Gastrointestinal tumors are the major disease that threaten human health.According to statistics,more than 700 000 people died every year because of gastric cancer,1/10 of all cancer mortality.Colorectal cancer incidence of malignant tumors,which ranked third,ranked fourth in cancer deaths.At now the treatment of gastrointestinal tunors mostly are operation,radiotherapy and chemnotherapy,but to spread of tumors,doctors still haven' t more better method.Nanoparticles have properties in the diagnosis and treatment of cancer,including their size-dependent properties,stability in solvent,ideal size for delivery within the body,and tunable surface chemistry for targeted delivery.Here,the author do an overview of nanoparticles in gastrointestinal tumors ablation.

Objective To establish a method for determining the dissolution oftorasemide sustained-release tablet in vitro and study the methodology of the determination.The consistency of the in vitro release behavior between self-prepared torasemide sustained-release tablet and original preparation were evaluated by constructed method.Methods HPLC method was applied to detect the cumulative release percentage of self-prepared torasemide sustained-release tablet and original preparation in five kinds of release media (water,0.1 mol/L hydrochloric acid solution,pH 4.5 acetate buffer,pH 6.8 phosphate buffer,and 0.1 mol/L hydrochloric acid solution turn to pH 6.8 phosphate buffer).Similarity factor (f2) was used to evaluate the similarity of release curves.Results There was a good linear relationship between the quality concentration of torasemide and peak area in the range of 1.0-12.0 μg/mL (r =0.9995).Results of precision and stability tests were good,and the RSDs for probational liquid were all lower than 2.0％.The average recovery of accuracy test was 100.04％,and RSD was 0.54％ (n =12).The homogeneity of within group of self-prepared preparation met the technical requirement,RSDs of each sampling points in six Dissolution Vessels were lower than 10.0％.The f2 factors of self-prepared torasemide sustained-release tablet and original preparation were 72,60,77,66,and 60 in five kinds of release media.Conclusion The method in the paper is suitable for the release test of torasemide,meanwhile,the self-prepared tablet shows consistent in vitro release behavior with that of the original preparation.

Objective For bioequivalence test of the consistency evaluation of generic drug products,providing a reference of varieties of biowaiver.Methods Based on Human bioequivalence test waiver guidelines (draft),on condition that first drug of the consistency evaluation,to introduce and conclude briefly the standards of biowaiver and varieties of biowaiver in FDA,WHO and EMA.Results Contrast to FDA,there are 59 varieties applied for the waiver and 19 varieties not applied for the waiver in the 289 varietie;compared to WHO,10 drugs are exempted and 1 grug is exempted in EMA.Conclusion At present,the specific list of drugs are not published of biowaiver in our country,the pharmaceutical companies should compare and consult revelant standards and specific drugs in China and abroad,to speed up the progress of the consistency evaluation.

Tumor invasion and metastasis are regarded as main reasons for the failure of therpy and the reason of patients death.The mechnism of tumor metastasis is still uncertain.The pre-metastatic niche hypothesis provides us with new ideas to discover the mechnism.Numerous materials are involved in the formation of the pre-metastatic niche according to this hypothesis,including bone marrow-derived cells,microvesicles,exosomes,CD44,and so on.A further research on this hypothesis helps to deeply understand the nature of metastasis and leads clinical doctors to explore novel targets for clinical diagnoses and therapies.

Objective To compare remifentanil?propofol target?controlled infusion ( TCI ) with sufentanil?propofol TCI for sedation and analgesia in the patients undergoing local anesthesia. Methods Sixty patients, aged 17?54 yr, with body mass index <30 kg∕m2, scheduled for elective plastic surgery underlocal anesthesia, were equally and randomly divided into remifentanil group (group R) and sufentanil group(group S) by using a random number table. Remifentanil (the initial target plasma concentration 1?? 0ng∕ml) and propofol (the initial target plasma concentration 1?? 0 μg∕ml) were given by TCI in group R.Sufentanil (the initial target plasma concentration 0?? 10 ng∕ml) and propofol (the initial target plasma con?centration 1?? 0 μg∕ml) were given by TCI in group S. The target plasma concentration was adjusted to main?tain the modified Observer′s Assessment of Alertness∕Sedation Scale score of 2 or 3. The occurrence of painresponses, hypoxemia, bradypnea and∕or apnea was recorded during operation. The total amount of propofolconsumed was calculated. Results There was no significant difference in the incidence of pain response,hypoxemia, bradypnea and∕or apnea, and total amount of propofol consumed between the two groups (P >0?? 05). Conclusion Remifentanil?propofol TCI provides similar sedative and analgesic efficacy to that a?chieved by sufentanil?propofol TCI in the patients undergoing local anesthesia.

