Objective:To study the protective effects of sea buckthorn polysaccharide extracts on lipopolysaccharide( LPS)/D-galactosa mine ( D-GalN )-induced liver injury in mice and investigate the regulation on hepatic TLR4 and SOCS3 expression.Methods:C57BL/6 male mice were randomly divided into six groups:control group,model group,dexamethasone positive control group, low, medium and high dose group of sea buckthorn polysaccharide.Mice in the sea buckthorn polysaccharides low, medium and high dose group were gavaged with 50, 100 and 200 mg/kg sea buckthorn polysaccharide extracts for 14 days respectively.Acute liver injury model were established by intraperitoneal injection of LPS(10 μg/kg) and D-GalN (700 mg/kg).The mice in the dexamethasone positive control group were intraperitoneally injected with dexamethasone (10 mg/kg) before model estab-lishment.Serum and liver samples were collected after model establishment for 4 h .Serum levels of ALT and AST were detected.Histological changes of liver tissue were observed by HE staining.Hepatic expression of TLR4 and SOCS3 was detected by Western blot.Results:Sea buckthorn polysaccharide significantly inhibited LPS/D-GalN-induced elevation in serum levels of ALT and AST.It also alleviated liver cell injury and inflammatory infiltration.Western blot results showed that sea buckthorn polysaccharide inhibited LPS/D-GalN-induced TLR4 expression.SOCS3 expression was not dramatically influenced by sea buckthorn polysaccharide supplementation.Conclusion:Sea buckthorn polysaccharide protects against LPS/D-GalN-induced liver injury.This protective effects may be achieved by inhibiting the expression of TLR4 but not associated with modulation on SOCS3 expression.

English for science and technology (EST) is the language medium for academic communication among scientists and technologists. The expression of EST is characterized by concise-ness, correctness, objectiveness and understandability. The EST course is regarded as a key process for the undergraduate students to reinforce the English foundation and improve the capacity of English application after their College English study. In this paper, the authors introduced an interest-motivated, output-dominated, snowballing and interactive teaching strategy, according to the accumulated experi-ence of EST teaching in the past few years coupled with the unique medicine-engineering combined characteristics for the major of biomedical engineering.

ObjectiveTo explore the surgical techniques and clinical experiences in treating thoracoabdominal aorta dissecting aneurysm following Sun's procedure.MethodsFrom June 2009 to May 2011,thoracoabdominal aorta replacement was performed in thirteen patients with thoracoabdominal aorta dissecting aneurysm following Sun's procedure in Beijing Anzhen Hospital.Among which,eleven were male,and two were female with a mean age 39.3 years (28 -58 years).All cases were Stanford A aortic dissection,and were underwent Sun's Procedure.The pathogeny of the dissection,ten were Marfan's syndrome,and three were hypertension.Thoracoabdominal aorta dissecting aneurysms were all Crawford type Ⅱ,with the diameter( 5.78 ± 1.00 )cm (4.0 -8.0 cm).All the procedures were performed through combined thoracoabdominal incision via the retroperitoneal approach.And thoracoabdominal aorta was replaced by a tetrafurcate graft with short-time interval circulatory arrest.24 - 30 mm tetrafurcate grafts were selected in all patients.The main graft of the tetrafurcate graft was anastomosed to the elephant truck stent graft.Visceral arteries were joined into a patch and were anastomosed to the other end of the main graft.T6 to T12 intercostal arteries were reconstructed by an 8 mm sidearm.Another 8 mm sidearm was anastomosed to the left renal artery.Both 10 mm sidearms were anastomosed to iliac arteries.Among which,seven were underwent by profound hypothermia with circulatory arrest,and six were underwent off pump with normal temperature.ResultsNo early death.Twelve patients were cured and discharged from hospital.Seven patients were underwent profound hypothermia with circulatory arrest.Among which,one patient had paraplegia,sepsis,pseudomembranous colitis,respiratory failure,and died on 102-day after operation.Another one patient had neurological dysfunction and was cured after six-day's dehydrated treatment.The UFCT showed that the tetrafurcate graft was unobstructed,no distortion,no pseudoaneurysms in all patients.The branch to intercostal arteries was obstructed in three cases,but there were no spinal cord ischemia complications.The mean duration of follow-up was (9.6 ±2.1 ) months (range,1 -24 months),with a follow-up rate of 100％.All the tetrafurcate graft were very well,no obstruction,no distortion and no pseudoaneurysms.There were no cerebral,spiral cord and abdominal viscera ischemia complications in all patients.ConclusionThoracoabdominal aorta replacement after Sun's procedure is simple,and it is helpful to reduce complications.Following Sun's procedure,using tetrafurcate graft with short-time interval circulatory arrest and off pump technique in thoracoabdominal aorta replacement is simple,and it is helpful to reduce complications.

