Objective:To investigate the effect of IL-35 on inflammatory response and T cell response in allergic rhinitis.Methods: 37 patients(observation group) with allergic rhinitis and 35 healthy volunteers(control group) after allergen detection of allergic rhinitisin in our hospital from Jan 2012 to Jan 2016 were selected as study subjects.The peripheral blood of observation group and control group were collected,and the serum levels of IL-35 were detected by ELISA.The animal model of allergic rhinitis in mice was established,the peripheral blood of mice was collected,and the serum level of IL-35 and IgE were detected by ELISA.The eosinophils that infiltrated in nasal mucosa were detected after tissue biopsy in mice.The mouse spleen cells were isolated and the ovalbumin antigen was added in the culture medium,IL-35 was or was not added into the culture medium,the ovalbumin specific T cell responses was detected.The cytokines IL-2,IL-4,IL-5,IL-10,IL-13,IL-17,IL-23,IL-27 and TNF-α in culture supernatant of ovalbumin specific T cells were detected by ELISA.The expression of IL-2,IL-4,IL-5,IL-10,IL-13,IL-17,IL-23,IL-27 and TNF-α in ovalbumin specific T cells were detected by Real-time PCR.The activation of JNK,Erk1/2 and p38 signal pathway in ovalbumin specific T cells were detected by Western blot.Results: The serum level of IL-35 in observation group was significantly lower than control group(P<0.05).The results showed that the number of eosinophils which infiltrated in AR mice nasal mucosa was significantly higher than normal mice(P<0.05),while the serum level of IL-35 in AR mice was significantly lower than normal mice(P<0.05).Ovalbumin specific T cell reactivity assay showed that IL-35 could significantly inhibit the T cell response.ELISA and Real-time PCR results showed that IL-35 could significantly down regulate the expression of IL-4,IL-5,IL-13,IL-17,IL-23 and TNF-α,and up regulate the expression of IL-2,IL-10 and IL-27.The Western blot results showed that IL-35 can inhibit the activation of JNK,Erk1/2 and p38 signal pathway of ovalbumin specific T in cells.Conclusion: IL-35 can regulate the expression of inflammatory cytokines in inflammatory response and inhibit T cell response,thus reducing allergic rhinitis,the mechanism may be through regulation of JNK,Erk1/2 and p38 signal pathway activation.

Objective To explore the clinical manifestations of toxic epidermal necrolysis(TEN) and its rare pulmonary complications.Methods Clinical symptoms,treatment and prognosis of 1 child with TEN caused by carbamazepine were analyzed.Radiological images were reviewed to evaluate the manifestations and the outcome of chronic pulmonary complications associated with TEN.Results The patient had high fever shortly after a dosage increment of carbamazepine.A confluent erythematous exanthema developed rapidly into painful blistering with skin erosion,denudation and involvement of conjunctive and oropharyngeal mucosa.The diagnosis of TEN was made.The mucocutaneous damage was gradually recovered with steroid plus intravenous immunoglobulin for 3 weeks.However,the patient presented with respiratory failure in the recovery phase of TEN.The computer tomography revealed pulmonary bullae and pneumothorax in the right lung.Lung parenchyma was squeezed and pulmonary bullae ruptured with pneumothorax and atelectasis,which were absorbed gradually through thoracic drainages.The patient′s lung function and pulmonary bullae were partly improved during a 7-month follow-up.Conclusions TEN is a severe form of blistering skin di-sease which is characterized by an extensive loss of epidermis and mucous membrane.Chronic pulmonary complications may occur in recovery phase of TEN.Pulmonary bullae,which might be caused by mucous damage and respiratory obstruction,is a rare complication of TEN.