Objective To explore the possibility of the inner vertical outer spiral complex tubular urethra scaffold vascularization in repairing long segment of urethral defect.Methods From August 2014 to October 2015,27 clean male New Zealand white rabbits were divided into 3 groups,S1 group was transfected recombinant vascular endothelial growth factor(VEGF) gene lentiviral vector group.S2 group was vascular pedicle transfer tube group.C group was simple stent group.A 3.0 cm inner vertical outer spiral complex scaffold was constructed by using the small intestine acellular matrix (SIS) and polylactic acid copolymer (PLGA) modified by type Ⅰ collagen surface,and adipose-derived mesenchymal stem cells (ADSC) and smooth muscle cells after transformation from New Zealand white rabbits.In S1 group,the seed cells were transfected by recombinant vascular endothelial growth factor (VEGF) gene lentivirus,which express VEGF protein.The complex scaffold was used to repair 3.0 cm rabbit urethral defect In S2 group,the untransfected cells were seeded into the scaffold and embedded in the skin near the groin artery 3 weeks for repairing urethral defect with vascular pedicle transfer tube.In group C,the unseeded scaffold was used to repair the urethral defect alone.Postoperative observation and urethrography were followed 4,8 and 24 weeks after implantation.The HE staining,fluorescence tracing,immunohistochemical and scanning electron microscopy were evaluated at the same phase.Results In S1 group,there were one urinary fistula and one urethral stricture-related death,respectively.The urethra was smooth and patent,histological examination showed active hyperplasia of urethral capillary.In S2 group,there were one urinary fistula and two urethral stricture-related deaths,respectively.The urethral was rough,local thinning or dilated.Fat accumulation and mucosal contraction were found in the urethral submucosal,respctively.In C group,there were one urinary fistula,three hypospadias,and three urethral stricture-related deaths.The thickness of the urethra was uneven and stricture bending.The urethral mucosa was poorly repaired and the scar was narrow.HE and CD31 staining showed that S1 and S2 groups were active in the proliferation of urethral capillaries,and the angiogenesis was abundant.VEGF staining showed that the cytoplasm of endothelial cell layer,smooth muscle layer of vascular wall and the urothelial epithelial cell layer were fully expressed at 24 weeks,especially in epithelial cell layer.CKpan staining showed that the epithelium of S1 and S2 group developed to stratified epithelium,and the morphology of urethra was similar to normal urethra at 24 weeks.The urethral epithelial in C group of grew poor as single-level,irregular arrangement,24 weeks is still a lack of effective stratified epithelium.HE and oα-SMA staining showed that the smooth muscle and actin gradually increased in group S1 and S2,α-SMA staining in group C was scarce and increased at 24 weeks.PLGA was encapsulated by the surrounding tissue and the structure of electrospinning was clear after 4 weeks,absorbed and degraded after 8 weeks and absorbed after 24 weeks.Conclusions The inner vertical outer spiral comnplex tubular urethra scaffold maybe a reasonable method in repairing long segment urethral defects,and the methods of tubular urethra scaffold vascularization by transfected VEGF gene recombinant lentiviral vector and vascular flap deserve more research.

Objective To explore the influence of the killer cell immunoglobulin like receptor (KIR) gene polymorphism on cytomegalovirus (CMV) infection and pathogenesis after hematopoietic stem cell transplantation (HSCT).Methods The KIR genotype was determined by sequence-specific primer polymerase chain reaction (PCR-SSP) in 138 pairs of donors and recipients before HSCT during October,2005 and May,2011.Posttransplant monitoring for CMVpp65 antigen was performed by indirect immune histochemically assays since week 2 after transplantation.The differences between CMV positive group and negative group,inhibitive and active KIR of donors and recipients,and KIR haplotype frequency of donors and recipients were analyzed.Results There were no significant differences in frequency of KIR gene and haplotype AA,AB,BB between the donors and recipients.The frequencies of 2DS2 and 2DS4 * 003-007 of donors in CMV positive group were obviously lower than those in CMV negative group with significant differences(8％ vs 16％,P =0.0420;3％ vs 13％,P =0.0050).There was no significant difference in KIR gene between CMV positive group and CMV negative group.The CMV infection rates of haplotype AA,BB,AB donors were 64.38％,36.84％ and 50.00％,while CMV infection rates of haplotype AA,BB,AB recipients were 53.73％,46.15％ and 51.72％,respectively.The CMV infection rate was higher in the patients received KIR haplotype AA donor than in those received KIR haplotype BB donor (36.84％ vs 64.38％,P =0.0299).2DS4 * 003-007 and haplotype BB of donor were found associated with CMV infection in multifactor analysis.Conclusion KIR genotypes of donors are associated with CMV infection after HSCT.

OBJECTIVETo detect potential mutation in a large Chinese pedigree affected with congenital corneal dystrophy.

METHODSTwo patients from the pedigree were subjected to whole exome sequencing to determine the candidate gene. Suspected mutation was verified in 13 additional members by directional Sanger sequencing. Ccorrelation between genotype and phenotype was explored.

RESULTSA missense mutation, c.1877A>C (p.His626Pro), was detected in exon 14 of the TGFBI gene in 8 patients from the pedigree, but not in five unaffected members and 100 unrelated healthy controls. Respectively, the mutation was predicted as "affecting protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and MutationTaster.

