Search

The 3D printing of porous titanium scaffolds reduces the elastic modulus of titanium alloys and promotes osteogenic integration. However, due to the biological inertness of titanium alloy materials, the implant-bone tissue interface is weakly bonded. A calcium silicate (CS) coating doped with polymetallic ions can impart various biological properties to titanium alloy materials. In this study, CuO and SrO binary-doped CS coatings were prepared on the surface of 3D-printed porous titanium alloy scaffolds using atmospheric plasma spraying and characterized by SEM, EDS, and XRD. Both CuO and SrO were successfully incorporated into the CS coating. The in vivo osseointegration evaluation of the composite coating-modified 3D-printed porous titanium alloy scaffolds was conducted using a rabbit bone defect model, showing that the in vivo osseointegration of 2% CuO-10% SrO-CS-modified 3D-printed porous titanium alloy was improved. The in vitro antimicrobial properties of the 2% CuO-10% SrO-CS-modified 3D-printed porous titanium alloy were evaluated through bacterial platform coating, co-culture liquid absorbance detection, and crystal violet staining experiments, demonstrating that the composite coating exhibited good antimicrobial properties. In conclusion, the composite scaffold possesses both osteointegration-promoting and antimicrobial properties, indicating a broad potential for clinical applications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes ( FGA , FGB , and FGG )., Objectives: To investigate the clinical phenotype, laboratory features, diagnosis, treatment, and prognosis of CFDs., Methods: Clinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed., Results: Among the 93 patients, there were 46 males (49.5%) and 47 females (50.5%), with a median age of 23 years. Fifty-three of 93 (57%) subjects experienced bleeding, 3/93 (3.2%) experienced thrombosis, and 37/93 (39.8%) were asymptomatic. Females were more prone to experience bleeding ( P  < .0001). The 93 patients exhibited prolonged thrombin time, significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen. The 93 patients included 3 with hypofibrinogenemia, 16 with hypodysfibrinogenemia, and 74 with dysfibrinogenemia. Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), and 75.5% (40/53) patients with hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including 1 novel splice mutation. Twenty-eight (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisting of 8 fresh frozen plasma transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions., Conclusion: Most patients with CFDs have mild or no bleeding symptoms. Fg:C combined with fibrinogen antigen and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. The severity of bleeding symptoms was negatively correlated with Fg:C., (© 2024 The Author(s).)

Objective: To characterize the serum bile acid profiles of healthy children in Zhejiang Province. Methods: A cross-sectional study was conducted on 245 healthy children who underwent imaging and laboratory biochemical tests during routine physical examinations at the Children's Hospital of Zhejiang University School of Medicine from January 2020 to July 2022. Overnight fasting venous blood samples were collected, and the concentrations of 18 individual bile acids in the serum were accurately quantitated using tandem mass spectrometry. The concentration difference of bile acid were compared between different genders and to explore the correlation between age and bile acid levels. Used the Mann-Whitney U test for intergroup comparison and Spearman test to correlation analysis. Results: A total of 245 health children with a age of 10 (8, 12) years including 125 boys and 120 girls. There were no significant differences in levels of total bile acids, primary and secondary bile acids, free and conjugated bile acids between the two gender groups (all P >0.05). The serum concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid in girls were significantly higher than those in boys (199.0 (66.9, 276.5) vs. 154.7 (49.3, 205.0) nmol/L, 274.0 (64.8, 308.0) vs. 181.0 (43.8, 209.3) nmol/L, Z =2.06, 2.71, both P <0.05). The serum taurolithocholic acid in both boys and girls were positively correlated with age ( r =0.31, 0.32, both P <0.05). The serum chenodeoxycholic acid and glycochenodeoxycholic acid in the boys group were positively correlated with age ( r =0.20, 0.23, both P <0.05), whereas the serum tauroursodeoxycholic acid in the girls group was negatively correlated with age ( r =-0.27, P <0.05), and the serum cholic acid was positively correlated with age ( r =0.34, P <0.05). Conclusions: The total bile acid levels are relatively stable in healthy children in Zhejiang province. However, individual bile acids showed gender differences and were correlated with age.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease involving the digestive tract, characterized by abdominal pain, diarrhea, rectal bleeding, and so on, which can make patients physically weakened and live difficultly. Although IBD has been recognized for many years, the pathogenesis of IBD has not yet been established and damage to intestinal barrier is thought to be closely associated with IBD. Intestinal barrier is an innate barrier that maintains the homeostasis of the intestinal environment and impedes pathogenic bacteria and toxins, and the endoplasmic reticulum (ER) has recently been found to be involved in maintaining the integrity of intestinal barrier. Endoplasmic reticulum stress (ERS) is a status of endoplasmic reticulum damaged when unfolded or misfolded proteins accumulate in excess of the degradation systematic clearance limit of the misfolded proteins. The regulation of ERS on protein folding synthesis and maintenance of cellular homeostasis is an important factor in influencing the integrity of the intestinal barrier. This paper mainly discusses the relationship between ERS and the intestinal barrier, aiming to understand the regulatory role of ERS on the intestinal barrier and the mechanism and to improve new solutions and notions for the treatment or prevention of IBD., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical effects of the posterior unilateral approach with 270° spinal canal decompression and three-column reconstruction using double titanium mesh cage (TMC) for thoracic and lumbar burst fractures., Materials and Methods: From May 2013 to May 2018, 27 patients with single-level thoracic and lumbar burst fractures were enrolled. Every patient was followed for at least 18 months. Demographic data, neurologic status, back pain, canal compromise, anterior body compression, operative time, estimated blood loss and surgical-related complications were evaluated. Radiographs were reviewed to assess deformity correction, anterior body height correction, bony fusion and TMC subsidence., Results: The average preoperative percentages of canal compromise and anterior body height compression were 58.4% and 50.5%, respectively. All surgeries were successfully completed in one phase, the operative time was 151.5 ± 25.5 min (range: 115-220 min), the estimated blood loss was 590.7 ± 169.9 ml (range: 400-1,000 ml). Neurological function recovery was significantly improved except for 3 grade A patients. The preoperative visual analog scale (VAS) scores for back pain were significantly decreased compared with the values at the last follow-up ( P  = 0.000). The correct deformity angle was 12.4 ± 4.7° (range: 3.9-23.3°), and the anterior body height recovery was 96.7%. The TMC subsidence at the last follow-up was 1.3 ± 0.7 mm (range: 0.3-3.1 mm). Bony fusion was achieved in all patients., Conclusion: The posterior unilateral approach with 270° spinal canal decompression and three-column reconstruction using double TMC is a clinically feasible, safe and alternative treatment for thoracic and lumbar burst fractures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Shi, Ge, Cheng, Lin, Yu, Cheng, Chen, Shen, Chen, Yan, Wang, Chu and Ke.)

