Objective:To analyze the clinical characteristics of patients with de-novo non-alcoholic fatty liver disease (de-novo NAFLD) and patients with de-novo NAFLD combined with metabolic syndrome (MS) after liver transplantation (LT) , and to determine the related risk factors.Methods:Patients who underwent LT at the Organ Transplantation Center, the Affiliated Hospital of Qingdao University, from Jan. 2016 to Oc. 2020 and were monitored until Oct. 2021 were gathered. The recipients were divided into the group with/without de-novo NAFLD, and LT recipients with de-novo NAFLD were divided into the group with/without combined MS. Clinical characteristics of the LT recipients with de-novo NAFLD combined with MS were analyzed. Logistic regression analyses were performed to identify the risk factors for LT recipients with de-novo NAFLD and those with combined MS.Results:A total of 324 LT recipients with a median follow-up of 2.9 years (range: 2.0-4.3 years) were included in the study. De-novo NAFLD was diagnosed in 21.0% (68/324) of the LT recipients, and MS was diagnosed in 44.1% (30/68) of these patients. Compared with LT recipients without de-novo NAFLD, those with de-novo NAFLD had higher preoperative body mass index (BMI) , blood glucose, glycated hemoglobin levels and lower platelet levels, and longer postoperative follow-up, higher BMI, waist circumference, albumin, triglycerides (TG) , low-density lipoprotein (LDL) , blood glucose, glycated hemoglobin levels, and the incidence of MS (all P<0.05) . Preoperative platelets, glucose, postoperative albumin, LDL and BMI were independent risk factors for predicting de-novo NAFLD after LT (all P<0.05) . Preoperative glucose performed well in predicting the occurrence of de-novo NAFLD (threshold: 5.5mmol/L, P<0.001, AUC=0.678) . The differences in Pre-LT blood glucose, post-LT BMI, waist circumference, prevalence of prediabetes or diabetes, fatty liver index (FLI) , and NAFLD fibrosis score (NFS) between de-novo NAFLD LT recipients with and without combined MS were significantly different (all P<0.05) . Conclusions:The incidence of de-novo NAFLD after LT is noteworthy, and LT recipients with de-novo NAFLD are more likely to have a combination with MS. In preoperative treatment, keeping blood glucose to 5.5 mmol/L or below trends helps to lower the risk of de-novo NAFLD following LT. LT recipients’ nutritional state and lipid levels require prompt care. High albumin levels might not be a desirable thing. De-novo NAFLD LT recipients with concomitant prediabetes or diabetes may imply an increased risk of developing comorbid MS during the post-LT follow-up. Controlling FLI levels in LT recipients with de-novo NAFLD may reduce the risk of developing comorbid MS.

Objective:To explore the clinical applications and therapeutic outcomes of immune checkpoint inhibitors(ICIs)on liver transplantation(LT)recipients after tumor development.Methods:Eight databases including PubMed, China National Knowledge Infrastructure, Wanfang Data, CQVIP, PubMed, EMBASE, Web of Science and Google scholar were accessed for searching the relevant literature articles in both Chinese and English from the establishment of databases to December 31, 2021. Disease response, adverse reactions and prognoses of patients with malignant tumors after LT and receiving ICIs were analyzed.Results:The patient was diagnosed as chronic rejection plus drug-induced liver injury by liver biopsy. After intermittent treatment with DPMAS plus plasma exchange and immunosuppressants, he finally died of tumor recurrence at 37 months after LT. After screening, a total of 28 articles on the application of ICIs after LT were retrieved. In these articles, there were 47 patients(37 males and 10 females)with a median age of 57(14-71)years and the predominant type of tumor after LT was hepatocellular carcinoma(28/47, 59.6%), followed by malignant melanoma in 11 cases (23.4%), non-small cell lung cancer in 3 cases(6.4%), colorectal cancer, cholangiocarcinoma, squamous cell carcinoma, hypopharyngeal squamous cell carcinoma and post transplant lymphoproliferative disease(PTLD) in 1 case(2.1%). The overall remission rate after ICI treatment was 29.8%(14/47)and the disease progression rate 68.1%(32/47). Among them, 31.9%(15/47)had immune rejection. Case fatality rate was 61.7%(29/47)and median survival time 6.5(0.3-48.0)months.Conclusions:Depending on existing publications, among those LT recipients with malignant tumors treated by ICIs, the rate of graft rejection and patient mortality are higher. ICIs should be carefully considered for LT patients and further researches are required.

