Abstract:Although chronic infection with various pathogens including viruses directly contributes to only approximately 25% of cancers worldwide, chronic inflammation is closely linked to the development, progression and prognosis of most human cancers. In this article the author bring forth a hypothesis termed as "Cancer Evolution-Development" (Cancer Evo-Dev), which is based on our series of studies on the molecular mechanisms of HBV infection-induced hepatocarcinogenesis, gastrointestinal and urological cancers, and world wide advances in this field. The core theory of this hypothesis is: the imbalance or dysfunction caused by the interactions of genetic predispositions and environmental exposures such as viral infection is responsible for the maintenance of chronic non-resolving inflammation. Then non-resolving inflammation promotes cancer occurrence and progression and persists throughout the cancer evolution, which is characterized by a process of "mutation-selection-adaptation". Under the microenvironment of non-resolving inflammation, pro-inflammatory factors promote mutations in viral or host genomes by trans-activating cytidine deaminases and their analogues or by inducing oxidative stress. The majority of cells acquired somatic mutations and mutated viruses are eliminated in survival competition; only a small percentage of the mutated cells are selected and function as cancer-initiating cells; these mutated cells have altered survival signaling pathways and undergo epithelial-to-mesenchymal transition via epigenetic modification by proinflammatory molecules in an inflammatory microenvironment. The selected cells exhibit the characteristics of "stemness" such as overcoming senescence, robbing nutrition, and proliferating immortally, thus promotes carcinogenesis and invasion. Cancers generally possess the properties of "backward evolution" and "retro-differentiation", suggesting the indispensability of stem-like signaling pathways in cancer Evo-Dev. This hypothesis of Cancer Evo-Dev is expected to be not only testable in understanding the inherent mechanisms by which inflammation promotes the development of cancers, but also instructive for the prophylaxis and control of cancers in the model of predictive, preventive, personalized, and participatory (P4) medicine.

Abstract:The development and progression of colorectal cancer (CRC) is a process that accumulates the driver somatic mutations elicited by chronic inflammation. Epigenetic modifications and genetic mutations play key roles in the whole evolutionary process of chronic inflammation-induced CRC. Adenoma gradually progresses into adenocarcinoma via accumulating genetic mutations stimulated by cancer promoting stimulations. The next generation sequencing technology provides an effective way to identify the "driver" mutations and fusion genes in the carcinogenesis, providing molecular evidences for cancer evolution. The most significant genetic changes during malignant transformation from adenoma to adenocarcinoma are the significant increases in microsatellite instability and chromosome instability. The main purpose of investigating the evolutionary process of CRC, especially somatic mutations, is to identify the related signaling pathways, which are the key steps to explore early effective intervention strategies and targeted therapies for CRC.

Abstract:Hepatitis B virus (HBV) infection has always been one of the most important public health issues in mainland China, causing a huge disease burden. It often takes decades for the chronic process of malignant transformation from HBV infection to different stages of liver diseases. Mutations associated with virus survival are eventually selected by the chronic infection process and under the immune pressure of host. These selected HBV mutations further promote the malignant transformation of liver diseases. A large amount of somatic mutations are produced in the HBV-related chronic inflammatory micro-environment, and those survival-related mutations will then be selected. The selected HBV mutations and host somatic mutations work together to promote the malignant transformation, which can be termed as an evolutionary process of "mutation-selection-adaptation". In addition, genetic variations of individual hosts also play an important role in HBV related disease progression. For example, single-nucleotide polymorphisms of STAT pathway and HLA can interact with important HBV mutations and therefore affect HBV-related disease progression.

Abstract:Hepatocellular carcinoma is the most commonly-seen primary liver cancer in China, with its etiology still not fully understood. Research has shown that many signaling pathways are involved in the development and progression of liver cancer, including vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, insulin-like growth factors receptor, and so on. The abnormality of these signaling pathways finally leads to cell proliferation, angiogenesis, invasion and metastasis, and apoptosis tolerance. The current treatment of liver cancer mainly includes drugs, surgery, radiation therapy and immune therapy, but there is still an urgent needs for more effective treatment with less adverse effect. It is hoped that with the progression in the signal pathways of hepatic cancer, anti-tumor treatments with these signal pathways as the targets will cast new lights for liver cancer treatment.