To study the pharmacokinetics characteristic of loganin, ferulic acid and stilbene glucoside in rat plasma after oral administration of Bushen Tongluo formula. The plasma samples were treated by using liquid-liquid extraction technique, the concentrations were determined by HPLC-UV. Johnson spherigel C18 column (4.6 mm x 250 mm, 5 μm) was adopted and eluted with the of mobile phase of methanol-water containing 0.01% glacial acetic acid in a gradient mode, with the flow rate at 1.0 mL x min(-1), column temperature at 30 degrees C and injection volume of 10 μL. According to the findings, loganin was determined at 235 nm, ferulic acid and stilbene glucoside were determined at 320 nm, with the sample size of 10 μL. The pharmacokinetic parameters of loganin, ferulic acid and stilbene glucoside were calculated by DAS 2. 0 software as follows: C(max) was (0.369 ± 0.042), (0.387 ± 0.071), (0.233 ± 0.044) mg x L(-1); t(max) was (0.226 ± 0.022), (0.282 ± 0.031), (0.233 ± 0.044) h; t(½β) was (6.89 ± 0.20), (10.73 ± 0.11), (6.93 ± 0.09) h; AUC(0-∞) was (1.91 ± 0.36), (3.22 ± 0.52), (1.52 ± 0.33) mg x h x L(-1); AUCO(0-t) was (1.62 ± 0.33), (2.58 ± 0.43), (1.30 ± 0.30) mg x h x L(-1); CL was (20.2 ± 4.0), (1.39 ± 0.23), (31.7 ± 6.9) L x h(-1) x kg(-1), respectively. The results showed that after the oral administration with Bushen Tongluo formula, loganin, ferulic acid and stilbene glucoside showed concentration-time curves in conformity with the two compartment model, with a rapid absorption, loganin and stilbene glucoside was excreted at a moderate speed, and ferulic acid was excreted slowly (but with the highest bioavailability). Bushen Tongluo formula can main maintain plasma concentration with three administrations everyday and so is suitable to be made into common oral preparation.
Administration, Oral ; Animals ; Biological Availability ; Coumaric Acids ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Iridoids ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; administration & dosage ; blood ; pharmacokinetics

In this study, we explored the mechanism of Huganning tablet (HGNP) in the treatment of nonalcoholic fatty liver disease (NAFLD) based on network pharmacology and computer-aided drug design. Firstly, the potential ingredients and targets of HGNP were identified from TCMSP database, Swiss Target Prediction database, Chinese pharmacopoeia (2015) and literatures, and then the targets of HGNP intersected with NAFLD disease targets that obtained in GeneCards database to acquired potential targets. The bioconductor bioinformatics package of R software was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. The network of “potential ingredient-key target-pathway” was formed in Cytoscape software to study the interactions between potential ingredients of HGNP, key targets, pathways and NAFLD. Based on the results of network pharmacology, the molecular docking analysis of the key targets and potential active ingredients in HGNP tablets with top degree in the network was conducted using Discovery Studio 2020 software, followed by molecular dynamics simulations, binding free energy calculation, drug-likeness properties analysis and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties prediction. In vitro, HepG2 cells were used to establish steatosis model, and the effects of five key compounds on hepatocyte steatosis were analyzed by oil red O staining and triglyceride (TG) content determination. The results showed that 141 ingredients and 151 potential targets were obtained. A total of 2 526 items and 151 pathways were identified by GO and KEGG enrichment analysis. The molecular docking suggested that five components, isorhamnetin, salvianolic acid B, emodin, resveratrol and rhein, exhibited strong binding ability with key targets [retinoic acid receptor RXR-alpha (RXRA), tumor necrosis factor (TNF), glycogen synthase kinase-3 beta (GSK3B), serine/threonine-protein kinase 1 (AKT1)]. It was further verified that isorhamnetin and salvianolic acid B bind to key targets with good structural stability and binding affinity based on molecular dynamics simulations and binding free energy calculations. The drug-likeness properties, pharmacokinetic properties and toxicity of five key compounds were more comprehensively analyzed through drug-likeness properties analysis and ADMET properties prediction. In vitro, all five compounds, isorhamnetin, salvianolic acid B, emodin, resveratrol, and rhein, improved hepatocyte steatosis of HepG2 cells, confirming the reliability of the present study. In conclusion, based on network pharmacology, computer-aided drug design and in vitro validation, this study investigated the mechanism of HGNP for the treatment of NAFLD at multiple levels and provided a basis for its clinical application.

