 1,3,4-α-d-Manp, T-α-l-Fucp. Further results indicated that CIP3 with active sidechains could significantly increase the expression of defense genes in Atractylodes macrocephala Koidz (AM). It is believed that the sidechains of CIP3 were necessary to its elicitor activity via bioactivity tests.

Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice.

The asparaginase and isoaspartyl peptidase 1 (ASRGL1) is an L-asparaginase and beta-aspartyl peptidase enzyme that may be involved in the formation of L-aspartate, a neurotransmitter that can operate as an excitatory neurotransmitter in some brain regions. Although variants in ASRGL1 have been reported in retinitis pigmentosa (RP) patients, the in vivo functions and mechanisms of ASRGL in RP remains unknown due to the lack of suitable disease models. To explore the role of ASRGL in RP, we generated an Asrgl1 knockout mouse model (Asrgl1 KO) using the CRISPR/Cas9 technique. Asrgl1 ablation in mice led to an attenuated electroretinogram (ERG) response around 8 months. The thickness of the outer nuclei layer (ONL) started to decrease around 9 months in Asrgl1 KO mice and gradually intensified at 12 and 15 months. Immunostaining revealed thinner inner segment (IS) and thinner outer segment (OS) as well as the progressive degeneration of rod and cone cells in Asrgl1 KO mice. One hundred forty-nine transcriptional differentially expressed genes (DEGs) were found by RNA-seq in Asrgl1 KO retina. These DEGs were linked to a number of biological processes that were considerably enriched, including gastrointestinal disease and organismal injury and abnormalities. By analysis of canonical pathways, glucocorticoid receptor signaling was the most significant canonical pathway altered in Asrgl1 KO retina. Several molecules, including NFE2L2, IL-4, Foxp3, and Fos, were in the central nodes of the interaction network in Asrgl1 KO retina. In summary, our study provided a knockout mouse model for a better understanding of the molecular mechanism for ASRGL1-related RP.

Multicenter surveillance study of surgical site infection and its risk factors in radical resection of colon or rectal carcinoma.

BACKGROUND: Colorectal surgery is associated with high rates of surgical site infection (SSI). We investigated SSI in radical resection of colon or rectal carcinoma and its epidemiological distribution in 26 hospitals in China. METHODS: We conducted prospective surveillance of patients who underwent radical resection of colon or rectal carcinoma in 26 selected hospitals from January 2015 to June 2016.An information system monitored all of the surgical inpatients. Infection control professionals observed the inpatients with suspected SSI who had been screened by the system at the bedside. The infection status of the incisions was followed up by telephone 1 month after the operation. RESULTS: In total, 5729 patients were enrolled for the two operations; SSIs occurred in 206 patients, and the infection rate was 3.60%. The incidence of SSI after radical resection of rectal carcinoma (5.12%; 119/2323) was 2.1 times higher than that after radical resection of colon carcinoma (2.55%; 87/3406) (P < 0.0001). Additionally, in the colon versus rectal groups, the rate of superficial incisional SSI was 0.94% versus 2.28% (P < 0.0001), the rate of deep incisional SSI was 0.56% versus 1.11% (P = 0.018), and the rate of organ space SSI was 1.06% versus 1.72% (P = 0.031), respectively. The most common pathogens causing SSIs after radical resection of colon carcinoma were Escherichia coli (21/38) and Pseudomonas aeruginosa (5/38). Escherichia coli (24/65) and Enterococcus spp. (14/65) were the two most common pathogens in the rectal group. The multivariate logistic regression analysis showed that only the operating time and number of hospital beds were common independent risk factors for SSIs after the two types of surgery. CONCLUSION: This multicenter study showed that there were significant differences in the incidence of SSIs, three types of SSIs, and some risk factors between radical resection of colon carcinoma and rectal carcinoma.

[Effect of anisodamine on myocardial connexin 43 expression in pig after resuscitation from cardiac arrest].

