Objective To observe effect mechanism of L-arginine (L-arg,a precurory substance of nitric oxide sythesis) in proveting proteinuria in adriamycin-induced nephrosis model of rats.Methods Nephrosis model of 16 rats was established by tail vein injetion with adriamycin,then the 16 rats were divided into two groups;model group and treatment group with L-arg administration (treated group),the levels of nitric oxide(NO),endothelin-1(ET-1),renal function,and pathological changes were observed in the two groups.Results The successful nephrosis model of rats was indentified with optical and electron microscope technique.Proteinuria was occurred in the two groups,but proteinuria degree in treated group was lighter than those of model group,however NO level was higher than that of model group,there was negatively correlation in the levels of NO and ET-1 between both groups,pathological alteration under electron microscope observation was obviously less in the treatment group than those of the model group.Conclusions On basis of these findings,author consider that the L-arg could reduce proteinuria output by promoting NO synthesis and suppress the ET-1 production.

Objective To obtain alpaca single domain antibody targeting Her2.Methods An alpaca was immunized with human recombination Her2 protein mixed with Freund's adjuvant.Total RNA was extracted from the alpaca's blood and was used to synthesize first strand cDNA.Single domain antibody variable region (VHH) gene of the alpaca was amplified by PCR and cloned into pMES4 vector for library construction.After screening, E.coli BL21 (DE3) was transformed with selected clones and was induced with IPTG for the expression of recombinant proteins.The nanobody was purified by nickel ion affinity chromatography column.The affinity of the nanobodies to Her2 was tested.Results After the second round of screening, two antibody clones were selected, H3 and H5.The affinity of H5 was 8.106×10-10mol/L.Histochemistry results showed that H5 could recognize Her2 antigen in breast tumor tissue.Conclusion An Her2 specific nanobody derived from alpaca is obtained through phage display library screening, which can recognize human Her2 antibody in human breast tumor tissue.

Objective To evaluated the efficacy of biomarker?guided concurrent chemoradiotherapy in unrescetable esophageal squamous cell carcinoma patients. Methods 54 cases of unrescetable esophageal squamous cell carcinoma were enrolled in the prospective non?randomized clinical study and divided into study group and control group. All cases were treated with concurrent chemoraditherapy. Intensity?modulated radiation therapy was used with a dose of 60?66 Gy. Chemotherapy was perfromed on day 1 and d29. In the study group the selection of the chemotherapy drug was based on the excision repair cross?complementation 1 ( ERCC1) ,thymidylate synthetase ( TYMS) ,ribonucleotide reductase M1( RRM1) ,and theβ?tubulin isotypeⅢ( TUBB3) mRNA expression levels. In the control group,the regiment for chemotherapy was Cisplatin plus Fluorouracil. The objective response rate and overall survival ( OS ) were calculated using Kaplan?meier method and log?rank test was used for between?group comparison. The survival rate was calculated using Kaplan?Meier method and analyzed using log?rank method, other comparison was performed by χ2 test. Results The follow?up rate was 100% in the study group and 96% in the controll group. The objective response rate of the study group and the control group were 85% and 86 ( P=0. 483 ) , respectively. The median survival time ( MST) in the study group was 35. 5 months and that in the control group was 25. 8 months. The 1?,2?,and 3?year OS rates of the study group and the control group were 84%,68%,46% and 71%,59%,28% respectively (P=0. 047).No significant differences were observed in the incidence of side?effects in the two groups. Conclusions Selecting the chemotherapy drug according to biomarker,combined with radiation therapy,could improve survival.in unrescetable esophageal squamous cell carcinoma. The value needs further investigation.

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.