Abstract:Objective To investigate the role of Annexin A7(ANXA7) in the development of HCC by analyzing ANXA7 expression in hepatocarcinogenesis and identifying its potential interaction molecule. Methods NXA7 mRNA expression was analyzed by real-time PCR in 48 HCC tissues and tumor adjacent tissues, and different hepatic cancer tissues and cell lines. To analyze the effect of ANXA7 on hepatoma proliferation, ANXA7 was overexpressed or inhibited by specific siRNA in hepatic cancer cells. Co-immunopricipitation (co-IP) method was used to detect the specific binding protein of ANXA7 in HCC cells. The key sites of protein interaction were analyzed by point mutation. Western blotting analysis was used to study the effect of ANXA7 on IGFBP2 activated ERK1/2 phosphorylation. Results The expression of ANXA7 was down-regulated in both hepatoma tissue samples and hepatoma cell lines. Insulin-like growth factors binding protein 2 (IGFBP2) could specifically bind with ANXA7 through the key RGD site. Up-regulated expression of ANXA7 could inhibit the proliferation of tumor cells (P<0.05) and decrease the phosphorylation of ERK1/2. Accordingly, down-regulated expression of ANXA7 could enhance the proliferation of tumor cells (P<0.01) and increase phosphorylation of ERK1/2 in HCC cells. Conclusion ANXA7 may serve as a potential tumor suppressive molecule, participating in the regulation of IGFBP2-activated ERK1/2 phosphorylation and affecting the proliferation of hepatoma cells.

Abstract:Objective To screen for molecular markers associated with the prognosis of extrahepatic cholangiocarcinoma (EHCC) after radical excision by observing the difference of bile metabolomics during perioperative period. Methods Twenty-seven patients with EHCC, including 19 with hilar cholangiocarcinoma and 8 with distal cholangiocarcinoma, were included in this study. Their bile samples were collected before and 1, 7 days after operation. Metabonomics method using gas chromatography-mass spectrometry(GC-MS)was employed to analyze the different metabolites at different time points. Correlation analysis was performed between the common different metabolites and the patient prognosis. Results Five kinds of metabolites in the bile were notably increased 1 day after operation compared with that before operation, no metabolites were decreased. Three kinds of metabolites were notably increased and another 3 were notably decreased 7 days after operation compared with before operation. Among the above two groups of different metabolites, there were 2 common metabolites: benzoic acid and methylmalonic acid. The one year recurrence rate of patients with benzoic acid increased ≥2 times at 7 days after operation was significantly lower than that increased <2 times (P=0.04). No significant correlation was found between the change of methylmalonic acid and the early relapse in 1 year after operation. Moreover, bivariate correlation showed that the changes of benzoic acid metaboilic level in bile were not significantly correlated with the serum CA19-9, age of patients, or TNM stage (P>0.05). Conclusion The change of benzoic acid metaboilic level in bile during perioperative period can help to predict the early relapse in extrahepatic cholangiocarcinoma patients after curative resection.