OBJECTIVE: To investigate the effect of anisodamine on the expression of connexin 43 (Cx43) in swine ventricular myocardium after resuscitation from cardiac arrest. METHODS: The experiment was conducted on healthy pigs, and they were randomly divided into three groups, namely sham group, epinephrine group (control group) and anisodamine group (experimental group, animals were resuscitated combined with injection of 0.4 mg/kg of anisodamine), with 5 pigs in each group. Model of ventricular fibrillation was reproduced by alternating current challenge, and cardiopulmonary resuscitation (CPR) was performed 8 minutes after cardiac arrest. Left ventricular myocardium was harvested at 24 hours after restoration of spontaneous circulation. The expression and distribution of Cx43 were observed by immunofluorescence, Cx43 mRNA expression was assessed with reverse transcription-polymerase chain reaction (RT-PCR), and the protein expressions of Cx43 and phosphorylation of Cx43 (p-Cx43) were analyzed by Western Blot. RESULTS: The positive expression of Cx43 in ventricular muscle was distributed uniformly, mostly at the end-to-end linkage of myocardial cells, with a few side-to-side linkage in sham group. The positive expression of Cx43 in control group was significantly weaker than that in the sham group, and the signal intensity was significantly declined (4.35±2.10 vs. 10.02±3.66, P < 0.01). The positive expression of Cx43 at the end-to-end linkage and side-to-side linkage was irregular in experimental group, and the signal intensity was obviously higher than that in the control group (7.91±2.54 vs. 4.35±2.10, P < 0.05), but it was significantly weaker than that in the sham group (7.91±2.54 vs. 10.02±3.66, P < 0.05). For control group and experimental group, the Cx43 mRNA and protein expressions were significantly lower than those of the sham group [Cx43 mRNA (A value): 0.32±0.05, 0.32±0.03 vs. 0.48±0.07; Cx43 protein (A value): 0.43±0.03, 0.50±0.07 vs. 0.65±0.04, all P < 0.01], and there were no significant differences between experimental group and control group (all P > 0.05). The p-Cx43 protein expression of control group was significantly lower than that of the sham group (A value: 0.22±0.03 vs. 0.37±0.06, P < 0.01), and it was significantly higher in the experiment group than that in the control group (A value: 0.29±0.07 vs. 0.22±0.03, P < 0.01), but there was no significant difference with the sham group (P > 0.05). No significant difference in p-Cx43/Cx43 was found among sham, control, and experiment groups (0.57±0.09, 0.51±0.05, 0.58±0.06, all P > 0.05). CONCLUSIONS: Anisodamine can improve the abnormal expression of Cx43 in ventricular muscle of pigs with cardiac arrest, which may be related to the protection effect of anisodamine on cardiac conduction.

[Medical rescue of China National Earthquake Disaster Emergency Search and Rescue Team in Lushan earthquake].

OBJECTIVE: To summarize and analyze the medical mission of China National Earthquake Disaster Emergency Search and Rescue Team (CNESAR) in Lushan earthquake, to promote the medical rescue effectiveness incorporated with search and rescue. METHODS: Retrospective analysis of medical work data by CNESAR from April 21th, 2013 to April 27th during Lushan earthquake rescue, including the medical staff dispatch and the wounded case been treated. RESULTS: The reasonable medical corps was composed by 22 members, including 2 administrators, 11 doctors [covering emergency medicine, orthopedics (joints and limbs, spinal), obstetrics and gynecology, gastroenterology, cardiology, ophthalmology, anesthesiology, medical rescue, health epidemic prevention, clinical laboratory of 11 specialties], 1 ultrasound technician, 5 nurses, 1 pharmacist, 1 medical instrument engineer and 1 office worker for propaganda. There were two members having psychological consultants qualifications. The medical work were carried out in seven aspects, including medical care assurance for the CNESAR members, first aid cooperation with search and rescue on site, clinical work in refugees' camp, medical round service for scattered village people, evacuation for the wounded, mental intervention, and the sanitary and anti-epidemic work. The medical work covered 24 small towns, and medical staff established 3 medical clinics at Taiping Town, Shuangshi Town of Lushan County and Baoxing County. Medical rescue, mental intervention for the old and kids, and sanitary and anti-epidemic were performed at the above sites. The medical corps had successful evacuated 2 severe wounded patients and treated the wounded over thousands. Most of the wounded were soft tissue injuries, external injury, respiratory tract infections, diarrhea, and heat stroke. CONCLUSIONS: Compared with the rescue action in 2008 Wenchuan earthquake, the aggregation and departure of rescue team in Lushan earthquake, the traffic control order in disaster area, the self-aid and buddy aid are better, which give rise to the casualties to the lowest. The medical mission incorporated with search and rescue work showed that the medical performance manner altered with stages, the medical staff match changed with the mission, and the focus related with rescue time.