Objective: This study aimed to establish a process for the diagnosis and treatment of chronic cough in children suitable at primary hospitals and improve the treatment efficacy rate and improve health economic indicators., Methods: Children who visited the Department of Pediatrics, Affiliated Zhou Pu Hospital of the Shanghai Health Medical College from January to December 2021 were randomly assigned to the intervention group ( n  = 206), in which the diagnosis and treatment process proposed here was applied, and a control group ( n  = 211) that did not follow the intervention pathway and followed a pathway with the doctors usual practice based on his/her previous experience. Patients were followed up and data were collected at weeks 0 (time of enrollment), 2, 4, 8, and 12 to evaluate the efficacy rate and clinical value., Results: (1) No significant differences were detected between the two groups in baseline characteristics, including gender, age, duration of cough (weeks), history of allergy in children and parents, and smoking of family members living in the same household ( p  > 0.05); (2) During the follow-up, all cough symptom scores of the intervention group were lower than the control group. Additionally, at week 12, the treatment efficacy rate of the intervention group (91.70%) was significantly higher than the control group (69.20%) ( p  < 0.05); (3) The quality of life of children in both groups at week 12 was improved compared to the first visit. However, the total score of the intervention group was significantly higher than the control group ( p  < 0.05); (4) At week 12, the referral rate was significantly lower in the intervention group (11.17%) than in the control group (21.33%); (5) The intervention group was better than the control group for the mean monthly medication costs, number of days on errors in childhood, and number of days mistakenly worked by family members at week 12 ( p  < 0.05)., Conclusion: The current process of diagnosis and treatment of chronic cough in children at primary hospitals can improve the effective diagnosis and treatment rate, the quality of life, and other parameters, with good effectiveness and feasibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Shen, Zhang, Zhang and Sheng.)

To assess the amino acid and fatty acid metabolite patterns between infants with and without bronchopulmonary dysplasia in different nutritional stages after birth and identify metabolic indicators of bronchopulmonary dysplasia. This was an observational cohort of preterm infants born at a gestational age ≤32 + 6 weeks and with a body weight ≤2000 g. Amino acid and carnitine profiles were measured in dried blood spots (DBSs) during the early nutrition transitional phase using tandem mass spectrometry. Bronchopulmonary dysplasia was defined as oxygen dependence at 36 weeks of postmenstrual age or 28 days after birth. Metabolomic analysis was employed to define metabolites with significant differences, map significant metabolites into pathways, and identify metabolic indicators of bronchopulmonary dysplasia. We evaluated 45 neonates with and 40 without bronchopulmonary dysplasia. Four amino acids and three carnitines showed differences between the groups. Three carnitines (C0, C2, and C6:1) were high in the bronchopulmonary dysplasia group mostly; conversely, all four amino acids (threonine, arginine, methionine, and glutamine (Gln)) were low in the bronchopulmonary dysplasia group. Pathway analysis of these metabolites revealed two pathways with significant changes (p < 0.05). ROC analysis showed Gln/C6:1 at total parenteral nutrition phase had both 80% sensitivity and specificity for predicting the development of bronchopulmonary dysplasia, with an area under the curve of 0.81 (95% confidence interval 0.71-0.89). Amino acid and fatty acid metabolite profiles changed in infants with bronchopulmonary dysplasia after birth during the nutrition transitional period, suggesting that metabolic dysregulation may participate in the development of bronchopulmonary dysplasia. Our findings demonstrate that metabolic indicators are promising for forecasting the occurrence of bronchopulmonary dysplasia among preterm neonates.

In the summer of 2019, field measurements of ozone (O 3 ) and its precursors[volatile organic compounds (VOCs) and nitrogen oxides (NO x )] were carried out at an urban site in Ji'nan. We found that the daily maximum 8-hour averages φ (O 3 ) were (103.0±14.5)×10 -9 . The average φ (NO x ) and φ (VOCs), which are ozone precursors, were (16.7±11.3)×10 -9 and (22.4±9.4)×10 -9 , respectively. The ·OH reactivity of VOCs was determined (9.6±3.8) s -1 . Ji'nan suffered from serious O 3 pollution. An observation-constrained chemical box model was deployed to evaluate in situ photochemical O 3 production, which indicated that chemical reactions made positive contributions to O 3 production rates between 07:00 and 19:00 LT, with the average hourly O 3 production rate of 35.6×10 -9 h -1 . To evaluate the effectiveness of various ozone precursor control strategies in reducing ozone pollution, we combined the observation-based model (OBM) with the relative incremental reactivity (RIR) method. The key indicators that affect the local ozone production rate were identified. Ji'nan was under VOC-limited conditions and the key VOC precursors were alkenes. The O 3 formation mechanism changed from the VOC-limited regime in the morning to the transitional regime in the afternoon. Correspondingly, the simulated local O 3 production rate was increased from 18.3×10 -9 h -1 to 29.6×10 -9 h -1 . To further explore the role of anthropogenic emissions in ozone pollution, we used the positive matrix factorization (PMF) model to identify the major sources contributing to VOCs. The major sources in Ji'nan were vehicular exhaust and gasoline evaporation, accounting for more than 50% of the observed VOCs. Therefore, constraints on vehicular emissions is the most effective strategy to control O 3 pollution in Ji'nan.

Baicalin is a plant-derived flavonoid from Scutellaria baicalensis Georgi with multiple bioactivities and has a protective effect against avian pathogenic Escherichia coli (APEC) infection. However, the underlying mechanism of baicalin against APEC infection is still unknown. Therefore, we aimed to explore whether the protective effects and mechanisms of baicalin on APEC-induced lung inflammation were related to the regulation of gut microbiota. The results showed that baicalin significantly reduced APEC colonization and pro-inflammatory cytokines production, and additionally recovered air-blood barrier integrity in the lungs after APEC challenge. However, depletion of gut microbiota significantly weakened the protective effects of baicalin against APEC infection as mentioned above. Furthermore, baicalin markedly restored the dysbiosis of gut microbiota induced by APEC as well as increased the abundance of short chain fatty acid (SCFA)-producing bacteria and the production of SCFAs including acetic acid, propionic acid and butyric acid, especially acetic acid. In addition, the concentrations of acetic acid and its receptor free fatty acid receptor 2 (FFAR2) were significantly upregulated in the lung tissues after baicalin treatment. In conclusion, gut microbiota played a key role in the pharmacological action of baicalin against APEC-induced lung inflammation. Baicalin remodeled the dysbiosis of gut microbiota caused by APEC and increased the production of SCFAs, especially acetic acid in the gut, and then the increased acetate may circulate to the lungs to activate FFAR2 to defend APEC infection. Together, our study suggested that baicalin inhibited APEC infection through remodeling the gut microbiota dysbiosis and increasing the SCFA production. Furthermore, baicalin may serve as an alternative antibiotic and a novel therapeutic drug to prevent or treat APEC infection.

Background: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo., Methods: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MβCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo., Results: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects., Conclusions: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects., (© 2021. The Author(s).)