Abstract:Objective To observe the outcome of cryopreserved platelet-rich plasma(PRP) in repairing rabbit calvarial bone defect. Methods Totally 15 male New Zealand rabbits, weighing 2.5 kg, were used in this study. Three defect holes were made along the calvarial midline in each rabbit; the upper defect holes were repaired with hydroxyapatite/tricalcium phosphate (HAP/TCP) compounded －80℃ cryopreserved PRP gel (experimental hole), the middle defect hole with HAP/TCP compounded physiological saline (blank hole), and the lower defect hole with HAP/TCP compounded fresh PRP gel (control hole). Five rabbits were sacrificed at 4, 8, and 12 weeks after operation, respectively. Gross observation, X-ray examination, histological observation, and CT scan were performed for the harvested samples, so as to observe whether －80℃ cryopreserved PRP gel could promote the defect repair. Results It was found that the osteogenesis of the defects in the experimental holes and the control holes were better than that in the blank holes at 4 weeks and 8 weeks after operation, with the CT values in the experimental hole, control hole and blank hole being (376.8±50.41), (414±71.41), and (94.42±37.02) at 4 weeks after operation and (750.46±91.26), (682.22±111.53), and (444.04±47.12) at 8 weeks after operation, respectively, showing significant differences(P<0.01); but there was no significant difference between the experimental holes and the control holes at both 4 weeks and 8 weeks after operation(P>0.05). At 12 weeks after operation, no differences in the osteogenesis of the defects were noticed between the three holes(P>0.05). Conclusion Cryopreserved PRP is confirmed to have the same effect as fresh PRP in enhancing early repair of calvarial bone defects.

Abstract:Objective To establish a method for determining the recovery of rocuronium microdialysis probe by LC-MS/MS, so as to investigate the stability and reproducibility of microdialysis probe recovery during in vivo and in vitro microdialysis trials and to provide evidence for in vivo microdialysis. Methods The concentration of rocuronium in dialysate was determined by LC-MS/MS and the probe recovery was calculated.The effects of different drug concentrations (50, 200, and 500 ng/mL) and flow rates(0.5, 1.0, 2.0, 3.0, and 4.0 μL/min)on the probe recovery were determined by incremental (dialysis) and reduction (retrodialysis) methods. The in vivo probe recovery in SD rats was determined by reduction method, and its result was compared with that of the in vitro trial. Results The in vitro probe recovery decreased with the increase of flow rate within a range of 0.5-4 μL/min under the same condition. At the same flow rate, different concentrations of rocuronium had little influence on the probe recovery. Under the same condition, the in vitro recovery obtained by incremental and reduction methods were approximately equal and showed a good stability. The in vivo probe recovery obtained by reduction method was similar to the in vitro one. Conclusion Microdialysis can be used for pharmacokinetic study of rocuronium, and retrodialysis method can be used to study probe recovery of rocuronium in vivo.

Abstract:Objective To investigate the optimal b value in diffusion weighted MR imaging for diagnosis of prostate cancer at 3-T while using magnetic resonance/transrectal ultrasound (MR/TRUS) fusion-guided biopsy and system biopsy pathological findings as reference standard. Methods Forty-three consecutive patients were enrolled in this prospective study; they were suspected to have prostate cancer and underwent T₂WI and diffusion-weighted MRI with 10 b-values (0,50,100,150,200,500,800,1 000,1 500,and 2 000 s/mm²) prior to biopsy. DWI combined with T₂WI analysis was used for detecting prostate cancer. The biopsy modality was decided by the MRI results: patients had suspicious lesions took MR/TRUS fusion-guided biopsy and system biopsy and those had no suspicious lesions took system biopsy only. The signal intensity of prostate cancer lesions and normal prostate tissue on DWI of different b values were measured. Statistical analyses were performed by a Wilcoxon Signed Ranks test to compare the signal intensities between prostate cancer and normal prostate tissue. Receiver operating characteristics (ROC) were used to calculate the AUC, sensitivity, and specificity, so as to determine the optimal b value for revealing prostate cancer on DWI. Results Twenty-two of the 43 patients were diagnosed as prostate cancer, with 16 diagnosed as benign prostate hyperplasia (BPH) and 5 as prostatitis. Among the 22 prostate cancer patients b=1 500 s/mm² and b=2 000 s/mm² DWI images provided the best lesion visibility in 16/22 and in 6/22 patients, respectively. Wilcoxon Signed Ranks test showed that the signal intensities of the lesions and the normal tissues were significantly different(P<0.000 1) at all b values but when at 500 s/mm² (P=0.236). ROC curve indicated that the optimal signal intensity contrast was obtained at b=1 500 s/mm² (P<0.000 1, AUC=0.933), and the signal intensity cut-off value was 49.2, with the sensitivity and specificity being 0.909 and 0.909, respectively. Conclusion A b value of 1 500 s/mm² is optimal for 3-T DWI to visualize prostate cancer lesions, and b=500 s/mm² has the lowest diagnosis efficiency.

