[ABSTRACT]AIM:Toestablishatransgenicheterozygousmousemodelofprecancerouslesionsofcolorectal cancer with p110δmutation in the C57BL/6J background for serving the studies on colorectal cancer research mediated by p110δ.METHODS:The transgenic heterozygous mice were generated by crossing in p110δD910A/D910A mouse and ApcMin/+mouse, and the genotype was detected by PCR .Compared with ApcMin/+mice, transgenic heterozygous mice ( ApcMin/+;p110δD910A/D910A)were counted, and the number and size of intestine polyps were analyzed after methylene blue staining . The intestinal tissue structure was assessed by HE staining .RESULTS:The transgenic heterozygous mouse model of pre-cancerous lesions of colorectal cancer with p 110δmutation was established .The number and size of polyps in the transgenic heterozygous mice were declined .CONCLUSION: A transgenic heterozygous mouse model of precancerous lesions of colorectal cancer with p 110δmutation was successfully established .The initial phenotype of intestinal tumors in transgenic mice was observed .This model will greatly contribute to the related research of colorectal cancer in mice .

Objective To investigate the feasibility and clinical effect of the tubeless minipercutaneous nephrolithotomy (PCNL) in treatment of upper ureteral calculi.Methods From March 2014 to March 2015,all the patients with upper ureteral calculi except for those with severe infection,pyonephrosis or renal cortex less than 5 mm were randomized into two groups,the standard PCNL group (24 F nephrostomy tube) and the mini-PCNL group (18 F nephrostomy tube).After PCNL,all the patients received ultrasound examination to check residual stones,perforation and urine leakage.DJ tube was placed and the channel of PCNL was packed with hemostatic sponge without nephrostomy tube.There were 26 patients in standard group and 28 in mini-group.The operation time,postoperative hemoglobin change,postoperative visual analogue pain score (VAS),the time when urine turned clean,postoperative urinary extravasation,hydrothorax,fever and the stone-free rate were compared between two groups.Particularly,these data were compared in those aged＞65 years.Results The operation time in the standard PCNL and the mini-PCNL group was (58.3 ±21.8) and (86.4±23.3) minutes respectively,and had a significant difference (t=10.836,P＜0.05).The decrease in hemoglobin level was (8.3±5.8) g/L and (7.7±0.5.4) g/L,the VAS scores was (3.8±0.8) and (3.6±1.1),the time when urine turned clean was (11.9±4.7) h and (9.6±5.6) h,the postoperative hospital stay was (5.1±0.8) d and (4.8±1.2) d,and the stone free rate was 92.3％ and 89.2％ in standard PCNL and mini-PCNL group respectively(P＞ 0.05).No significant difference were found between two groups (all P＞0.05).There was one patient who got fever more than 38.5℃ in the standard group and 2 cases in the mini-group.Each group had 1 slight hydrothorax,and no blood infusion and perinephric urinary extravasation were found.The application of packing hemostatic sponge in the nephrostomy channel was feasible and suitable for both the standard and tubeless mini-PCNL groups.Conclusions The application of packing hemostatic sponge in the nephrostomy channel is feasible and suitable in both the standard and tubeless miniPCNL.It is safe for the treatment of renal and ureteral calculi,and it can decrease the hemorrhage and urine leakage,which works for the elderly patients too.

Objective To investigate the roles of sphingosine kinasel (SPK1) in apoptosis,invasiveness and multidrug resistance of human hepatocellular carcinoma cell line BEL-FU.Methods BEL-FU cells were infected with adenovirus carrying SPK1wT gene and SPK1siRNA (Ad-H1-SPK1) gene.Their effects on biological characteristics of BEL-FU cells were evaluated by MTT,cellular SPK enzyme activity assay,Transwell Migration Technology and Western-blot,respectively.Results AdSPK1wT significantly increased SPK activity but SPK1siRNA(Ad-H1-SPK1) decreased SPK activity.Over expression of SPK1 suppressed the apoptosis induced by DMS(Dimethyl sphingosine,DMS) and enhanced migration of BEL-FU cells.The cells infected with SPK1 siRNA( Ad-H1-SPK1)significantly increased the apoptosis induced by DMS and inhibited the migration of human hepatocellular carcinoma cells.The expression of multidrug resistance-related protein (MRP1) of cells infected with SPK1siRNA (Ad-H1-SPK1) was suppressed significantly compared with the control group,while the expression of MRP1 infected with Ad- SPK1wT was enhanced.Conclusion SPK1 activity is closely associated with apoptosis、migration and multidrug resistance of human hepatocellular carcinoma cells,therefore,it may serve as a new target for HCC treatment.

