Background and purpose:Radiotherapy has been the preferred method for the treatment of naso-pharyngeal carcinoma (NPC). The aim of this paper was to compare the dosimetric differences in target volume and organ at risk between simpliifed intensity-modulated radiation therapy (sIMRT) and intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma.Methods:Treatment plans for ten NPC cases were designed with the same dose prescription and objective by means of IMRT and sIMRT respectively. Compare:(1) Plan dosimetric dis-tribution, conformity index (CI) and homogeneity index (HI) of the targets, the dosimetric parameters of organ at risk (OAR); (2)The total monitor units (MU) and the total segments.Results:The CI and HI of the planning gross tumor volume(PGTV) were 0.647 and 0.057 (IMRT), 0.633 and 0.071 (sIMRT), respectively (t=2.14,P=0.062;t=-6.21, P=0.000). Compared to IMRT, sIMRT had less inferior target homogeneity. However both treatment plans could achieve the clinical dosimetric demands. There was no signiifcant difference between IMRT and sIMRT in protecting OAR (t=-0.51-2.22,P=0.053-0.621). The sIMRT plan was better than IMRT plan in total MU and total segments. Conclusion:sIMRT is slightly inferior to IMRT in terms of target homogeneity, with similar target conformity and OAR dosimetric parameters. The sIMRT plan can reduce total monitor units and total segments. Thus it provides a clinical solution with high effciency for radiotherapy center with a large number of patients.

Objective To investigate the effects of JNK inhibition on insulin signaling pathway. Methods HepG2 cells were treated with different kinds of JNK inhibitors for 12 h, and then the cells were treated with 10 nmol/L insulin for 5 min to stimulate insulin signaling pathway. Mitogen-activated protein kinases ( MAPK ) and insulin signaling pathways were analyzed by Western blot using the total cell lysates. Results JNK activity was significantly inhibited by JNK inhibitor JNKi-Ⅷand results showed that JNKi-Ⅷtreatment could reduce insulin signaling pathway in a dose-dependent manner. Furthermore, other JNK inhibitors including JNKi-Ⅴ, JNKi-Ⅲ, and SP600125 blocked JNK activity in HepG2 cells. Similar to JNKi-Ⅷ, these JNK inhibitors also impaired insulin signaling transduction in a dose-dependent manner. Conclusion In HepG2 hepatocytes, JNK activity inhibition blocks insulin signaling transduction.

Objective To explore the feasibility of establishing porcine model for training of endoscopic ultrasound (EUS) guided celiac plexus paracentesis.Methods A total of 6 healthy pigs were sedated with an intramuscular injection of Ketamin at 10 mg/kg,followed by intravenous injection of 3% pentobarbital at 0.8 ml/kg.EUS was then performed and empty seeds were implanted into celiac plexus.Enhanced CT scan was performed to confirm the location of the implanted seeds.Results No animal died after the procedure.All seeds were accurately distributed on both sides of the celiac trunk except in one pig the seed was found in stomach by CT scan and was re-implanted another day.Conclusion Pigs are similar to human in anatomic structure and they can be excellent models for beginner endoscopy physicians to acquire the skill of EUS guided celiac plexus paracentesis.

Objective To evaluate the influence of brachytherapy with 125Ⅰ seeds on celiac ganglia in porcine models. Methods Twelve pigs were randomly assigned into 3 groups to accept celiac plexus block by bilateral injection with 2 non-radioactive seeds in group A (n = 4), 0.4 mCi seeds in Group B (n = 4) and 0.8 mCi seeds in Group C (n = 4), respectively. Prophylactic antibiotics were administered postoperatively. Enhanced CT and three-dimensional reconstruction of blood vessels were performed to confirm the proper placement of the seeds. The animals were sacrificed 14 days and 60 days after the procedure, and TUNEL assay was employed to study neuron apoptosis in ediac ganglia. Results The procedure was succossfully performed in,10 pigs(83.3%)and failed in two others. The rescue procedure was performed on the day after and succeeded in both pigs. Apoptosis of neurons significantly increased in brachytherapy groups than in the control group and it was positively correlated with dose and time of radiation. Conclusion Brachytherapy can cause apoptosis of neurons of celiac ganglion, which could be the basis of its clinical application.