Objective To investigate effective treatment modalities and the related factors influencing prognosis of patients with gallbladder cancer.Methods The clinical data of 76 gallbladder carcinoma patients admitted to the Department of General Surgery,PLA Nanjing General Hospital from January 2005 to October 2015 were analyzed retrospectively.Follow-up was carried out via telephone or outpatient service until January 2016.Cox regression and Kaplan-Meier models were performed for survival analysis.Results 69 patients were treated with surgery and/or postoperative adjuvant chemotherapy.The remaining 7 patients with liver or distant metastases who did not undergo surgery received chemotherapy.24 patients died from cancer relapse,37 patients died from disease progression after giving up treatment,and 7 patients were lost to follow-up.The remaining 8 patients were still alive at the time of follow-up.The depth of cancer invasion (HR =2.736),the type surgical procedure (HR =2.207),and adjuvant chemotherapy (HR =0.603) were significant impact factors of survival for GBC patients.Adjuvant chemotherapy was a protective factor.The average survival in the chemotherapy-naive group was (10.6 ± 1.9) months,the single chemotherapy group (18.5 ± 2.8) months,and the combined chemotherapy group (26.9 ± 6.4) months.There were no significant differences among these groups.Conclusions The depth of cancer invasion,types of surgical procedure particularly radical cholecystectomy,and adjuvant chemotherapy were significant factors of survival in patients with GBC.Radical cholecystectomy combined with arterial and intravenous chemotherapy using gemcitabine and oxaliplatin showed benefits in survival in GBC patients.

Objective To study the relationships among resilience, self-awareness, personality, stress level and mental health in the warship soldiers. Methods Resilience Scale for Adults ( RSA), Eysenck Personality Questionnaire ( EPQ), Self Acceptance Questionnaire( SAQ), General Self-Efficacy Scale( GSES), Wallance Self Concept Scale (WSCS), Psychological Stress Self-evaluation Test (PSET) and Symptom Checklist (SCL-90)were used to survey 1451 warship soldiers. Results ① 2.5％ of the warship soldiers reported obvious psychological stress. Mental health of warship soldiers was worse than the norm of China population, except for obsessivecompulsive and interpersonal sensitivity factor. While the scores of other factors were significantly higher than the norm of Chinese soldiers(P＜0.01). ②The total scores of SCL-90, psychological stress and resilience, internal/external had negative correlation with self-awareness, and positive correlation with neuroticism. Compared to the SCL-90-negative group,SCL-90-positive soldiers (SCL-90 total score ＞ 160) had higher scores of nervousness and PSET and lower scores of RSA, internal/external and self-awareness (P ＜ 0.01 ). ③Regression analysis showed that stress levels, emotional stability,self-awareness and resilience were able to predict 35.1％ of mental health in warship soldiers. Mental health, emotional stability, internal/external and resilience were able to predict 33.2％of individual's stress level. Conclusion To some extent, warship soldiers have psychological stress and mental health problems. Resilience, personality, self-awareness are important factors affecting psychological stress and mental health.

Cytokines ; physiology ; Fas Ligand Protein ; Fatty Liver ; etiology ; metabolism ; Humans ; Ion Channels ; Lipid Peroxidation ; Membrane Glycoproteins ; physiology ; Membrane Transport Proteins ; Mitochondria ; metabolism ; Mitochondrial Proteins ; Proteins ; physiology ; Reactive Oxygen Species ; Uncoupling Protein 2

OBJECTIVETo evaluate the clinical outcome of accessory navicular fusion for treatment of the painful accessory navicular bone of type II in adults.

METHODSFrom June 2006 to June 2012, a total of 38 feet (in 35 adult patients) with painful accessory navicular with type I underwent an fusion operation of the primary and accessory navicular bones,including 26 males and 9 females with a mean age of (32.4±7.3) years old ranging from 18 to 44 years old. The course of disease ranged from 3 to 10 months. The perioperative complications and radiological outcomes were observed and recorded. The foot function before and after operation were assessed by the American Orthopedic Foot and Ankle Society (AOFAS) midfoot score, and the easement of the pain was evaluated by visual analog score (VAS).