In order to investigate the application of proton magnetic resonance spectroscopy (1H-MRS) and computerized tomography (CT) in the quantitative diagnosis of nonalcoholic fatty liver disease (NAFLD) and evaluation of therapeutic effects, 22 patients with NAFLD were selected according to the Chinese Medical Association's (CMA) standard of the NAFLD in comparison with 20 healthy volunteers (as control group). Blood samples for biochemistry were collected. The severity of hepatosteatosis was evaluated by 1H-MRS scan and CT scan of liver. The intrahepatic content of lipid (IHCL) and CT value ratio of liver to spleen were calculated. The patients in NAFLD group were treated with Ganzhixiao Capsule for 8 weeks. The changes in IHCL and CT value ratio of liver to spleen were observed before and after treatment. In NAFLD group serum ALT, TG, IHCL calculated by 1HMRS were increased and CT value ratio of liver to spleen decreased significantly as compared with control group. After treatment for 8 weeks serum ALT, TG, IHCL were decreased significantly, while CT value ratio of liver to spleen increased significantly in NAFLD group. It was suggested that IHCL could be measured precisely by 1HMRS. NAFLD was treated effectively by Ganzhixiao capsule.

Objective:To establish a method for determining the concentration of gatifloxacin in rabbit ocular tissue and compare the ocular pharmacokinetics of 0.3% gatifloxacin eye gel after a single and multiple topical instillations in rabbits.Methods:Ninety-four healthy New Zealand rabbits were selected.Ten rabbits were randomly selected without any treatment for blank tissue collection, and the remaining 84 rabbits were randomly divided into a single-dose group (36 rabbits) and a multiple-dose group (48 rabbits) equally between males and females using a random number table.The left eye was taken as the experimental eye.The single-dose group was given one drop of 0.3% gatifloxacin eye gel into the left eyes, and the rabbits were divided evenly into six subgroups.In each subgroup, tear specimens and blood specimens were collected at 0.5, 1, 3, 5, 7, 10 hours after gel application, then cardiac blood samples were taken, after which animals were sacrificed immediately to collect ocular tissue including aqueous humor, conjunctiva, cornea, sclera, iris-ciliary body, lens, vitreous body, retina, and choroid.The multiple-dose group was given 1 drop of gatifloxacin ophthalmic gel in the left eye three times a day.At 0.5 hour after the first administration days 4 and 6, and 0.5, 1, 3, 5, 7, and 10 hours after the first administration on day 7, the cardiac blood sampling and ocular tissue collection were performed.The methanol precipitation protein method was used to pretreat samples, and the concentration of gatifloxacin in rabbit plasma and eye tissue was measured and calculated by high-performance liquid chromatography-tandem mass spectrometry method to obtain pharmacokinetic-related parameters such as peak concentration (C max), peak time (T max), and area under curve (AUC).The mobile phase was a methanol-0.1% acetic acid aqueous solution (volume ratio=70∶30), and a positive ion multiple reaction detection mode was used.Ciprofloxacin was used as the internal standard, the selectivity, standard curve and lower limit of quantification, accuracy and precision, extraction recovery rate, matrix effect, and stability of the method were validated in accordance with the 9012 Guidelines for Validation of Quantitative Analysis Methods for Biological Samples in Chinese Pharmacopoeia ( 2020 edition).Combined with the minimum inhibitory concentration (MIC 90) of gatifloxacin on common ocular infectious bacteria, C max/MIC 90 and AUC/MIC 90 were calculated.The study protocol was reviewed and approved by the Animal Ethics Committee of Shenyang Xingqi Pharmaceutical Co., Ltd.(No.XQ-2016-011). Results:Gatifloxacin has a good linear relationship in various eye tissues and plasma.The between-run precision in corneal tissue is within the range of -1.5%-6.0%, and the daytime precision was not greater than 15%.The extraction recovery rate in corneal tissue ranged from 92.0% to 94.8%, and the precision of the matrix effect at low, medium, and high concentrations calculated by internal standard normalization was not greater than 3.3%.After a single topical instillation, gatifloxacin reached a high concentration in anterior and posterior segment ocular tissues and its distribution ranked in order from the highest to the lowest by AUC 0-t as follows, tears, cornea, conjunctiva, iris-ciliary body, sclera, aqueous humor, choroid, retina, lens and vitreous body, with the C max of 94.90 μg/g, 7.34 μg/g, 3.65 μg/g, 1.81 μg/g, 1.75 μg/g, 1.31 μg/ml, 0.86 μg/g, 0.53 μg/g, 0.13 μg/g and 0.07 μg/ml, respectively.T max was 1 hour in all ocular tissues except in the lens, choroid, and vitreous body fluid, where T max was 0.5 hour.There was no significant difference among the concentrations of gatifloxacin in ocular tissues at 0.5 hour on days 4, 6 and 7 after multiple dosing ( P>0.05), and the AUC 0-t in the cornea, conjunctiva, and sclera was approximately 2.04, 2.12, and 2.32 times that of the single dosing.The concentration of gatifloxacin released into the systemic circulation after single and multiple dosing was less than 25.00 ng/ml.For both Staphylococcus aureus and Staphylococcus epidermidis, pharmacokinetic/pharmacodynamics in the conjunctiva, cornea, sclera, iris-ciliary body, aqueous humor, and choroid were satisfied with C max/MIC 90≥10 and AUC/MIC 90≥30 after continuous administration of gatifloxacin ophthalmic gel. Conclusions:A rapid and sensitive method for measuring gatifloxacin concentration in ocular tissues is successfully constructed.Gatifloxacin ophthalmic gel administered three times a day for three days can achieve stable concentrations in ocular tissues, and the concentration of gatifloxacin in ocular tissues is increased compared with a single dose.Effective treatment of common bacterial infections of the conjunctiva, cornea, sclera, and iris-ciliary body can be achieved with topical application of gatifloxacin ophthalmic gel.