CONCLUSIONThe c.1877A>C mutation of the TGFBI gene probably underlies the disease in this pedigree.

Objective·To analyze and explore the influencing factors that lead to cognitive deterioration in individuals with elevated fasting blood glucose(FBG)and the metabolic clues associated with changes in the risk of cognitive deterioration.Methods·Data from the Alzheimer's Disease Neuroimaging Initiative(ADNI)database were downloaded,and the samples with FBG and follow-up data were selected from the database.Clinical information,including age,gender,body mass index,education years,apolipoprotein E4(APOE4)genotype and race,and corresponding metabolic indicator data,including amino acids,fatty acids,proteins and others were obtained.Based on the FBG levels and diagnosis of cognitive impairment stages in Alzheimer's disease,the subjects were categorized into four groups:normal FBG without/with cognitive deterioration,and elevated FBG without/with cognitive deterioration.The univariate analysis method,the Cox proportional hazards model,orthogonal projections to latent structures discriminant analysis(OPLSDA),and Spearman correlation analysis were employed for data analysis.Results·A total of 1 317 subjects were included,among which 1 153 had normal FBG level(>3.9 mmol/L and<6.1 mmol/L)and 164 had elevated FBG level(≥6.1 mmol/L).In the normal FBG group,275 subjects showed cognitive deterioration,while in the elevated FBG group,53 subjects showed cognitive deterioration.Univariate analysis revealed significant differences in gender and race between the normal FBG and elevated FBG group,and significant differences in age,gender,and APOE4 genotype between the groups with and without cognitive deterioration(all P<0.05).Cox regression analysis indicated that primary influencing factors for cognitive deterioration were APOE4 positivity,elevated FBG,and increasing age in order(HR=2.22,HR=1.38,HR=1.02;all P<0.05).In the analysis of baseline metabolic indicators in the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels,the results of the analysis of variance revealed that in the cognitively deteriorated population,the ratio of phospholipids carried by high-density lipoproteins(HDL)to total lipids was significantly higher;low-density lipoprotein(LDL)particle concentration and the lipids carried by LDL were significantly higher after cognitive deterioration.Correlation analysis showed that valine and leucine were significantly correlated not only with FBG level but also with phosphorylated tau(pTau)level in the plasma in the cognitively deteriorated population.Cholesterol and the ratio of phospholipids to total lipids carried by HDL were significantly correlated with pTau levels in cerebrospinal fluid(CSF).Conclusion·Compared to the individuals with normal FBG level,those with high FBG level have a significantly higher risk of cognitive deterioration.Additionally,different metabolic indicators show significant differences between the groups without and with cognitive deterioration,as well as metabolic indicators before and after cognitive deterioration at different FBG levels.Overall,LDL and its lipid content,and HDL-carried phospholipids show an increasing trend during cognitive deterioration,and the branched-chain amino acids valine and leucine are significantly correlated with pTau levels in CSF and plasma,suggesting that these metabolic markers may play an important role in cognitive deterioration.

Objective To preliminarly investigate the application value of Pipeline embolization device ( PED ) in the endovascular interventional treatment of complex intracranial aneurysms. Methods From July 2015 to October 2016, the clinical data of 10 consecutive patients with complex intracranial aneurysm treated with PED at the Department of Neurosurgery, Guangdong General Hospital were enrolled retrospectively. Their surgical modalities,complications,and imaging findings were analyzed. Results Of the 10 patients,7 were females and 3 were males,their age was 32-68 years ( mean age 54 ± 12 years) . There were 8 patients with internal carotid artery aneurysm,1 with middle cerebral artery aneurysm,and 1 with vertebrobasilar artery aneurysm;there were 2 patients with ruptured aneurysm and 8 with unruptured aneurysm;there were 5 patients with saccular aneurysm ( 2 with wide-necked aneu-rysm) ,3 with fusiform aneurysm,2 with dissecting aneurysm;there were 2 patients with medium aneurysm ( diameter>5-15 mm) ,2 with large aneurysm ( diameter>15-25 mm) ,6 with giant aneurysm ( diameter>25 mm) ,and there were 2 patients with recurrent aneurysm. They were all single aneurysms. Three patients were treated with PED in combination with coil embolization,and 7 patients were treated with PED implantation alone. Nine patients were treated with one PED and 1 was treated with 3 PEDs. The immediate postoperative angiography revealed that the contrast agents in the aneurysm cavities were obviously stranded. One patient died after procedure and 1 had quadriplegia after procedure,and the remaining 8 patients had no PED-related complications. The modified Rankin scale score was 0 in 8 cases,5 in 1 case,and 6 in 1 case on the first post-operative day. They were followed up for 14 to 28 months. Conclusions The different types of intracranial aneurysms treated with PED implantation is relatively safe and effective,but there are also some risks of dis-ability and death. Strictly selecting the indications and developing the individualized treatment strategies are needed.