Chicken colibacillosis is caused by avian pathogenic Escherichia coli (APEC), and results in huge economic losses to the poultry industry. With the investigation of the gut-lung axis, more studies have demonstrated the important role of gut microbiota in lung inflammation. The precise role of the gut microbiota in chickens-associated colibacillosis, however, is unknown. Thus, this study assessed the function of the gut microbiota in the chicken defense against APEC infection. Chicken gut microbiota was depleted by drinking water with a mixture of antibiotics (Abx), and subsequently, a model of colibacillosis was established by the intranasal perfusion of APEC. The results showed that gut microbiota protects the chicken challenge by APEC from aggravated lung histopathologic injury, up-regulated pro-inflammatory cytokine production, and increased bacterial load in lung tissues compared with controls. In addition, the air-blood barrier permeability was significantly increased in gut microbiota-depleted chickens compared to the control chickens after challenge with APEC. Furthermore, feeding acetate significantly inhibited the lung inflammatory response and the reduced air-blood permeability induced by APEC infection. The expression of free fatty acid receptor 2 (FFAR2), a receptor for acetate, was also increased in the lung after treatment with acetate. In conclusion, depletion of the gut microbiota resulted in increased susceptibility of chickens to APEC challenge, and gut microbiota derived acetate acted as a protective mediator during the APEC challenge. Novel therapeutic targets that focus on the gut microbiota may be effective in controlling colibacillosis in poultry., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A six-day ozone pollution episode in Guangzhou in early October 2018 was analyzed with the application of a Lagrangian photochemical trajectory model to trace the sources of ozone, quantify the contributions of different regions, and evaluate the effects of emission reduction measures targeted at different emission sectors and different precursors on ozone pollution. The results showed that during the ozone pollution episode, the maximum daily 8 h ozone exceeded 160 μg·m -3 and the highest value reached 271 μg·m -3 . The average concentrations of nitrogen oxides and volatile organic compounds (VOCs) were (77.7±42.8) μg·m -3 and (71.9±56.2) μg·m -3 , respectively. Aromatics and alkenes were the dominant reactive VOCs, with contributions of 38% and 30% to·OH reactivity and 51% and 16% to ozone formation potential, respectively. The ozone pollution in Guangzhou during this episode was affected by three types of air masses, with the primary source regions of Guangzhou, Guangdong Province, and regions outside Guangdong Province. For all three air mass types, ozone production in these source region was controlled by VOCs. Sensitivity tests showed that, in the primary source regions, reducing the emissions of VOCs is more effective than reducing NO x in terms of reducing ozone concentrations. Under the condition of full emission reduction, regulating traffic emissions could substantially reduce ozone levels by 14.6%-21.0% in Guangzhou, which was a more significant reduction than regulating controlled industry (8.4%-15.3%), power plant (0.9%-6.2%) and residential (2.3%-4.7%) emissions. However, the traffic emission reduction is not as effective (induced ozone reduction<10%) when the emissions reduction ratio is lower than 90%. In addition, biogenic emissions in the Pearl River Delta also substantially contributed to the ozone levels under certain circumstances, as indicated by the ozone reduction up to 19% when biogenic emissions were shut off.

Aim: To analyze differences in ultra-widefield fluorescein angiography (UWFA) findings between dynamic and static images of eyes with diabetic retinopathy (DR)., Methods: This cross-sectional study included 28 eyes of 28 patients with DR undergoing UWFA. A series of UWFA images acquired from each patient were converted into a time-lapse video and used as a dynamic image. A single, clear, arteriovenous phase image was chosen as a static image. Non-perfusion index (NPI) and its correlation with vascular abnormalities in different zones were compared between dynamic and static UWFA imaging., Results: NPI appeared to increase from the center to the far-periphery in both groups. Dynamic NPI was lower in the total retinal area (0.26 vs 0.29, P =0.009) and far-periphery (0.33 vs 0.36, adjusted P =0.042), which was contrary to the static NPI. Far-peripheral NPI was associated with intraretinal microvascular abnormality in the posterior area in both groups., Conclusion: Time-lapse dynamic UWFA imaging is a useful modality to differentially diagnose hypofluorescence in the most peripheral region. This modality could provide a reliable method for NPI measurement., (International Journal of Ophthalmology Press.)

Objective: To investigate the protective effects and mechanisms of sesamin (SES) on dextran sulfate sodium (DSS)-induced experimental colitis in mice., Methods: SES (50, 100, and 200 mg kg-1) were orally administered to C57BL/6 male mice after DSS instillation. The anti-inflammatory effect of SES on colonic damage was assessed by clinical, macroscopic, microscopic, and inflammatory signaling pathways., Results and Conclusions: It could be found that bodyweight and colon length of mice treated with DSS was significantly decreased while that were increased by SES treatment. SES treatment reduced the DAI values and improved the histopathology of the colon in the DSS-treated mice. SES also reduced TNF-α, IL-1β and IL-6 production caused by DSS. We also measured the expression of the phosphorylation of p65, IκB, p38, ERK and JNK protein and found that SES can alleviate colon damage via the NF-κB and MAPK signaling pathways. The findings of this study suggested that SES had anti-inflammatory effects on intestinal inflammation and can be used as a new therapeutic candidate for inflammatory bowel disease.

Acute liver injury can be caused by chemicals and can lead to liver failure. We investigated the protective effect of helicid (HEL) on acute liver injury caused by CCl 4 in mice. We found that ALT and AST levels as well as hepatic pathological damage in mice treated with CCl 4 was increased significantly, while the effects were decreased by HEL treatment. HEL treatment increased the activity of T-SOD, GSH and CAT and reduced the level of MDA in CCl 4 treated mice. HEL improved the histopathology of liver caused by CCl 4 . HEL also reduced TNF-α, IL-1β and IL- 6 activity caused by CCl 4 . We investigated the phosphorylation of p65 and IκB protein and found that HEL can alleviate liver damage via the NF-κB signaling pathway. Our findings indicate that HEL protects against acute liver injury induced by CCl 4 . The protective effect of HEL appears to be due to its antioxidative and anti-inflammatory properties through the NF-κB signaling pathway.

Madecassoside (MA), a crucial ingredient of Centella asiatica , has been reported to exhibit a variety of bioactivities, including antipulmonary fibrosis, and antiinflammatory effects. Here we aimed to elucidate the protective effects and underlying mechanisms of MA on LPS-induced acute lung injury (ALI). The mice were treated with MA for one week and then received intratracheal of LPS to establish the ALI model. Then we evaluated the pathological changes by haematoxylin and eosin staining and measured the levels of proinflammatory cytokines and myeloperoxidase (MPO) by ELISA, the transcriptional level of tight junction proteins by qRT-PCR, as well as the expression of Toll-like receptor4/Nuclear factor kappa-B (TLR4/NF-κB) pathway by Western blot. The results showed that MA significantly inhibited LPS-induced pathological damages, lung edema, MPO, and proinflammatory cytokines production. Furthermore, MA obviously repaired alveolar epithelium integrity showing by reduced secretion of total proteins in the BALF and enhanced mRNA expression of tight junction as Occludin and zonula occludens-1 (ZO-1) comparing to LPS. Further research showed that LPS stimulation activated the TLR4/NF-κB signaling pathway and the activation was inhibited by MA. In conclusion, these data indicated that MA had protective effects against LPS-induced ALI. The therapeutic mechanisms may be associated with reducing the alveolar epithelium permeability and inflammatory response via repressing the activation of TLR4/NF-κB pathway., (Copyright © 2020 Peng, Shi, Yuan, Li, Song, Huang, Yi, Shen and Fu.)