Abstract:Objective To establish a prediction model by multivariate logistic regression analysis for estimating the malignant probability of solitary pulmonary nodules (SPNs), and to compare our model with other models. Methods From January 2011 to November 2014, totally 252 patients with SPNs who had undergone pneumonectomies in Thoracic Surgery Department of Changhai Hospital and been confirmed with definite pathological results were included in this retrospective study. The gender, age, symptom, smoking history, history of pulmonary diseases, history of tumor, family history of tumor, the location of lesion, maximum diameter, clear border, smooth border, spiculation, lobulation, spinous protuberant sign, pleural indentation, calcification, vessel convergence sign, and lucency shadow were all reviewed. Eighty-three cases were designated as validation group (group B), and the remaining 169 cases were taken as the modeling group (group A). Six cases were excluded from group B to meet all the inclusion and exclusion criteria of the other three models, and the remaining 77 cases constituted group C. Logistic analysis identified five independent factors associated with malignant probability of SPNs from group A and a clinical prediction model was built. With the data of group B and group C, this model was verified and was compared with the other three classical models. Results The age, history of tumor, maximum diameter, calcification, and lucency shadow were the five factors identified for differentiating benign and malignant SPNs (P<0.05). When group B data was substituted into the established formula, the area under curve (AUC) of the ROC was 0.905±0.036, sensitivity was 79.3%, specificity was 84.0%, positive likelihood ratio was 4.957, negative likelihood ratio was 0.246, positive predictive value was 0.920, and negative predictive value was 0.636. When the data of group C were fed to the four formulas of Changhai, Li Yun, Mayo and VA models, the corresponding AUCs were 0.893±0.040, 0.817±0.056, 0.804±0.050, and 0.780±0.057, respectively. Conclusion The patient's age, history of tumor, maximum diameter, calcification, and lucency shadow are the independent predictors of malignant probability of SPNs. This logistic regression prediction mathematic model is of clinical application value. For patients in this study, our Changhai model seems to work better than the Li Yun, Mayo,and VA model.

Abstract:Objective To design and synthesize a series of sinomenine derivatives and to investigate their anti-inflammation activities in vitro. Methods Nine sinomenine derivatives were synthesized via demethylate of N atom, nucleophilic substitution and classical Click Reaction using sinomenine as the starting material. The target compounds were evaluated for their influence on NF-κB transcriptional activity in vitro. Results All the synthesized compounds were reported for the first time, and they were confirmed by ¹HNMR and LC-MS. Biological studies showed that all the synthetic derivatives exhibited certain inhibitory effect against NF-κB transfection in vitro, but was weaker than that of sinomenine. Conclusion Replacing N-methyl with large group or long side chain on nitrogen atom may weaken the anti-inflammatory activity of sinomenine.

Abstract:Objective To observe the effect of the UbcH10 gene silencing on inhibition effect of doxorubicin against in vivo tumor formation of drug-resistant breast cancer MCF-7/ADR cells. Methods An MCF-7/ADR-UbcH10-RNAi cell line with UbcH10 gene silenced was established. Then MCF-7/ADR-UbcH10-RNAi cells and the control cells at logarithmic phase were inoculated into nude mice to establish the subcutaneous tumor model. Doxorubicin or normal saline was administered for a consecutive of two weeks, and then one week later the tumor volumes were determined to analyze the effects of UbcH10 gene silencing on inhibition of tumor formation by doxorubicin. Meanwhile, Western blotting analysis was used to examine the protein expression of UbcH10 and BCL-2; the relationship between UbcH10 and chemosensitivity of tumor cells was analyzed. Results The MCF-7/ADR-UbcH10-RNAi cell line with UbcH10 gene silenced was successfully established with the lentiviral experimental system. The nude mice tumor models were established three weeks after subcutaneous inoculation of tumor cells. The tumor inhibitory rate was 4.16% in the doxorubicin group, which was not significantly different from the control group (P>0.05); while the tumor inhibitory rate was 41.8% in UbcH10-RNAi+doxorubicin group, which was significantly higher than that in the control group (P<0.05). The results of Western blotting analysis showed that the expression levels of UbcH10 in MCF-7/ADR group, MCF-7/ADR+doxorubicin group, and MCF-7/ADR-UbcH10-RNAi+doxorubicin group were 0.81±0.16, 0.78±0.12, and 0.18±0.04, respectively, with the latter being significantly lower than the former two (P<0.05); BCL-2 protein levels in tumors were consistent with those of UbcH10. Conclusion UbcH10 gene silencing can markedly enhance the in vivo sensitivity of drug resistant breast cancer cells to Doxorubicin.