OBJECTIVETo investigate the different expressions of ER and ER gene status between primary and relapsed/metastatic lesions and their clinical significance.

METHODSER and ER gene status of primary and relapse/metastatic breast cancer masked in 70 metastatic breast cancer patients were assessed by determination of methylation status by immunohistochemistry (IHC) and methylation specific polymerase chain reaction (MSP), respectively.

RESULTSPositive rate of ER in the primary breast cancers was 64.3%, and in the relapse/metastatic lesions was 41.4% (P < 0.05). There were six patients whose positive ER status was changed to negative, among them the ER gene status was changed from demethylation to hypermethylation in four cases. Another four patients with negative ER status changed to positive, and their ER gene hypermethylation changed to ER demethylation status.

CONCLUSIONSThe discordance of ER expression status in primary and relapse/metastatic lesions of breast cancer might be related to DNA methylation status.

Adult ; Aged ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Breast Neoplasms, Male ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; genetics ; metabolism ; pathology ; secondary ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Liver Neoplasms ; genetics ; metabolism ; secondary ; Lung Neoplasms ; genetics ; metabolism ; secondary ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, Estrogen ; genetics ; metabolism

OBJECTIVETo explore efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) regimen by dose attenuation in locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer(MPC).

METHODSBetween April 2014 and October 2015, 35 patients with LAPC (n=18) or MPC (n=17) were treated with mFOLFIRINOX regimen (irinotecan 135 mg/m(2), oxaliplatin 68 mg/m(2), 5-FU 2 400 mg/m(2), no bolus of 5-FU, leucovorin 400 mg/m(2)) in the Second Affiliated Hospital of Zhejiang University School of Medicine. The primary end point was progression free survival. The second end points were overall survival, objective response rate, adverse effects, surgical resection rate for LAPC.

RESULTSAmong 35 patients, 6 patients (17.1%) who dropped out and received less than 2 cycles were excluded for response analysis. Among the other 29 patients, 9 patients had grade 3 or 4 adverse effects. No patients ceased treatment due to adverse effects. The 29 patients received 5 (2-13) cycles were evaluated by efficacy and found partial remission in 16 cases, stable disease in 10 cases, progression disease in 3 cases. Response rate was 55.2%. Nine patients with LAPC accomplished surgery after neoadjuvant treatment without perioperative complication and death, and 6 patients accepted R0 resection.

CONCLUSIONSThe mFOLFIRINOX regimen used in the study is well-tolerated in Chinese population with high treatment efficacy on patients with LAPC and MPC. Further investigation of efficacy and adverse effects on more advanced pancreatic cancer patients is necessary.