Avian pathogenic Escherichia coli (APEC) is a kind of highly pathogenic parenteral bacteria, which adheres to chicken type II pneumocytes through pili, causing inflammatory damage of chicken type II pneumocytes. Without affecting the growth of bacteria, anti-adhesion to achieve anti-inflammatory effect is considered to be a new method for the treatment of multi-drug-resistant bacterial infections. In this study, the anti-APEC activity of schizandrin was studied in vitro. By establishing the model of chicken type II pneumocytes infected with APEC-O78, the adhesion number, the expression of virulence genes, the release of lactate dehydrogenase (LDH), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were detected. The results showed that schizandrin reduced the release of LDH and the adherence of APEC on chicken type II pneumocytes. Moreover, schizandrin markedly decreased the levels of IL-1β, IL-8, IL-6, and TNF-α, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings revealed that schizandrin could reduce the inflammatory injury of chicken type II pneumocytes by reducing the adhesion of APEC-O78 to chicken type II pneumocytes. The results indicate that schizandrin can be a potential agent to treat inflammation caused by avian colibacillosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats., Materials and Methods: Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490)., Results: At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F 2t -isoprostane, thromboxane B 2 , and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO., Conclusions: The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To observe the effect of the "head-nine-needle" therapy on tension headache., Methods: A total of 150 patients with tension headache were divided into a head-nine-needle therapy group, a western medicine control group and an acupuncture control group according to the random number table, 50 cases in each one. In the head-nine-needle therapy group, the head-nine-needle therapy was adopted. In the western medicine control group, epiperisone hydrochloride tablets were prescribed for oral administration, 50 mg, three times a day as well as fluoguili hydrochloride capsules, 5 mg, once a day, taking orally before sleep. In the acupuncture control group, the routine acupuncture technique was used at Baihui (GV20), Taiyang (EX-HN5), Fengchi (GB20) and Ashi (extra), etc. The clinical effect was observed in each group. The scores of visual analogy scale (VAS) for headache severity and the scores of headache duration were assessed before and after treatment in the patients of each group., Results: In comparison of the total effective rate among the groups, there was no significant difference between the head-nine-needle therapy group (48/50，96.0%) and the acupuncture control group (47/50，94.0%). The total effective rate of either of the two groups was higher than that of the western medicine control group (40/50，80.0%， P <0.05). The VAS score and the score of headache duration were reduced obviously as compared with those before treatment in each group ( P <0.05), and the score was not different significantly between the head-nine-needle therapy group and the acupuncture control group ( P >0.05). After 3 weeks and 4 weeks of treatment, the scores in the two acupuncture groups were all better than those in the western medicine control group ( P <0.05)., Conclusion: The "head-nine-needle" therapy achieves the obviously advantages in the alleviation of headache degree as compared with the simple western medicine and its effect is similar to the common acupuncture therapy in the patients with tension headache.

Avian pathogenic Escherichia coli (APEC) can cause serious pathological changes and inflammation in chickens. Schizandrin has anti-inflammatory activity and can prevent damage to various tissues and organs. The purpose of this study was to investigate the protective effect of schizandrin on APEC-induced lung lesions in chickens and explore the potential mechanism of schizandrin protection. The schizandrin (50, 100, and 200 mg/kg) was intragastrically administered for 3 days. APEC was administered using intraperitoneal (i.p.) injection to induce lung lesions. Then, chickens were sacrificed by CO 2 inhalation 24 h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA), levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Our findings showed that schizandrin markedly inhibited pathological changes, pulmonary edema, MPO activity and MDA content. Moreover, schizandrin markedly reduced the levels of TNF-α, IL-1β, IL-6 and IL-8 in lung tissue. Importantly, the mechanism responsible for these effects was attributed to the inhibitory effect of schizandrin on NF-κB and MAPK signaling activation. In conclusion, our findings reveal that schizandrin displays anti-oxidant and anti-inflammatory activity against APEC-induced lung lesions in chickens, paving the way for rational use of schizandrin as a protective agent against lung-related inflammatory disease., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The study aimed to detect and analyze long non-coding RNAs (lncRNAs) in plasma of children diagnosed with chronic gastritis, and to explore its biological functions and involved signaling pathways., Methods: The plasma samples were collected from six children that were diagnosed with chronic gastritis by physical examination, gastroscopy, and pathological examination and six healthy children. The plasma samples were assayed for determining the expression profiles of lncRNA based upon the gen chip detection. The specific expression of lcnRNA in plasma of children with chronic gastritis was analyzed and its biological functions were speculated., Results: Five lncRNAs ( RP11-697M17.1 , RP11-388M20.9 , AFAP1-AS1 , BC062758 , and XLOC001406 ) were significantly up-regulated, and five lncRNAs ( UNQ697 , BX571672.5 , CYP4F35P , ANKRD20A5P , and AL832737 ) were observed to be significantly down-regulated. The lncRNAs RP11-697M17.1, and UNQ697 were detected with the highest up-regulation and down-regulation, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the up-regulated lncRNAs were significantly enriched in 20 signaling pathways such as phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) pathway, and the down-regulated lncRNAs target genes were significantly enriched in 20 signaling pathways such as the metabolic pathway., Conclusion: The analysis of the lncRNA expression profiles in plasma of children with chronic gastritis revealed that the lncRNA RP11-697M17.1, and lncRNA UNQ697 may act as plasma markers for predicting chronic gastritis in children., (© 2020 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Acute lung injury (ALI) is a common and complex inflammatory lung syndrome with higher morbidity and mortality rate. Piceatannol (PIC) has anti-inflammation and anti-oxidant properties. The study was designed to explore the effect and the action mechanisms of PIC on lipopolysaccharide (LPS)-induced ALI. Twenty-four hours after LPS challenge, mice from different treatment groups were euthanized, and the bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. Then the degree of pulmonary edema, lung pathological changes, myeloperoxidase (MPO) activity, and the production of pro-inflammatory cytokines were detected. Additionally, the messenger RNA (mRNA) expressions associated with cell adhesion molecules and tight junction were analyzed through quantitative real-time (qRT)-PCR, and the TLR4/NF-κB activation was examined by western blot. The results showed that PIC significantly inhibited LPS-induced lung edema, histopathological damage, MPO activity, cell infiltration, and pro-inflammatory cytokines production. Moreover, PIC notably suppressed mRNA expressions associated with inflammation and cell adhesion molecules. Furthermore, PIC also alleviated LPS-induced damage of air-blood barrier through reducing the levels of total proteins in BALF and recovering the expression of occludin and ZO-1 in the lung tissues. We also found that PIC remarkably restrained the LPS-induced TLR4/NF-κB pathway activation in lung tissues. In conclusion, PIC may be potential to treat LPS-induced acute lung injury (ALI) via regulating air-blood barrier and TLR4/NF-κB signaling pathway activation., (Copyright © 2020 Peng, Yuan, Shi, Li, Song, Huang, Yi, Fu and Shen.)

The construction of chiral multiple-substituted cyclohexanes motifs is a challenging topic in organic synthesis. By the combination of desymmetrization and remote stereocontrol, a ruthenium-catalyzed transfer hydrogenative desymmetrization of 2,2,5-trisubstituted 1,3-cyclohexanediones has been successfully developed for the construction of chiral multiple-substituted cyclohexanes with high enantioselectivity and diastereoselectivity. When an ester group was introduced to the two-position, a hydrogenative desymmetrization/transesterification cascade occurred, affording the bicyclic lactones bearing three stereocenters, including two discrete stereocenters and one quaternary stereogenic center, with high enantioselectivity. The products are the multiple-substituted chiral cyclohexanes bearing the hydroxyl and carbonyl functional groups, which provide a new opportunity for further precise elaboration.

Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: A growing body of evidence has found links between endocrine disruptor phthalates and male reproductive disorders, but the mechanisms underlying these relationships are poorly known. Seminal plasma metabolomes may mediate associations of phthalate exposure with impaired semen quality., Objective: To identify seminal plasma metabolomes associated with poor semen quality and evaluate their associations with urinary phthalate metabolites among 660 Chinese adult men., Method: The seminal plasma metabolic profiles were acquired using an untargeted approach based on liquid chromatography-high resolution mass spectrometry. We explored the differences in seminal plasma metabolites between participants with poor and good semen quality and evaluated cross-sectional associations between discriminatory metabolic biomarkers and urinary phthalate metabolites., Results: Differences between poor and good semen quality groups were observed in relation to 25 seminal plasma metabolites, mostly related to the metabolism of polyunsaturated fatty acids (PUFA) and acylcarnitine (all p < 0.05). After adjusting for various confounders and multiple tests, metabolites were all significantly associated with one or more individual sperm quality parameters (motility, concentration, total count, and morphology) (all p < 0.05). Among identified metabolic biomarkers, seminal plasma L-palmitoylcarnitine, linoelaidyl carnitine, and oleic acid were inversely associated with urinary mono-(2-ethylhexyl) phthalate (MEHP), and seminal plasma L-acetylcarnitine was inversely associated with the proportion of di-(2-ethylhexyl)-phthalate metabolites (DEHP) excreted as MEHP in urine (%MEHP) (all p < 0.05). Mediation analysis revealed that oleic acid and L-acetylcarnitine mediated significant proportions (6.7% and 17%, respectively) of the positive associations between urinary DEHP metabolites and the percentage of spermatozoa with an abnormal head., Conclusions: Elevated urinary phthalate metabolites may impact semen quality by causing metabolic disorders of seminal plasma PUFAs and acylcarnitine. These pathways warrant further investigation., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bacterial pneumonia is a leading cause of death in the animal husbandry. Acute lung injury (ALI), most often seen as a part of systemic inflammatory process, characterized by progressive hypoxemia, edema, and neutrophil accumulation in the lung. Baicalin has been reported to inhibit inflammatory response, but its role in ALI remains unknown. The purpose of our study was to determine the protective effect and possible mechanism of baicalin against avian pathogenic Escherichia coli (APEC)-induced ALI in chicken. Chickens were conditioned with baicalin 1 week before intratracheally instilled with APEC. Then, chickens were sacrificed by CO 2 inhalation 12 h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, levels of pro-inflammatory cytokines and activation of NF-κB signaling pathway. The results showed that pre-treatment of chickens with baicalin significantly alleviated the death rate, histopathological changes in lung tissues. The W/D ratio, MPO activity and production of cytokines, such as IL-1β, TNF-α, IL-6 of lung tissues were also decreased following treatment with baicalin. Furthermore, the mechanism responsible for these effects was attributed to the inhibitory effect of baicalin on nuclear factor-κB (NF-κB) signaling activation. These data thus support the application of baicalin as a potential medicine for the treatment of E. coli-induced ALI by regulating NF-κB signaling pathway., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Avian pathogenic Escherichia coli (APEC) causes great economic loss to the poultry industry worldwide. Chicken type II pneumocytes (CP II cells) secrete surfactants and modulate lung immunity to decrease the infection of the invading pathogen. Nevertheless, the pathogenesis of CP II cells to APEC infection remains poorly understood. Therefore, we conducted global gene expression profiling of CP II cells after APEC-O78 infection to explore the host-pathogen interaction. The differentially expressed genes of CP II cells to APEC infection were characterized by RNA-seq with EB-seq algorithm. In consequence, the mRNA of 18996 genes was identified, and CP II cells responded to APEC infection with marked changes in the expression of 1390 genes. Among them, there are 803 down-regulated mRNAs and 587 up-regulated mRNAs. The KEGG prediction and Gene Ontology terms analysis revealed that the major enriched pathways were related to NF-κB signaling pathway, apoptosis pathway, tight junction, and cytokine-cytokine receptor interaction and other pathways. We adopted qRT-PCR to verify the validity of the selected gene expression. The fold induction of qPCR was similar to the RNA-seq results. These results provide a better understanding of the pathogenesis of APEC, especially apoptosis pathway involved in APEC infection., Competing Interests: The authors have declared that no competing interests exist.

Background: Canine distemper virus (CDV) can cause a highly contagious disease to canid. However, how CDV affects peripheral blood lymphocyte (PBL) remains unclear., Methods: In this study, CDV infected PBL was cultured to investigate the effect of CDV on the differentiation of lymphocytes and the mRNA expression of inflammatory cytokines in PBL., Results: The results showed that CDV changed the phenotype of lymphocytes and increased the percentage of CD4 + CD8 + T cells. To explore the effect of immune response of lymphocytes to CDV, the mRNA expression of pro- and anti-inflammatory cytokines was examined. Interleukin (IL-6, IL-12B), and tumor necrosis factor (TNF)-α mRNA expression was significantly increased at 12-48 h after CDV infection. IL-10 mRNA expression was dramatically enhanced at 12-36 h after CDV infection. However, IL-4 and transforming growth factor (TGF-β) were not response to CDV infection. These results indicated that PBL differentiated intoCD4 + CD8 + T cells and improved the inflammatory response to CDV infection., Conclusions: After CDV infection, PBL differentiated into CD4 + CD8 + T cells and initiated inflammatory response., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Axially chiral biimidazole ligands have been rarely synthesized and studied, in contrast to the significant achievements in the synthesis and application of central chiral imidazole ligands. Herein, a series of novel axially chiral 2,2'-biimidazole ligands were synthesized from the reaction of 2,2'-bis(bromomethyl)-1,1'-binaphthalene and 2,2'-biimidazole in one step through the strategy of remote chirality delivery. These ligands have been proven to be efficient for Cu- or Fe-catalyzed asymmetric insertion of α-aryl-α-diazoacetates into the N-H bond of carbazoles with up to 96% ee.

Avian pathogenic Escherichia coli (APEC), collectively known as causative agent of extraintestinal infections, is an important cause of morbidity and mortality in poultry. Currently, quorum sensing (QS), biofilm formation and virulence factors are considered as novel prospective targets for antimicrobial therapy to control APEC invasion. In addition, inflammatory responses are also served as the major pathological features of APEC invasion. This study was aimed to explore the effect of baicalin on APEC and APEC-induced inflammatory responses. After treatment with baicalin, we mainly examined the AI-2 secretion, biofilm formation, expression of virulence genes of APEC, and the levels of inflammatory cytokines, as well as the expression of NF-κB pathway. Our results showed that baicalin significantly inhibited the QS via decreasing the AI-2 secretion, biofilm formation, and the expression of virulence genes of APEC such as LsrB, LsrK, LuxS, pfs, H-NS, fimA, fimB, fyuA, csgA, csgB, and rpoS. Moreover, baicalin significantly attenuated the release of lactate dehydrogenase (LDH), and the adhesion of APEC to chicken type II pneumocytes to reduce cell damage. Furthermore, baicalin also inhibited the expression of pro-inflammatory cytokines and NF-κB activation. Thus, our data revealed that baicalin could interfere with the quorum sensing, biofilm formation and virulence genes expression to relieve the APEC pathogenicity. Additionally, baicalin decreased the inflammatory responses of chicken type II pneumocytes induced by APEC. Taken together, these data provide a novel potential pharmaco-therapeutic approach to chicken colibacillosis.