Abstract:Parkinson disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantial nigra and the formation of intracellular Lewy body. Protein nitration due to oxidative and nitrative stress has been linked to the pathogenesis of PD. Here we described the biophysical and biochemical properties of α-synuclein and nitrated α-synuclein protein and reviewed their biological consequences; finally we discussed their roles in the mechanism and prevention/treatment of PD.

Abstract:The normal cardiac function relies on highly specialized subcellular architectures. The subcellular domains junctional membrane complexes (JMCs) are essential for excitation-contraction coupling of the myocardium. Junctophilin-2 (JPH2) has been widely recognized as the crucial structural protein involved in JMCs. Initial studies limited the role of JPH2 to anchoring junctional sarcoplasmic reticulum (SR) and transverse-tubule (T-tubule) membrane invaginations. Recently, researchers have found an expanded role of JPH2 in the development of postnatal T-tubule in mammals, progression of disease in failing hearts, hypertrophic cardiomyopathy and arrhythmias. In this review we summarized the role of JPH2 in the above physiological or pathophysiological processes and discussed the perspective in future investigation.

Abstract:Metabolic syndrome is characterized by simultaneous occurrence of central obesity, hyperglycemia, dyslipidemia and hypertension, posing a serious health problem. Exercise plays a pivotal role in preventing and treating metabolic syndrome: it can (1)reduce weight and improve the fat deposit in organs; (2) improve insulin sensitivity and glucose transporter4 level and down-regulate blood glucose by promoting muscle glucose utilization; (3) improve the vascular endothelial function, increase the secretion of nitric oxide, decrease the secretion of endothelin, and finally reduce blood pressure; and (4)decrease blood levels of triglyceride and low density lipoprotein cholesterol, and increase the level of high density lipoprotein cholesterol. This paper is to review the effect of exercise on metabolic syndrome in an all around manner.

Abstract:Objective To evaluate the safety and efficacy of using blunt-tip needle to suture the dorsal venous complex (DVC) in laparoscopic radical prostatectomy. Methods The clinical data and the operation videos of patients, who received laparoscopic and robot-assisted radical prostatectomies by a single surgeon in our hospital from Jan. 2012 to Jul. 2014, were retrospectively reviewed. The needles used to suture DVC, exposure of suture points, bleeding of DVC, and cases of mistakenly sutured catheter and positive margins at the epic were analyzed. Continence of patients was followed and analyzed 3 months after surgery. Results A total of 104 cases were enrolled in this study. DVC was sutured with traditional needles in 56 cases, and in 52 of them the junction between prostate epic and membranous urethra (so called golden eye) could be exposed. DVC was sutured with blunt-tip needles in 48 cases, and the "golden eye" could be found in 44 of them. Suturing with blunt-tip needles, compared with traditional needles, resulted in significantly less bleeding and significantly better continence recovery (P<0.05). Conclusion Dorsal venous complex can be completely sutured by using blunt-tip needle once the "golden eye" is correctly indentified, which can decease the intraoperative bleeding and maintain a clear surgical field, improving the postoperative continence recovery.