Antineoplastic Combined Chemotherapy Protocols ; Camptothecin ; administration & dosage ; analogs & derivatives ; Disease Progression ; Disease-Free Survival ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Neoadjuvant Therapy ; Organoplatinum Compounds ; administration & dosage ; Pancreatic Neoplasms ; drug therapy ; Tertiary Care Centers ; Treatment Outcome

Objective:To evaluate the effect of stellate ganglion block on nighttime sleep quality in the patients with primary sleep disorders.Methods:Sixty patients of both sexes with primary sleep disorders, of American Society of Anesthesiology physical status Ⅰ or Ⅱ, aged 18-64 yr, weighing 40-75 kg, were randomized to 2 groups ( n=30 each): control group (group C) and stellate ganglion block group (group S). In group S, 0.2% ropivacaine 5 ml was injected into the surface of the right longus colli muscle where the the stellate ganglion was located under ultrasound guidance once a day for 7 consecutive days starting from 1 h before bedtime.While the equal volume of normal saline was given instead in group C. Patients′ Subjective Sleep Quality was assessed using the Pittsburgh Sleep Quality Index Questionnaire before treatment (T 0) and 1-7 days after treatment.The objective sleep quality was evaluated with polysomnography.A bispectral index(BIS)monitor and a cerebral and regional blood oxygen monitoring system were used to monitor the BIS value and regional cerebral oxygen saturation (rSO 2) during sleep, which were recorded once every 30 min, and the 7-day average was calculated.The patients′ daytime advanced cognitive function was assessed for 3 consecutive days after the end of treatment (T 8-10), including the Continuous Attention Test and the Behavioral Test for Performing Defect Syndrome, and the 3-day average value was calculated.Venous blood samples were collected at T 0 and T 8 to measure the plasma noradrenaline, cortisol, and serotonin concentrations by high-performance liquid chromatography. Results:Compared with group C, the individual and total scores of Pittsburgh Sleep Quality Index were significantly decreased, the sleep latency, awakening time and fast wave sleep latency were shortened, the number of awakening was increased, the total sleep time was prolonged, the sleep efficiency and proportion of fast wave sleep were increased, S 1-S 2 ratio in slow-wave sleep was decreased, S 3-S 4 ratio was increased, BIS value was decreased, rSO 2 was increased, each parameter of Continuous Attention Test was decreased and each parameter of Behavioral Test for Performing Defect Syndrome was increased after treatment, and plasma noradrenaline level was decreased at T 8 in group S ( P<0.05). Conclusion:Stellate ganglion block can improve nighttime sleep quality in patients with primary sleep disorders.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of dupilumab in the treatment of severe asthma with rapid health technology assessment （HTA）， and to provide evidence-based evidence for clinical treatment. METHODS Retrieved from PubMed，Cochrane Library，CNKI，Wanfang， VIP database， and other related websites of HTA. HTA reports， systematic review/meta-analysis， and economic studies of dupilumab in the treatment of severe asthma were collected. Researchers independently identified literature， extracted data， and assessed the quality of included studies. Qualitative description was performed. RESULTS A total of 15 pieces of literature were included， involving 9 systematic reviews/meta-analyses and 6 economic studies. In terms of effectiveness， dupilumab was significantly better than placebo. Compared with other biological drugs， in the patients with severe asthma aged 12 years and above， for those with eosinophil （EOS） ≥300 cells/μL， dupilumab ranked first in improving forced expiratory volume in one second （FEV1）， outperforming tezepelumab， benralizumab， and mepolizumab. It ranked second in reducing acute exacerbations， surpassed only by tezepelumab， while its effect on improving asthma control questionnaire score was relatively lower， being better only than benralizumab. For those with 150 cells/μL ≤EOS＜300 cells/μL， dupilumab was superior to mepolizumab in reducing asthma exacerbation， while the effect on FEV1 was weaker than benralizumab and mepolizumab. In terms of safety， there was no significant difference in the incidence of adverse events and serious adverse events between dupilumab and placebo or other biological drugs， while the incidence of injection site reactions of dupilumab was significantly higher than placebo. In terms of cost-effectiveness， the research results of different countries were not consistent， and there was a lack of research data from China. CONCLUSIONS Dupilumab is an effective and safe choice in the treatment of severe asthma， and its cost-effectiveness requires further research based on China’s medical environment to be determined.