[Discussion about health assessment and epidemic prevention mode for China National Earthquake Disaster Emergency Search and Rescue Team in Lushan earthquake].

OBJECTIVE: To discuss health assessment and epidemic prevention in earthquake rescue, to establish emergency health and epidemic prevention mode for the national earthquake emergency medical rescue team scientifically, and to provide references and consultations for emergency hygiene and epidemic prevention measures in disaster medicine. METHODS AND RESULTS: China National Earthquake Disaster Emergency Search and Rescue Team gathered and evaluated environment, food, drinking water and other health related information around more than 2000 earthquake victims in Baoxing County, Shuangshi Town and Qingren Township from 20th April 2013 to 27th by using methods such as field epidemiological investigations. The national earthquake emergency medical rescue team spread comprehensive evaluation focusing on the local epidemics, find out the starting point of epidemic prevention, and then built reporting system in disaster area. The team also formulated the emergency detection system of food and drinking water and carried out health education. CONCLUSION: After the golden 72 hours, by comprehensive evaluation the establishment of early response in disaster area and spreading epidemic prevention, this team achieved the full coverage of three in the earthquake area, the resettlement of residents and families in that area and gradually formed a disaster medical rescue hygiene and epidemic prevention mode.

Role of hepatic arterial ischaemia in biliary fibrosis following liver transplantation.

BACKGROUND: In clinical liver transplantation, whether the delay of hepatic arterial ischaemia increases biliary fibrosis or not is controversial. We designed a liver transplantation model to test this controversy and explore its mechanism. METHODS: Twelve dogs were divided into two groups randomly: hepatic arterial ischaemia (HAI) and control groups. In HAI group, hepatic artery was perfused 60 minutes after portal perfusion, but in control group, hepatic arterial perfusion was simultaneous with portal perfusion. The pathological changes of intrahepatic bile ducts were observed. Transforming growth factor beta 1 (TGF-beta1), expressed in epithelial cells of intrahepatic bile duct, was detected by immunohistochemical streptoadividin-biotin complex method. Expressions of Smad3, P-Smad3 and the transcriptional levels of alpha smooth muscle actin (alpha-SMA) mRNA in intrahepatic bile ducts were detected by Western blotting and RT-PCR respectively. RESULTS: Compared with the control group, more collagen deposition and leucocytic infiltration could be seen in biliary vessel walls. Significantly more buffy particles, which are the proteins of TGF-beta1, could be seen in biliary epithelial cells. P-Smad3 and alpha-SMA mRNA (as ratio to corresponding beta-actin) in intrahepatic bile ducts were 1.82 +/- 0.18 and 1.86 +/- 0.73 respectively in HAI group, significantly higher than those in control group (0.59 +/- 0.09 and 0.46 +/- 0.18, respectively). CONCLUSIONS: Hepatic arterial ischaemia could increase the deposition of collagen fibres, trigger the transdifferentiation of myofibroblasts in intrahepatic bile duct and might result in biliary fibrosis by activating the TGF-beta1 signalling pathway.