ObjectiveTo assess the safety of celiac plexus brachytherapy with 125Ⅰseeds placementguided by endoscopic ultrasound in porcine model, and to evaluate its effect on surrounding vessels and organs.MethodsFourteen pigs were randomly divided into 4 groups to accept celiac plexus block by bilateral injection with 2 non-radioactive seeds in group A (n=4),0.4 mCi seeds in Group B (n=4),0.8 mCi seeds in Group C (n=4) and one lateral injection with 5 ml dehydrated alcohol,respectively.Abdominal X-ray,Enhanced CT and three-dimensional reconstruction of blood vessels were performed to confirm the proper placement of the seeds in group A,B and C.Routine blood test,liver and renal function,serum amylase and CD4+/CD8+ratio were examined preoperatively and at the end of the follow-up in all groups.Animals were euthanized in batch to observe the position of the implanted seeds.Tissues and organs around the seeds were dissected for pathological examination.ResultsThe procedure succeeded in 12 pigs (85.7%)and failed in two others (1 in group A,and 1 in C) due to inappropriate position.Rescue procedures were performed on another day and succeeded.No significant difference was found in routine blood test,liver and renal func-tion,serum amylase and CD4+/CD8+ratio,except WBC elevation and small abcesses were found 7 days after the procedure in one pig of group C.In the radiated area, there was degeneration,necrosis and mild in-flammation at the outer membrane of blood vessels,with fibrosis around,which was positively correlated with the radiation dosage and duration.There was no change at the muscular layer and the innermost membrane of blood vessels,and no thrombosis was found.In group D,the celiac trunk became slightly brown and wider with obvious hemorrhage,necrosis and infiltration of inflammatory cells in the outer membrane of blood vessles and connective tissues around.ConclusionBrachytherapy has little negative effect on the organs a-round. It does not harm immunnity but induces lesions in blood vessels. Compared with dehydrated alcohol,this negative effect is limited.Therefore,celiac plexus brachytherapy with125Ⅰseeds guided by endoscopic ultrasound is safe.

Objective To assess the safety of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA)of pancreatic lesions.Methods Patients who underwent EUS-FNA of a pancreatic lesion between January 2005 and June 2007were studied retrospectively.Possible risk factors were assessed by using logistic analysis.Results In 119 patients who underwent pancreatic EUS-FNA,mild acute pancreatitis were observed in 1(0.84%)patient after the operation.No complication occurred in 12 patients with regional portal vein hypertension.Nine patients(7.6%)showed hyperamylasemia 3 h after the procedure,rangeing from 197 to 835 U/L,with an average of(327±200)U/L.Blood amylase level kept increasing 24 h postoperatively in 6 cases of the 9.Logistic regression analysis showed past history of acute pancreatitis,gender,needle size,number of puncture,cystic foci,preoperative blood amylase level and location of foci would not possibly be the risk factors of hyperamylasemia.Conclusion Incidence of complications after EUS-FNA is 0.84%,and the occurrence rate of hyperamylasemia is 7.6%,indicating,EUS-FNA is a safe procedure.

Objective To evaluate the safety and efficacy of direct celiac ganglion irradiation with 125I seeds for pain relief secondary to advanced pancreatic carcinoma (PC).Methods This study enrolled 23 consecutive patients who had moderate to severe pain resulting from advanced PC.All patients underwent EUS-guided direct celiac ganglion irradiation with 125I seeds.Follow-up was conducted at least once weekly until death.Blood parameters,Visual Analog Scale (VAS) score,mean analgesic consumption,and complications were evaluated during follow-up.Results All patients successfully underwent implantation at one attempt.The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6).Immediately after the procedure,pain relief and analgesic consumption showed no significant changes compared with preoperative values.Six patients (26％) reported pain exacerbation.Two weeks later,the VAS score and mean analgesic consumption were significantly less than preoperative values.No procedure-related deaths or major complications occurred.Conclusion EUS-guided direct celiac ganglion irradiation with 125I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.