Abstract:Objective To establish an effective method for the determining hypoxanthine, xanthine, uridine and uracil in earthworm in Shanghai Pheretima and Pheretima aspergillum (E. Perrier), contributing to quality control of the medicinal material. Methods Hypoxanthine, xanthine, uridine and uracil were extracted from the earthworms with 0.9% NaCl by ultrasonic and determined by HPLC. The chromatographic conditions were: SORBAX SB-Aq column (250 mm×4.6 mm, 5 μm, Aglient Co.,Ltd), 5 mmol/L KH₂PO₄ (pH 2.9) as the mobile phase with a flow rate of 1 mL/min,the detection wavelength was 254nm, the column temperature was set at 30℃, and the injection volume was 10 μL. Hypoxanthine, xanthine, uridine and uracil were determined by HPLC at the same time. Results The linear range was 0.5-100 μg (r=0.999 9) for hypoxanthine, with the average recovery being 99.37%, RSD=1.36% (n=6). The linear range was 0.5-100 μg (r=0.993 1) for xanthine, with the average recovery being 91.57%, RSD=1.40% (n=6). The linear range was 0.5-100 μg (r=0.999 9) for uridine, with the average recovery being 95.31%, RSD=1.64% (n=6). The linear range was 0.5-100 μg (r=0.999 9) for uracil, with the average recovery being 100.21%, RSD=1.98% (n=6). Conclusion The current method is reproducible and has satisfactory recovery, and it can be used to determine hypoxanthine, xanthine, uridine and uracil in earthworm medicinal material.

Abstract:Objective To explore the value of solifenacin in managing bladder irritative symptoms after transurethral resection of bladder tumor. Methods A total of 116 patients with the diagnosis of non-muscle invasive bladder carcinoma were enrolled in the present study, and they were randomly allocated into experiment group and control group. All patients received transurethral resection of bladder cancer and immediate postoperative instillation of epirubicin. Patients in the experiment group also received solifenacin 5 mg at 6 h before surgery and once a day after surgery for 3 d, while the patients in the control group received placebo. The incidences and severity of catheter related bladder discomfort were recorded at 6, 12, 24, 48 and 72 h after surgery. Results The incidence rate of bladder irritative symptoms significantly decreased from 93.1% in the control group to 67.2% in the experiment group(P=0.001). Compared with the control group, the severity of bladder irritative symptoms in the experiment group was significantly improved at all time points (P<0.05 or P<0.01). Conclusion Solifenacin is effective for managing bladder irritative symptoms after transurethral resection of bladder tumors.

Abstract:Objective To evaluate the effects of meal replacement (Glucerna SR, Abbort) on weight loss and fat redistribution in patients with simple obesity. Methods Twenty-two simple obesity patients received dinner replacement with Glucerna for five weeks (6 spoons, about 52 g per time, 220.48 kcal [1 772 kJ]), once a day at night replacing dinner. The weight, blood pressure, BMI, lipid, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose, and insulin were all observed before and after dinner replacement. The fat distribution was detected by DEXA (dual energy X-ray absorptiometry). The study was done by before-after design in the same patients. Results The body weight (P<0.001) and BMI (P<0.001) were significantly decreased after dinner replacement in our group. Dinner replacement also led to significant decrease of total fat mass (P=0.035), fat mass percentage (P=0.033) and trunk fat mass (P=0.002), while the decreases of peripheral fat mass and arm fat/leg fat mass were not significant. Lipid profiles showed that TG was significantly decreased (P=0.028)and HDL was significantly increased (P<0.001) after dinner replacement. Dinner replacement with Glucerna also resulted in a reduced HOMA-IR, though without statistical significance (P=0.372). Conclusion Dinner replacement can greatly reduce the weight of obese patients, improving fat distribution and regulating blood lipid and glucose. Dinner replacement is tolerable and safe, and it can improve the metabolism of obese patients.