Objective: To summarize the clinical data including manifestations, diagnosis, treatment and prognosis of eosinophilic gastroenteritis (EGE) in children. Methods: A retrospective analysis was performed in 71 patients with pathologically proven EGE at Beijing Children's Hospital Affiliated to Capital Medical University from January 2008 to January 2017. Their clinical manifestations, laboratory and imaging examinations, endoscopic findings, histopathological examinations, and treatment were collected and analyzed. Results: Among 71 EGE cases, 47 (66%) cases were male and 24 (34%) cases were female, and the median age was 9.2 (0.2-16.5) years old. The main clinical manifestations included abdominal pain (76%, 54/71), vomiting (68%, 48/71), anorexia (54%, 38/71), weight loss (38%, 27/71), and diarrhea (37%, 26/71). There were 27 cases (38%) with a history of allergic diseases or family history. The median absolute value of eosinophil in peripheral blood of the 71 patients was 0.4 (0-36.8)×10(9)/L, and 27 cases (38%) showed an increase in eosinophil counts. Serum IgE was measured in 52 patients (104.3 (3.4- 3 000.0)×10(3) U/L), and 30 patients (58%) showed an increase in serum IgE. A large number of eosinophils ((41.0±8.5)/HP) were found in 3 patients' ascites. The endoscopic examination of upper gastrointestinal tract revealed hyperemic edema in 62 cases (87%), plaque in 44 cases (62%), erosion in 17 cases (24%) and ulceration in 16 cases (23%). Histopathologically, in 8 cases (11%) the disease involved both stomach and duodeneum, in 21 cases (30%) involved stomach only, and in 37 cases (52%) involved duodeneum only. In addition, in 6 cases (8%) the disease involved esophagus and in 10 cases (14%) involved colorectum. Microscopically, eosinophil counts averaged 67/HP, 33/HP, 40/HP and 38/HP in esophageal, gastric, duodenal and colorectal mucosa respectively. A total of 34 cases were treated with glucocorticoid, and all these patients had alleviation of symptoms, which occurred within 14.9 days on average, but EGE recurred in 11 cases (32%). Conclusions: The clinical symptoms and endoscopic findings of EGE are diverse and nonspecific. Histopathological examination of gastrointestinal mucosa is particularly important for the diagnosis. Glucocorticoid treatment is effective, but the patients with EGE are prone to relapse.

The first highly enantioselective hydrogenation of carbocyclic aromatic amines has been successfully realized using in situ-generated chiral ruthenium complex as catalyst, affording facile access to chiral exocyclic amines with up to 98% ee.

Objective: To analyze the clinical manifestations, diagnosis, treatment and prognosis of intestinal lymphangiectasia (IL) in children in order to improve the skills of diagnosis and treatment of IL. Method: Clinical manifestations, laboratory findings, gastroscopic findings, histopathological examinations and lymphatic radionuclide imaging assessments were analyzed retrospectively among 47 IL patients who were hospitalized in the Gastroenterology Department of Beijing Children's Hospital Affiliated to Capital Medical University from June 2007 to December 2015. All patients were followed up by telephone. According to the various causes, the patients were divided into the primary intestinal lymphangiectasia (PIL) group and secondary IL group, and their clinical manifestations were compared by t test, Rank sum test or Chi-square test. Result: In 47 IL patients, there were 38 children (81%) younger than 3 years old. There were 43 PIL patients (91%) and 4 secondary IL patients (9%). Between PIL and secondary IL, there were statistical differences in serum albumin ( t=- 3.950, P< 0.005) , globulin( t=- 2.850, P= 0.007), age of onset( U =27.000, P= 0.024), age at diagnosis( U =29.000, P= 0.030) and course of disease( U =26.500, P= 0.023), whereas there were no statistical differences in lymphocyte count, IgG, lymphatic radionuclide imaging, histopathology and gender(all P> 0.05). Edema (44 cases, 94%), diarrhea (42 cases, 89%), accompanied with infection (35 cases, 74%) and ascites (30 cases, 64%) were the main clinical manifestations. In 47 IL patients, 45 patients were done gastroscopy and histopathological examinations, and there were 31 patients' histopathological examinations(69%) were positive. Forty patients were done lymphatic radionuclide imaging, and there was evidence of protein losing from gut via lymphatic radionuclide imaging in 39 patients(98%). Among 47 patients, 35 patients (74%) were followed up, 32 patients had good prognosis, 2 patient failed to show evidence of improvement, 1 patient died and no patient experienced a relapse till the end of the follow-up. In 35 patients, 28 patients were treated with medium chain triglycerides (MCT) dietary therapy, 26 patients showed improvement in symptoms, and 2 patients had no improvement. Among 35 patients with follow-up, there were 6 patients received surgical treatment, and their symptoms were improved. Conclusion: PIL are the majority of IL in children younger than 3 years old. The main clinical manifestations are edema, diarrhea, accompanied with infection and ascites. For the patients without the evidence of lymphangiectasia from duodenum histopathological examination, further consideration of lymphatic radionuclide imaging, clinical manifestations, and laboratory studies are needed to make a final diagnosis. MCT dietary therapy is the cornerstone of IL medical management.

Objective: The dysregulation of proliferation and apoptosis plays a significant role in the pathogenesis of hormone-induced osteonecrosis of femoral head (ONFH). The research aimed to explore the regulatory role of miR-146a in dexamethasone (DEX)-induced proliferation and apoptosis change in MC3T3-E1 cells from murine osteoblastic., Material and Methods: In this study, MC3T3-E1 was co-cultured with 10-7 DEX for 6 h, then RT-PCR was employed to test the expression level of miR-146a and Bcl2. CCK8 assay and flow cytometry were adopted to verify miR-146a could regulate proliferation and apoptosis. After transfected MC3T3-E1 with mimics and inhibitor, RT-PCR and Western blot was used to detect Bcl2 expression level., Results: In DEX treated MC3T3-E1 cells showed higher MiR-146a expression level and lower Bcl2 expression level. MiR-146a could inhibit proliferation and promotes apoptosis in murine osteoblastic MC3T3-E1 cells. Additionally, Bcl2 gene is regulated by MiR-146a., Conclusions: The MiR-146a expression level increased, while Bcl2 has low expression level in dexamethasone treated MC3T3-E1 cells. MiR-146a regulates proliferation and apoptosis of mouse bone cells. The low expression level of Bcl2 in DEX treated MC3T3-E1 cells is caused by increased MiR-146a level.

Canine distemper (CD) is a highly contagious disease caused by the canine distemper virus (CDV), and mortality can be as high as 100%. However, there is no specific treatment for CD. In this study, the antiviral activity of the caffeic acid against CDV was evaluated in vitro. The results showed that the IC 50 of the caffeic acid against CDV at 1 and 2 h post infection (PI) is 23.3 and 32.3 μg/mL, respectively. Consistently, at 1 and 2 h PI, the caffeic acid exhibited a reduced (23.3-57.0% and 37.2-38.1%) viral inhibitory effect in vero cells. Furthermore, the caffeic acid plus Ribavirin (RBV) has greater antiviral activity against CDV than the caffeic acid or RBV individually. In addition, the caffeic acid reduced the total viral RNA synthesis by 59-86% at 24-72 h. Therefore, our data provided the experimental evidence that the caffeic acid effectively inhibited CDV infection in vero cells, which may potentially be used to treat clinical disease associated with CDV infection., (Copyright © 2017. Published by Elsevier Ltd.)