Objective To investigate the expression of CYP2W1 in gastric cancer and its effect on proliferation and invasion.Methods CYP2W1 protein expression in 326 gastric cancertissues and in the corresponding normal gastric mucosa was measured by immunohistochemstry.The expression of CYP2W1 mRNA in 10 randomly chosen gastric cancer tissues and its corresponding normal gastric mucosa was tested by semi-quantitative RT-PCR.4 groups pairs of gastric cancer and normal gastric mucosa cell lines were constructed.CYP2W1 expression in each of the cell line was tested.The effect of CYP2W1 expression on the proliferation and invasion capacity of the gastric cancer cells was studied by MTT experiment and transwell cell experiment.Results Expression of CYP2W1 protein in the gastric cancer tissues is higher than that in normal gastric mucosa (26.7％ vs.0,x2 =100.396,P ＜ 0.05).CYP2W1 mRNA in the gastric cancer tissues is higher than that in normal gastric mucosa [(0.413 ± 0.026) vs.(0.074 ± 0.005),t =28.115,P ＜ 0.05].CYP2W1 protein expression in the gastric cancer cell lines is higher than that in normal gastric mucosa cell lines [(0.481 ± 0.024) vs.0,t =49.097,P ＜ 0.05].The growth capacity of CYP2W1 positive gastric cancer cell is stronger than that of CYP2W1 negative cells (P ＜ 0.05),and CYP2W1 positive gastric cancer cells are also more of invasiveness,[(63 ±8) vs.(18 ±3),t =24.134,P ＜0.05].Conclusions CYP2W1 is only expressed in the gastric cancer tissues,hence it is closely related to the growth multiplication,and invasiveness of gastric cancer cells.

To investigate the anti-vasculature effects and the anti-glioma effects of attenuated Salmonella typhimurium vaccine strain expressing VEGFR2 (flk-1) gene, plasmid pcDNA3.1-flk1 was constructed and electro-transfected into live attenuated Salmonella typhimurium strain SL7207. Mouse models of intracranial G1261 glioblastoma were treated with an orally administered attenuated Salmonella typhimurium expressing flk-1 gene. The survival period was recorded and vessel density was observed by immunofluorescence. CTLs activity was measured by MTT assay. Our results showed that attenuated Salmonella typhimurium vaccine strain expressing flk-1 gene could significantly inhibit glioblastoma growth, reduce vessel density, prolong the survival period and improve the survival rate in these mice. The flk-1 specific CTLs activity was increased obviously after the vaccination. Our study showed that attenuated Salmonella typhimurium vaccine strain expressing flk-1 gene could break peripheral immune tolerance a in glioma gainst this self-antigen and kill endothelial cells by the orally administered vaccine and can be used for both prophylactic and therapeutic purposes.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Brain Neoplasms ; blood supply ; therapy ; Female ; Glioma ; blood supply ; therapy ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; Salmonella Vaccines ; immunology ; pharmacology ; Salmonella typhimurium ; immunology ; Transformation, Genetic ; Vaccines, Attenuated ; genetics ; immunology ; pharmacology ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; immunology

Objective To compare endoscopic stenting with surgery for pyloric obstruction caused by unresectable gastric cancer.Methods Between June 2002 and June 2012,6 patients underwent endoscopic stenting and 70 did surgery for gastric outlet obstruction caused by gastric cancer.Results There were no significant difference in technical success rate and clinical success rate between the stenting and surgery groups (P ＞ 0.05).The stenting group had shorter time to oral intake,and shorter length of hospital stay [(2.5-± 3.1) d vs.(6.6 ± 3.5) d,t =-7.0,P ＜ 0.001].The incidence of early complications was significantly higher in the surgery group.However,the rates of late complications were significantly lower in the surgery group.Moreover,the surgery group was significantly associated with a longer patency duration [(295.8 d,95％ CI:260.7-330.8) vs.(168.2 d,95％ CI:134.7-201.7 d),P ＜0.001] and overall survival [(307.6 d,95％ CI:272.4-342.8 d) vs.(229.6 d,95％ CI:195.1-264.3 d),P =0.003].Conclusions Both endoscopic stenting and surgery are effective palliative therapy for gastric outlet obstruction caused by gastric cancer.Endoscopic stenting is associated with better shortterm outcomes.Surgery is preferable to ES in longer patency duration.