RESULTSTwo patients had transient superficial inflammation of the incision, no obvious perioperative complications occurred. All patients were follow-up for (53.5±14.7) months (12 to 84 months). Bone union was confirmed on plain radiography in 32 cases (35 feet). The mean time from the operation to union was (13.7±2.3) weeks (9 to 18 weeks). Postoperative pain VAS score was improved obviosly than preoperative (V=12.14,P< 0.01). The talar-to-first metatarsal angle [(9.4±3.5)° vs (8.3±2.7)°, t=0.736, P>0.05)], calcaneal tilt angle [(17.7±2.2)° vs (18.9±3.4)°, t=0.794, P>0.05],talonavicular uncoverage angle [(14.3±3.4)° vs(12.5?4.6)°,t=0.947, P>0.05) ],and height of the first tarsometatarsal joint [(14.8±3.1) mm vs (15.9±2.8) mm,t=0.814,P>0.05)] before and after operations had no statistic difference. The AOFAS midfoot score was improced from preoperative 45.6±5.3 to postoperative 82.5±7.4 (t=3.214,P< 0.01).

CONCLUSIONFor the painful accessory navicular bone of type II in adults, if the patient has a large navicular bone and not complicated with rigid flatfoot, once the conservative treatment fails, fusion of the primary and accessory naviculars may be a successful intervention. Overall, the procedure provides reliable pain relief, definite foot function improvement, and good patient satisfaction.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Foot Diseases ; physiopathology ; surgery ; Humans ; Male ; Tarsal Bones ; abnormalities ; physiopathology ; surgery ; Treatment Outcome ; Young Adult

Objective To investigate a new method of improving design of the skin flap pedicled with descending hranch of lateral femoral circumflex artery,in order to increase the accuracy of preoperative Doppler location.Methods Six fresh cadavers underwent a whole body,intra-arterial injection of a lead ox- ide and gelatine preparation.Observe the perforators of anterolateral thigh by dissection,measured their diam- eter;course,branches and location for there were showed up by angiography and photography.A specific pro- gram,3D-doctor,was used for the detection of the regions of interest in angisome and its 3D-reconstructive.In addition to the average area supplied by a single perforator within that territory was calculated from digital an- giograms using Scion Image.Results There were 16 perforators that the diameter≥0.5 ram,20%were septocutaneous,80%were musculocutaneous.Their average external diameter was 0.8 ram.The average ped- icle length from the deep fascia was(3.15?1.43)ram;the perforators from descending branch of lateral cir- cumflex femoral artery walk length average about 2.63 cm in superficial fascia.The area of each perforator supplied blood was average 45.61 cm~2.Conclusion Modified lead oxid-gelatine technique provides high quality angiograms for the study of cutaneous artery and perforator falp.Based on our data,the maximum di- mension of the anterolateral thigh perforator flap can be 30 cm?20 cm in with only a single dominant perfora- tor.The perforator flaps deviced by perforators from the anterolateral thigh are transplanted to the lower limbs and the other part of the body.

BACKGROUND: Induced pluripotent stem cells (iPSCs) are a special type of cells with self-renewal and multi-differentiation potential, which can differentiate into intestinal organoids under certain conditions. OBJECTIVE: To explore whether iPSCs can differentiate into intestinal organoids under specific conditions in vitro.METHODS: iPSCs from B6J mice were recovered and cultured for 3 days until clone units covered about 80％ of the culture dish, and then the cells were cultured in the medium containing Activin A for 3 days until the deterministic endoderm formed. Further, the culture medium was replaced by the medium with fibroblast growth factor 4 and Wnt3A for 4 days to differentiate into the spheroids with CDX2+. After that, spheroids were collected and mixed with Matrigel,and then the mixture was dropped into the 4-well plate and cultured with Rspondin1, Noggin, epidermal growth factor, B27 and other growth factors to differentiate into intestinal organoids. Cell morphology was observed, FoxA2 and Sox17 expresson in the deterministic endoderm was detected, and CDX2, Sox9, CGA, MMP7 were measured.RESULTS AND CONCLUSION: iPSCs were cultured with Activin A for 3 days with higher cell fusion, initial differentiation and FoxA2/Sox17 expression (P < 0.05) than those of non-induced iPSCs. Spheroids began to appear at the 3rd day after culture with fibroblast growth factor 4 and WNT3A, and formed a lot at the 4th day. And CDX2 expression in spheroids was significantly increased compared with that in the deterministic endoderm (P < 0.05). Organoids gradually formed after 3 days culture, which contained all cell types of intestinal organoids, and expressions of specific markers, Sox9, CGA, MMP7, were significantly higher than those in spheroids (P < 0.05). To conclude, iPSCs can be induced to differentiate into intestinal organoids in three-dimensional niche in vitro.