C-terminus kinesin motor KIFC1 is known for centrosome clustering in cancer cells with supernumerary centrosomes. KIFC1 crosslinks and glides on microtubules (MT) to assist normal bipolar spindle formation to avoid multi-polar cell division, which might be fatal. Testis cancer is the most common human cancer among young men. However, the gene expression profiles of testis cancer is still not complete and the expression of the C-terminus kinesin motor KIFC1 in testis cancer has not yet been examined. We found that KIFC1 is enriched in seminoma tissues in both mRNA level and protein level, and is specifically enriched in the cells that divide actively. Cell experiments showed that KIFC1 may be essential in cell division, but not essential in metastasis. Based on subcellular immuno-florescent staining results, we also described the localization of KIFC1 during cell cycle. By expressing ΔC-FLAG peptide in the cells, we found that the tail domain of KIFC1 might be essential for the dynamic disassociation of KIFC1, and the motor domain of KIFC1 might be essential for the degradation of KIFC1. Our work provides a new perspective for seminoma research., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Mycoplasma pneumoniae (M. pneumoniae) infection can cause community acquired pneumonia in children. A real-time method of simultaneous amplification and testing of M. pneumoniae (SAT-MP) was developed to diagnose M. pneumoniae targeting a region of the ribosomal RNA. The SAT-MP assay can accurately identify M. pneumoniae with a detection range from 101 to 107 CFU/ml. In this study, the specimens from 315 children with pneumonia were collected and analyzed by SAT-MP in parallel with real-time PCR method and IgM ELISA assay. The positive rates of these specimens examined by SAT-MP assay, real-time PCR method and IgM ELISA assay were 16.51%, 15.56% and 12.70% respectively. While there was statistical significance (p = 0.04) between SAT-MP assay and IgM ELISA assay, no statistical significance (p = 0.25) was found between SAT-MP assay and real-time PCR method and these two methods had high consistency (kappa value = 0.97). These findings indicate that the newly developed SAT-MP assay is a rapid, sensitive and specific method for identifying M. pneumoniae with potential clinical application in the early diagnosis of M. pneumoniae infection.

Objective: To increase the recognition of pancreatic cystic fibrosis (PCF) in children and facilitate diagnosing and treatment of this rare entity. Method: This is a retrospective analysis of children who presented to Beijing Children's Hospital affiliated to Capital Medical University from January 2010 to December 2015. We describe their clinical features, laboratory testing and management. Result: Eleven children were diagnosed with PCF by genetic testing or sweat chloride test during these 5 years, including 4 boys and 7 girls. Their age ranged from 0.5-14.3 (mean 9.0±3.9) years. Family history was positive in 3 children. Significant clinical findings on presentation were: malnutrition 6, including 2 cases of mild, moderate and severe malnutrition each; diarrhea 4 (yellow mushy or watery stool with frequency ranging from 2-5 times a day), including 1 case of acute diarrhea and 3 of chronic diarrhea, 3 of them had steatorrhea; abdominal pain 3. All of them had pancreatic lesions shown by abdominal ultrasound. Blood tests showed 6 cases had elevated serum amylase and lipase. The main treatment was pancreatic replacement therapy and nutritional support. Conclusion: PCF is rare in children. Malnutrition, diarrhea and abdominal pain are the main clinical manifestations. Treatment is mostly pancreatic enzymes replacement and supportive care.

KIF3b is a protein of the kinesin-2 family which plays an important role in intraflagellar transport. Testis cancer is a common cancer among young men. Its diagnostic rate is increasing and over half of the cases are seminomas. Many aspects of the mechanism and gene expression background of this cancer remain unclear. Using western-blotting and semi-quantitative PCR we found high protein levels of KIF3b enrichment in seminoma tissue despite the mRNA levels remaining equivalent to that of normal testicular tissues. The distribution of KIF3b was mainly in cells with division potential. Wound-healing assays and cell counting kit assays showed that the knockdown of KIF3b significantly suppressed cell migration ability, viability and number in HeLa cells. Immunofluorescence images during the cell cycle revealed that KIF3b tended to gather at the spindles and was enriched at the central spindle. This indicated that KIF3b may also have direct impacts upon spindle formation and cytokinesis. By counting the numbers of nuclei, spindles and cells, we found that the rates of multipolar division and multi-nucleation were raised in KIF3b-knockdown cells. In this way we demonstrate that KIF3b functions importantly in mitosis and may be essential to seminoma cell division and proliferation as well as being necessary for normal cell division., (Copyright © 2017 Elsevier Inc. All rights reserved.)

An iridium-catalyzed asymmetric hydrogenation/oxidative fragmentation of 6-substituted 5H-benzo[d] benzofuro[3,2-b]azepines has been developed, providing an efficient access to optically active 4-substituted 4,5-dihydro-1H-benzo[d]azepin-1-ones with up to 91% ee. A possible reaction pathway includes the asymmetric hydrogenation to furnish chiral cyclic amines and oxidative fragmentation under an air atmosphere.

Avian pathogenic Escherichia coli (APEC) infections are responsible for great losses in the poultry industry. Quorum sensing (QS) acts as a global regulatory system that controls genes involved in bacterial pathogenesis, metabolism and protein biosynthesis. However, whether QS of APEC is related to cell damage has not been elucidated. In the present study, we explored the correlation between the damage of chicken type II pneumocytes induced by APEC and the autoinducer-2 (AI-2) activity of APEC. The results showed that when chicken type II pneumocytes were co-cultured with 10 8  CFU/ml of APEC-O78 for 6 h, the release of LDH reached the highest level (192.5 ± 13.4 U/L) (P < 0.01), and the percentages of dead cells followed the same trend in trypan blue exclusion assay. In addition, the AI-2 activity of cell-free culture fluid (CF) reached the maximum value after 6 h co-culture with 10 8  CFU/ml of APEC-O78. At the same time, the mRNA expressions of eight virulence genes (papC, fimA, fimC, hlyE, ompA, luxS, pfs, and qseA) of 10 8  CFU/ml APEC-O78 were significantly increased compared with those of 10 7  CFU/ml, and the mRNA expressions of four virulence genes (hlyE, tsh, iss, and luxS) of 10 8  CFU/ml APEC-O78 were higher than those of 10 9  CFU/ml (p < 0.05) after incubation for 6 h. These results suggested that AI-2-mediated QS is involved in the cell damage induced by APEC-O78, indicating AI-2 may be one new potential target for preventing chicken colibacillosis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Avian pathogenic Escherichia coli (APEC) induces septicemia in chickens by invading type II pneumocytes after breaching the blood-air barrier. Type II pneumocytes play an important role in maintaining the function of the blood-air barrier. Astragaloside IV has been shown in previous studies to have an anti-inflammatory effect. To explore whether astragaloside IV can inhibit APEC-induced injury in chicken type II pneumocytes, cells were infected with APEC-O78. The results showed that astragaloside IV significantly reduced cell damage in chicken type II pneumocytes induced by APEC-O78 by downregulating the production of TNF-α and IL-1β, upregulating the secretion of IL-4 and IL-10, suppressing the mRNA levels of TLR-4, TLR-5, ERK, and p38 of chicken type II pneumocytes as well as inhibiting bacterial adhesion and F-actin cytoskeleton polymerization. These results suggest that astragaloside IV may be useful in novel pharmaco-therapeutic approaches to the treatment of chicken colibacillosis.