Objective To investigate the risk factors for failure of percutaneous catheter drainage (PCD) for patients with infective pancreatic necrosis (IPN).Methods A retrospective review of medical records of patients with IPN who received PCD at Pancreatic Intensive Care Unit (PICU) of Changhai Hospital from April 2010 to June 2014 was performed.The patients were divided into 2 groups:(1) PCD success group (n =48) and (2) PCD failure group (n =12).The potential parameters for failure of PCD were recorded,which included age,sex,etiology,length of hospital stay,outcome,MCTSI,APACHE Ⅱ scores,number of organ failure,duration of use of antibiotics,duration of use of PPIs,if delayed fluid resuscitation occurred,start of enteral nutrition,nutrition status,etc,and univariate and multivariate logistic regression analysis was used.Results Univariate analysis showed MCTSI,number of organ failure,malnutrition,use of PPIs (more than two weeks),delayed enteral nutrition,delayed fluid resuscitation,the number of drainage catheter,number of aspiration,multi-drug resistant infections of drainage fluid were risk factors for failure of PCD;while multivariate logistic regression analysis showed that MCTSI (OR =3.33;95％ CI 1.52 ～ 7.29;P =0.003);multi-drug resistant infections of drainage fluid (OR =8.62;95 ％ CI 1.11 ～ 67.19;P =0.040) were risk factors for failure of PCD.Conclusions MCTSI and multi-drug resistant infections of drainage fluid can significantly influence the success rate of PCD.PCD should be carefully considered for patients with high score of MCTSI and multi-drug resistant infections of drainage fluid.

Objective To investigate the effect of needle sizes and aspiration techniques on sample quantity. Methods Aspiration was performed on porcine liver in vitro for 10 times with three different sizes of needles(19 G, 22 G and 25 G) and four different aspiration techniques[non?negative pressure(NP), 10 ml NP,20 ml NP and slow?pull], 20 mm in depth. A total of six aspirations were performed with each needle by the same aspiration technique. All the obtained specimens were fixed in formalin with the cell block method. The samples were evacuated according to our grading criteria. Results The mean±standard deviation(SD) score for 19 G,22 G, 25 G were 5?71±0?69,4?63±1?24, 3?79±1?84 respectively. The mean±SD score for methods non?NP,10 ml NP,20 ml NP and slow?pull were 4?72±1?53,4?56±1?46,4?72±1?50,4?83±1?76 respectively. The multi?analysis of variance results showed that there were statistical differences between different needles size( F=12?00,P<0?001) with 19 G being the best,followed by 22 G and the least specimen obtained by 25 G needle. There were no statistical differences among aspiration techniques ( F=0?128, P=0?943).The analysis showed that the thicker the needle was,the better sample quality was 19 G yielded to the highest quantity of specimens. The most specimens could be obtained with 19 G needle and non?NP, 22 G needle and 20 ml NP and 25 G needle and slow?pull. Conclusion In clinic, aspiration technique should be selected according to different aspiration needles. 19 G is superior to others, with non?NP method. For 22 G needle, 20 ml NP is preferred and for 25 G needle,slow?pull is preferred.

Objective:To investigate the clinical characteristics and gene variation of asparagine synthase deficiency that is caused by ASNS gene variation. Methods:In Department of Neuroendocrine Pediatrics, Affiliated Hospital of Qingdao University from October 2018 to February 2020, the clinical data of a family of asparagine synthase deficiency were analyzed retrospectively.The pathogenic mutation of the proband was screened by the full exon analysis technique.The pathogenic sites of candidate genes were determined by combining the phenotype of the proband.In the heterotopic spot of the proband, his parents and other family members were verified by Sanger sequencing.Meanwhile, the relevant literature database was consulted, and the reported ASNS mutation related cases were collected and reviewed. Results:The female with proband visited the hospital at the age of 4 months, and she had recurrent convulsions at the age of about 3 months.Physical examination showed that the child suffered from microcephaly, and mental and motor retardation.Meanwhile, video electroencephalogram examination displayed extensive moderate high amplitude spiny slow wave and sharp slow wave.Exon sequencing illustrated that the compound heterozygous variants of ASNS gene were c. 1211G>A (p.R404H) and c. 1643C>T (p.S548F), respectively.c.1211G>A was a known pathogenic variant, and c. 1643C>T was a new variant.The proband′s younger brother visited the hospital at the age of 2 months, developed convulsions at the age of 1 month, and developed mental and motor retardation.Electroencephalogram displayed that bilateral posterior head was dominant, multiple foci and extensive spike wave, and spike slow wave and fast wave were distributed.Sanger sequencing revealed the same ASNS compound heterozygous variants as the proband.Both of them died of status convulsion at the age of 7 months and 6 months, respectively. Conclusions:This study is helpful to further understand the clinical features of the disease and reveal a new pathogenic mutation of ASNS gene, so as to enrich the mutation spectrum of ASNS gene, thus providing important basis for clinical treatment and genetic counseling.