Abstract:Objective To compare the cognitive function changes of newly-recruited male soldiers after exposure to 3 700 m altitude for 3 months and 15 months. Methods Using "pretest-posttest design", we selected 22 newly-recruited male soldiers in this experiment, and 8 cognitive function variables, namely, the reaction and motion time, speed-perception, time-perception, depth-perception, operating-dexterity, memory span, short-term memory and attention span were analyzed by paired comparison for 3 months and 15 months. Results Compared with soldiers exposed for 3 months, those exposed for 15 months had significantly increased reaction time (P<0.05), significantly decreased operating-dexterity performance (P<0.05), and significantly improved memory (P<0.05). The depth-perception was more liable to have the "see close" phenomenon. Conclusion Compared to those exposed to high altitude environment for 3 months, newly-recruited male soldiers exposed for 15 months have a more apparent damage to the reaction time, depth-perception, operating-dexterity and attention.

Abstract:Objective To study the pharmacokinetics of neostigmine bromide multivesicular liposomes (NB-MVLs) and conventional neostigmine bromide (NB) injection in rats. Methods Twelve healthy rats, half male and half female, were randomly divided into two groups. One group was injected with NB-MVLs and the other with reference NB (0.15 mg/kg). RP-HPLC was used to examine neostigmine concentrations in rat plasma at different time points, and the pharmacokinetic parameters and relative bio-availability were calculated. Results Pharmacokinetic parameters of NB-MVLs and NB were as follows: AUC_0-t (35.56±4.62) mg·h·L^-1 vs (15.97±5.22) mg·h·L^-1;T_max(2.40±0.89) h vs (0.45±0.11) h; C_max (2.49±0.31) mg/L vs (4.61±0.91) mg/L; and t_1/2 (15.14± 6.81) h vs (1.79±0.27) h, respectively. AUC_0-t, AUC_0-∞ and C_max were studied by DAS 2.1.1 software for double unilateral t test and [1-2α] 90% confidence interval, and T_max was precessed by Wilcoxon nonparametric test to evaluate the bioequivalence of NB-MVLs and NB. The result showed that NB-MVLs and NB were not bioequivalent. Conclusion Neostigmine in the form of multivesicular liposomes has improved bioavailability and stable drug release; NB-MVLs and NB are not bioequivalent.

Abstract:Objective To assess disease spectrum and clinico-pathological characteristics of infective endocarditis(IE) in patients with congenital heart disease(CHD). Methods Clinical characteristics of IE patients with CHD were investigated,who were receiving surgical treatment and pathological diagnosis during 2010.01-2013.12 in Changhai hospital. The clinical datas，disease species and clinico-pathological characteristics were retrospectively analyzed. Results During these 4 years, there were 58 IE cases associated with CHD whose mean age is (28.3±7.3)years accounting for 33.7％(58/172) of all patients with IE receiving surgical treatment. The top three types of congenital heart disease were included bicuspid aortic valve accounted for 34.5% (20/58), ventricular septal defect(VSD) accounted for 20.7% (12/58) and patent ductus arteriosus(PDA) accounted for 15.5% (9/58). Other congenital heart diseases (including aortic stenosis, subaortic stenosis, aortic sinus aneurysm right ventricular fistula, mitral stenosis, mitral incompetence and pulmonary stenosis) accounted for 13.8% (8/58),while complex CHD (containing two or more abnormalities) accounted for 15.5% (9/58). Mean age of bicuspid aortic valve patient was higher than other CHD patients with infective endocarditis [(38.7 ± 11.7) years vs (26.6 ± 12.4) years, P <0.05]. Positive rate of blood culture were 42.1% (25/58),in which viridans accounted for 48.0%(12/25). Echocardiography was performed in all patients and the positive rate was 96.6%(56/58) It was common that excrescence attached multiple sites, For patients with bicuspid aortic valve, excrescence often attached aortic valve, for VSD patients, excrescence often attached tricuspid septal leaflet and VSD right ventricular surface,while for PDA patients,was aortic valve,opening of PDA or the left pulmonary artery wall eroded by shunt. Conclusion CHD is common underlying disease for IE , in which bicuspid aortic valve ranks first, VSD and PDA also occupy a high proportion. Blood culture positive rate is low, while transthoracic echocardiography(TTE) is recommended as a reliable inspection techniques. Different diseases have different parts of the vegetation involving, more common is that multiple sites are involved.