Objective To evaluate the etiology and clinical features of jejunoileum bleeding.Methods Seventy-two patients admitted in 7 hospitals of Shangdong province for jejunoileum bleeding from January 1998 to December 2008 were enrolled in the study. There were 46 males and 26 females with mean age of 47 years (ranged 13-85 years). The jejunoileum bleeding was confirmed by means of endoscopy, images or surgery. The causes, diagnostic methods and major clinical manifestations were retrospectively analyzed. Results The most frequent cause of jejunoileum bleeding was tumor (42/72,58.3 %), followed by enteritis (9/72, 12.5 %), diverticulum ( 7/72, 9. 7%), angiopathy (7/72,9.7%), Crohn's disease (3/72,4.2%). Differences were significant in constituent ratio of cause of jejunoileum hemorrhage between male and female and between jejunum and ileum (P＜0.05).Hematochezia or hematochezia with abdominal pain was the first presentation. The jejunoileum bleeding in 54. 2% patients was diagnosed by laparotomy, 23. 6% by capsule endoscopy, 9.7% by selective angiography, 6.9% by small bowel series and enteroclysis, 2.8% by colonoscopy and 2.8% by push enteroscopy. The complications of jejunoileum bleeding were anemia, intestinal obstruction,peritoneal metastasis, shock, ankylenteron and intestinal perforation. Conclusions Intestinal tumor is the most common cause in jejunoileum bleeding, especially in jejunum. Whereas the enteritis,diverticulum and angiopathy were often found in ileum. The capsule endoscopy and push enteroscopy are recommended in diagnosis of jejunoileum bleeding.

Objective To explore the factors affecting the effect of first stage treatment of sacral neuromodulation.Methods A retrospective analysis of 39 patients with dysuria related diseases from April 2012 to January 2016 was performed.There were 14 male patients and 25 female patients.Their age ranged from 15 to 86 years old,mean 54 years old.The types of disease were bladder pain syndrome/interstitial cystitis in 1 8 cases,idiopathic urinal retention in 5 cases,overactive bladder in 8 cases,neurogenic bladder in 6 cases,and urgent incontinence in 2 cases.All patients were treated by behavioral therapy,drug therapy,and at least one recomnended treatment method.All previons treatments were ineffective.All patients were collected baseline medical records.The voiding diary,visual analogue pain score,quality of life score,anxiety score and other information before and after the first stage surgery and the last follow-up after the second stage surgery were also collected.Results A total of 39 patients were enrolled in this study.27 patients (69％)who were satisfied with the effect of the first stage of surgery were treated with the second stage surgery,and 12 patients (31％)who were not satisfied with the results of the first phase operation did not undergo the second phase operation.The second stage implantation rate was 69％.The average experience time was (21.6 ± 3.0) days.In the single first stage implantation group,there were 6 males and 6 females,including interstitial cystitis in 3 cases,overactive bladder in 3 cases,neurogenic bladder in 4 cases,idiopathic urinary retention in 1 cases and urgent incontinence in 1 cases.2 cases have a history of pelvic and urinary surgery and 10 cases dont.The average BMI was 21.8 ± 3.7 kg/m2,and mean age was(44.5 ± 19.1) years old.The average preoperative anxiety score was 33.7 ± 5.3 and the average pain score of preoperative was 8.0 ± 1.0.The average quality of life score was 4.6 ±0.8 and the average daily nunber of urine was 23.1 ± 12.8.The average mean urine volume was (89.4 ± 33.0) ml,the average frequency of nocturia was 10.3 ± 5.5,the average medical history time was (100.6 ± 125.5) months.In the second stage implantation group,there were 8 males and 19 females,including interstitial cystitis in 15 cases,overactive bladder in 5 cases,neurogenic bladder in 2 cases,idiopathic urinary retention in 4 cases,and urgent incontinence in 1 cases.10 cases have a history of pelvic and urinary surgery while 17 cases don't.Average BM1 was (24.1 ± 2.6) kg/m2,and mean age was(57.9 ± 16.8) years old.The average preoperative anxiety score was 27.7 ± 5.9,the average pain score of preoperative was 7.9 ± 1.6.The average quality of life score was 5.3 ± 0.9 the average daily urinary number was 30.6 ± 14.2.The average mean urine volume was (64.8 ± 37.4) ml and the average frequency of nocturia was 13.3 ± 9.2.The average history of time was (83.0 ± 56.0) months.Patients who were implanted with permanent sacral neuromodulation system were mostly older (P =0.034),with higher BMI (P =0.043) and lower anxiety (P =0.008).There were no statistically significant differences in gender(P =0.287),disease(P =0.116),the daily urinary frequency (P =0.140),the average urine volume (P =0.470),nocturia freqnency (P =0.068),pain scores (P =0.880),surgical history (P =0.276)and the medical history time (P =0.116) between patients who underwent first stage surgery only and second stage surgery.Conclusion BMI,age and anxiety may be the factors that affect the outcome of the first stage treatment of sacral neuromodulation.

Despite the deepening of research on breast cancer,improving of treatment techniques,there are still many patients will appear local-regional recurrence after surgery.For patients with local recurrence after radical mastectomy,according to whether the postoperative radiotherapy performed,prognosis and treatment protocols are absolutely different.As for patients with local recurrence after breast-conserving surgery,more and more studies have shown that lumpectomy (secondary breast conserving surgery) combined with brachytherapy can achieve a similar effect with radical surgery in recent years,so it is a worth considering treatment protocol.