Gut microbiota is involved in the physiological,biochemical and pathological processes of the body.It could participate in the immunoregulation and the development of enteric nervous system,prevent the invasion of pathogens,maintain normal bowel movement and inhibit the occurrence of tumor.Gut microbiota dysbiosis may also cause many diseases,such as inflammatory bowel disease,obesity and diabetes.A variety of diseases can affect gut microbiota with different ways.In addition,remote organs play a counteractive rule to gut microbiota.Maintaining the balance of the bacteria sets different requirements in different disease processes.This paper reviewed the advanced progression of gut microbiota dysbiosis after cholecystectomy and provided a new therapeutic target for gallbladder diseases.

Objective:To explore the effect of acute kidney injury(AKI)on near-term survival after lung transplantation(LT)in patients with idiopathic pulmonary fibrosis(IPF).Methods:Through consulting electronic medical records, anesthetic modes and Chinese Lung Transplant Registration System, clinical data are retrospectively reviewed for 275 IPF patients undergoing LT at Affiliated Wuxi People's Hospital of Nanjing Medical University from January 2017 to April 2021.According to the diagnostic criteria of Kidney Disease: Improving Global Outcomes(KDIGO), they are divided into two groups of AKI(169 cases)and non-AKI(106 cases).Perioperative findings of two groups are recorded.Then univariate and multivariate Cox regression models are employed for determining whether or not inter-group differences existed in survival rates post-LT.Also AKI is staged according to the KDIGO.And the effect of stage 1/2/3 AKI on near-term postoperative prognosis is examined.Results:The differences are significantly different in recipient gender, creatinine, 6-minute walking test, forced vital capacity(FVC), lung allocation score, oxygenation index, N-terminal pro-brain natriuretic peptide(NT-Pro BNP), preoperative hormone use and volume of crystal infusion( P<0.05).After multivariate Cox regression correcting for covariates, no statistical significance exists in effect of AKI stage 1 on near-term postoperative survival rate( P<0.05).AKI stage 2/3 still has statistical significance in risk of mortality at Day 30/90/180/365 post-operation( P>0.05). Conclusions:As a common complication post-LT, AKI significantly affects near-term postoperative prognosis of transplant IPF patients.Stage 2/3 AKI impacts near-term postoperative survival while stage 1 AKI is not associated with higher mortality.

Objective:To investigate the clinical manifestation, genetic characteristics, treatment and prognosis of Crouzon-like syndrome.Methods:Clinical data of one case of Crouzon-like syndrome diagnosed in Children′s Hospital Affiliated to Zhengzhou University in May 2019 were collected, including clinical test, treatment plan, follow-up outcomes. The clinical characteristics and the mutation characteristics of IL11RA-related Crouzon-like syndrome were analyzed combined with the literature.Results:The male proband, five years and four months old, was admitted with the main clinical manifestations including headache, vomiting, exophthalmos, ocular hypertelorism, nasal root flat and scaphocephaly. CT showed that the cerebellar tonsil moved down slightly, the occipital magnum was full, the bilateral cranial plates were locally thinner, the bilateral cranial diameters were increased, and the cranial seams were closed. Magnetic resonance imaging showed ChiariⅠmalformation. The mutation c.40_63del and splice site mutation c.811-2A>G of the patient′s IL11RA gene were screened by whole exome sequencing. Sanger sequencing showed that the mutations are compound heterozygous and both are first reported. The mutation c.811-2A>G was derived from the patient′s mother, and the other one is de novo.Conclusions:The main clinical manifestations of Crouzon-like syndrome are craniosynostosis and midface hypoplasia and ocular deformity. The study identified two novel mutations in the Crouzon-like syndrome related IL11RA gene. Genetic sequencing is helpful for accurate diagnosis and timely surgical treatment.