Cinobufagin (CBG), one active ingredient isolated from Venenum Bufonis, has been demonstrated to have immunoregulatory effect. The aim of this study was to investigate whether CBG can enhance the protective efficacy of formalin-inactivated Salmonella typhimurium (FIST) in mice. ICR mice were immunized with FIST (10 6  CFU/mouse) alone or mixed with CBG (10, 20, and 40 μg) or alum (200 μg) on day 1 and day 15. Two weeks after the second immunization, serum and spleen were sampled for measuring FIST-specific antibody levels, cytokine levels, and splenocyte proliferation. The results showed that CBG enhanced FIST-specific IgG and IgG2a, the levels of interferon-gamma (IFNγ) and nitric oxide (NO), and the splenocyte proliferation response induced by concanavalin A, lipopolysaccharide, and FIST. In vivo protection studies showed that CBG significantly decreased the bacterial burdens in the spleen and prolonged the survival time of FIST-immunized mice challenged with live Salmonella typhimurium. In vivo IFNγ neutralization led to a significant reduction in FIST-specific IgG2a and IFNγ levels, and in the protective efficacy in CBG/FIST-immunized mice. In conclusion, CBG enhances the protective efficacy of formalin-inactivated Salmonella typhimurium vaccine by promoting the Th1 immune response., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Duck Tembusu virus (DTMUV) has spread to the major duck-farming region in China, causing acute egg-production drop in Chinese duck population. In this study, we characterized a DTMUV strain (named GD2014) isolated from an egg-production drop duck farm in Guangdong province, South China. The virus was pathogenic to Muscovy duck embryos and caused severe egg production drop for laying Muscovy ducks. The genome sequence of GD2014 shared 97-99% homologies with other waterfowl-origin Tembusu viruses, and shared 89% identities with MM1775 strain isolated from mosquito. Phylogenetic analysis of entire open reading frame (ORF), E gene and NS5 gene indicated that GD2014 belonged to Ntaya group. These results have implications for understanding the orgin, emergence and pathogenicity of DTMUV as well as for the development of vaccines and diagnostics based on epidemiological data., (Copyright © 2016 Elsevier B.V. All rights reserved.)

This study investigated whether the rotavirus infection rate in children is associated with temperature and air pollutants in Hangzhou, China. This study applied a distributed lag non-linear model (DLNM) to assess the effects of daily meteorological data and air pollutants on the rotavirus positive rate among outpatient children. There was a negative correlation between temperature and the rotavirus infection rate. The impact of temperature on the detection rate of rotavirus presented an evident lag effect, the temperature change shows the greatest impact on the detection rate of rotavirus approximate at lag one day, and the maximum relative risk (RR) was approximately 1.3. In 2015, the maximum cumulative RR due to the cumulative effect caused by the temperature drop was 2.5. Particulate matter (PM) 2.5 and PM10 were the primary air pollutants in Hangzhou. The highest RR of rotavirus infection occurred at lag 1-1.5 days after the increase in the concentration of these pollutants, and the RR increased gradually with the increase in concentration. Based on the average concentrations of PM2.5 of 53.9 μg/m(3) and PM10 of 80.6 μg/m(3) in Hangzhou in 2015, the cumulative RR caused by the cumulative effect was 2.5 and 2.2, respectively. The current study suggests that temperature is an important factor impacting the rotavirus infection rate of children in Hangzhou. Air pollutants significantly increased the risk of rotavirus infection, and dosage, lag and cumulative effects were observed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We performed a prospective observational study to evaluate the utility of measuring inflammatory cytokine levels to discriminate bacterial meningitis from similar common pediatric diseases. Inflammatory cytokine levels and other cerebrospinal fluid (CSF) physicochemical indicators were evaluated in 140 patients who were diagnosed with bacterial meningitis via microbiological culture or PCR assay. The CSF concentrations of interleukin (IL)-6 and IL-10, CSF/blood IL-6 and IL-10 ratios, CSF white blood cell count, and CSF micro total protein were significantly elevated in bacterial meningitis patients compared with healthy children or patients with viral encephalitis, epilepsy, or febrile convulsions (P < 0.001). The area under the curve values for CSF concentrations of IL-6 and IL-10, CSF/blood IL-6 and IL-10 ratios, CSF white blood cell count, and CSF micro total protein to identify bacterial meningitis episodes by receiver-operating characteristic analysis were 0.988, 0.949, 0.995, 0.924, 0.945, and 0.928, respectively. The area under the curve for the combination of CSF IL-6 and CSF/blood IL-6 ratio was larger than that for either parameter alone, and the combination exhibited enhanced specificity and positive predictive value. After effective meningitis treatment, CSF IL-6 levels dropped significantly. These results suggest that CSF IL-6 and CSF/blood IL-6 ratio are good biomarkers in discriminating bacterial meningitis. Evaluating CSF IL-6 and CSF/blood IL-6 ratio in combination can improve diagnostic efficiency. Additionally, CSF IL-6 levels can be used to monitor the effects of bacterial meningitis treatment., Competing Interests: The authors have no conflicts of interest to disclose.

Background: To study the inhibition of retinoblastoma cell viability by two commonly used autophagy inhibitors, chloroquine (CQ) and 3-methyladenine (3-MA), alone or in combination with the conventional chemotherapeutic drug vincristine (VCR), and to investigate whether the mechanisms of these drugs are related to inhibition of autophagy., Methods: On retinoblastoma cell line HXO-Rb44, VCR, CQ and 3-MA were used individually or combined. The cell viability was determined by CCK8 method, and the cellular autophagic activity was determined by Western blotting of LC3 and p62. Caspase 3 fragmentation and Akt activation was also determined by Western blotting., Results: VCR induced cell cycle arrest and apoptosis in HXO-Rb44 cells, but only inhibited autophagy at relatively high doses. Both CQ and 3-MA were synergistic with VCR to inhibit the growth of retinoblastoma cells and the combinational use significantly reduced the dosage of each drug. The lowest effective dose of CQ and 3-MA was most efficient to add on VCR; however, such dose was not sufficient to suppress autophagy in these cells. CQ could directly induce caspase activation, while 3-MA significantly inhibited Akt phosphorylation., Conclusions: CQ and 3-MA were synergistic with VCR to inhibit retinoblastoma cells. Our result suggested a novel strategy to combine CQ or 3-MA with VCR to reduce the side effects of each drug. However, lack of change in the autophagic activity when using the two drugs at lower doses suggests multiple mechanisms of action of the same drug at different doses. At higher doses, the drugs could inhibit autophagy, while at lower doses, they suppress tumor growth via autophagy-independent mechanisms.

Autophagy is a dynamic process accomplished by the generation and maturation of autophagosomes. Isolation of autophagosomes and subsequent compositional analysis can provide information about their biogenesis mechanism. In this article, HEK293 cells expressing GFP-LC3 were treated by calcium phosphate precipitates (CPP) to induce autophagy. The autophaogomes induced by CPP were tubular and vesicular structures, extensively formed in the cytosol. After all membranes in the cell lysate were fractionated by differential centrifugation, autophagosomes from light and heavy membranes were isolated by immuno-precipitation, using antibodies against GFP-LC3 and Atg5. We found that GFP-LC3 and Atg5 positive autophagosomes represented distinctive subpopulations. Judged from the molecular markers associated, including organelle markers and Atg proteins, GFP-LC3 positive autophagosomes were overall at the later biogenetic stage. Furthermore, both GFP-LC3 and Atg5 positive autophagosomes from light membranes were less mature than those from heavy membranes. We have established a method to isolate subpopulations of autophagsomes for further characterization.