Objective:To explore the expression of serum miR-224-5p in PDAC and its significance for early clinical diagnosis.Methods:From August 2018 to April 2020, 40 patients with PDAC (11 patients with early PDAC, 29 patients with advanced PDAC), 21 patients with chronic pancreatitis and 40 healthy volunteer controls admitted in Qingdao Municipal Hospital were enrolled. The level of serum miR-224-5p in each group was detected by qRT-PCR method, and the correlation with clinicopathological parameters was analyzed. The receiver-operating characteristic (ROC) curve of miR-224-5p, CA19-9 and miR-224-5p combined with CA19-9 were drawn, and the sensitivity and specificity of the diagnosis were calculated.Results:The serum miR-224-5p levels in early PDAC group, middle and late PDAC group, chronic pancreatitis group and healthy control group were 3.21(2.01, 4.60), 4.70(3.50, 8.26), 1.72(1.02, 2.78) and 1.38(0.89, 2.11), respectively; and the level of serum miR-224-5p in the middle and late PDAC group was significantly higher than that in the early PDAC group, and that in the early PDAC group was significantly higher than that in the chronic pancreatitis group and the healthy control group, and all the differences were statistically significant ( P<0.05). The sensitivity of serum miR-224-5p combined with CA19-9, miR-224-5p, and CA19-9 in the diagnosis of overall PDAC was 95.0%, 85.0% and 67.5%, respectively; and the specificity was 70.0%, 82.5% and 87.5%, respectively. The sensitivity for early PDAC was 90.9%, 72.7% and 63.6%, and the specificity was 85.0%, 72.5% and 87.5%, respectively. MiR-224-5p combined with CA19-9 has the highest specificity in the diagnosis of PDAC. The level of serum miR-224-5p in patients with PDAC was correlated with TNM stage, lymph node metastasis and distant metastasis (all P values <0.05). Conclusions:The expression of serum miR-224-5p was significantly up-regulated in patients with early PDAC, and The level of serum miR-224-5p in patients with PDAC was correlated with TNM stage, lymph node metastasis and distant metastasis. The sensitity of serum miR-224-5p and miR-224-5p combined with CA19-9 for early PDAC diagnosis were superior to CA19-9 alone, which can be used as a potential sensitive biological marker for early screening of PDAC.

Objective To investigate the expression level of serum miR-486-5p in patients with pancreatic cancer and the value of serum miR-486-5p combined with carbohydrate antigen 19-9 (CA19-9) in predicting the resectability of pancreatic cancer. Methods A total of 60 patients who were diagnosed with pancreatic cancer in Qingdao Municipal Hospital from September 2018 to December 2020 were enrolled, among whom 32 patients had resectable or borderline resectable pancreatic cancer (operable group) and 28 had unresectable pancreatic cancer (non-operable group), and a benign pancreatic disease group with 30 patients and a healthy control group with 44 individuals were also established. Quantitative real-time PCR was used to measure the serum level of miR-486-5p in each group, and the relative expression level of miR-486-5p was calculated to analyze its association with the clinical features of pancreatic cancer, including age, sex, tumor location, tumor size, TNM stage, lymphatic metastasis, and distant metastasis. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups, and the chi-square test was used for comparison of categorical variables. The receiver operating characteristic (ROC) curve was plotted, and a binary logistic regression analysis was used to calculate the combined predictive value and then investigate the value of serum miR-486-5p combined with CA19-9 in predicting the resectability of pancreatic cancer. Results The relative expression level of serum miR-486-5p in the operable group [2.16 (1.38~3.30)] and the non-operable group [4.65 (2.80~9.90)] was significantly higher than that in the benign pancreatic disease group [1.01 (0.52~1.53)] and the healthy control group [0.99 (0.24~1.01)] (all P < 0.001). There were significant differences in the number of patients with low or high expression of miR-486-5p between the patients with different TNM stages, presence or absence of lymphatic metastasis, and presence or absence of distant metastasis ( χ 2 =13.765, 5.157, and 6.638, all P < 0.05). Compared with CA19-9 alone, miR-486-5p+CA19-9 had a significantly better value in distinguishing the operable group from the benign pancreatic disease group (area under the ROC curve [AUC]=0.87, 95% confidence interval [ CI ]: 0.760-0.942; with a sensitivity of 81.3% and a specificity of 83.3%), distinguishing the operable group from the healthy control group (AUC=0.92, 95% CI : 0.836-0.970; with a sensitivity of 90.6% and a specificity of 86.4%), and distinguishing the operable group from the non-operable group (AUC=0.94, 95% CI : 0.884-0.998; with a sensitivity of 85.7% and a specificity of 93.7%) ( Z =2.841, 2.510, and 2.387, all P < 0.05), and the optimal cut-off values were 3.12, 3.21, and 6.63, respectively. Conclusion MiR-486-5p can be used as a serum biomarker for the diagnosis of pancreatic cancer, and miR-486-5p combined with CA19-9 has a better clinical value than CA19-9 alone in predicting the resectability of pancreatic cancer in the patients with benign pancreatic diseases and the healthy population.