Objective To analyze the incidence and risk factors of colorectal adenomatous polyps (CAP) in recipients after liver transplantation. Methods Seventy-seven liver transplant recipients and 231 individuals undergoing colonoscopy during physical examination were recruited in this study. The incidence of CAP and pathological examination results were analyzed. Clinical data of liver transplant recipients were collected. According to the incidence of CAP, liver transplant recipients were divided into the CAP group (n=28) and non-CAP group (n=49). The risk factors of CAP after liver transplantation were identified. Results The 5-year cumulative incidence rates of colorectal polyps in liver transplant recipients and physical examination individuals were 43% and 34%, and 29% and 23% for the 5-year cumulative incidence rates of CAP, with no significant differences (both P > 0.05). Among all liver transplant recipients, 65 polyps were detected. The quantity of polyps in 1 case was excessively high and not counted. Multiple polyps were identified in certain recipients. Five polyps were not prepared for pathological examination due to small size. Pathological examination of 60 polyps demonstrated 25 inflammatory polyps, 33 CAP (8 complicated with low-grade intraepithelial neoplasia and 3 complicated with high-grade intraepithelial neoplasia), and 2 well-differentiated adenocarcinoma. Cox model analysis prompted that use of ciclosporine after liver transplantation was an independent risk factor for CAP in the recipients. Conclusions The risk of CAP is slightly elevated after liver transplantation. Postoperative use of ciclosporine is an independent risk factor for CAP in recipients after liver transplantation. Colonoscopy should be emphasized in the recipients after liver transplantation.

Objective To investigate the incidence of de novo malignant tumors of the digestive system after liver transplantation (LT) in China. Methods Relevant literature review was performed from Wanfang data, China National Knowledge Infrastructure (CNKI) and Chongqing VIP. The retrieval time started from the establishment of each database to May 9, 2019. The Chinese search terms were liver transplantation+ postoperative/de novo+ malignant tumor/cancer. The age distribution, sex composition, time of diagnosis, involved organs, treatment and clinical prognosis of recipients with de novo malignant tumors of the digestive system after LT in China were retrospectively analyzed. Results After literature screening, 16 articles were eventually selected including 47 cases of de novo malignant tumors of the digestive system after LT. A majority of them were male recipients. The age of the recipients was 51 (23-65) years old, most of them were middle age (45-59 years old). The average time of diagnosis of de novo malignant tumors of the digestive system after operation was 43 (2-156) months, with the highest number of cases within postoperative 1-3 years. Colon and stomach were the most common tumor sites. Surgery combined with radiotherapy and chemotherapy remained the main treatment option. However, the overall clinical prognosis of patients with de novo malignant tumors of the digestive system after LT was poor with a mortality rate of 51%. Conclusions In China, colon cancer and gastric cancer are the main de novo malignant tumors of the digestive system after LT. The overall clinical prognosis of patients with de novo malignant tumors of the digestive system is poor. Sufficient attention should be paid to postoperative monitoring and prevention.

Objective:To summarize the experience of diagnosing and treating de novo gastric cancer after liver transplantation(LT).Methods:The clinical data were analyzed for 3 LT patients with de novo gastric cancer during follow-ups.Results:The mean diagnostic age was 57(47~67)years, mean time interval between LT and diagnosis of de novo gastric cancer 82(40~122)months and mean follow-up time 23(4~42)months. After surgical resections, 2 survived and another died of recurrence.Conclusions:LT recipients are recommended for regular screening of de novo malignancies. Regular endoscopic screening of gastric tumors contributes to early detection, diagnosis and treatment. It may improve long-term survival outcomes in LT recipients.

Objective To investigate the risk factors of pancreatic pseudocysts(PPC) in patients with acute pancreatitis (AP) in a retrospective cohort study. Methods 460 AP patients with complete follow-up data admitted in Affiliated Hospital of Qingdao University from January 2004 to March 2012 were retrospectively analyzed,who were divided into PPC group and control group. Age,gender,body mass index(BMI),history of diabetes,etiology,the presence of ascites and hydrothorax,the presence of abdominal mass,the presence of acute fluid collection, APACHEⅡ score at 48 h admission, CT severity index (CTSI), serum albumin, amylase,LDH,ALP, BUN, Cr, TG, TB, conjugated bilirubin, CRP, serum calcium and other laboratory markers were recorded. Univariate logistic regression analysis was used to select the factors that were statistically different between two groups, and multivariate logistic regression analysis was performed to determine the independent risk factors for AP complicated with PPC. Results 143(31.1%) of 460 AP patients developed PPC. On univariate analysis, a total of 11 factors including male sex, BMI ≥28 kg/m2, history of diabetes, alcoholic pancreatitis, ascites, pleural effusion, palpable abdominal mass, acute fluid collections,APACHEⅡscore,CTSI≥7 and serum albumin were statistically different between two groups. On multiple logistic regression analysis, it was shown that male sex (OR 3.23, 95% CI 1.560~ 6.301, P=0.03),history of diabetes (OR 2.23,95% CI 1.021~3.920,P=0.04), ascites (OR 1.62,95% CI 0.652~2.432, P=0.01), pleural effusion (OR 2.43, 95% CI 1.201~7.201, P=0.03), a palpable abdominal mass(OR 1.83,95% CI 0.737~4.320,P<0.001) and CTSI≥7(OR 5.12,95% CI 1.890~14.012, P<0.001) were independent risk factors significantly associated with the PPC formation. Conclusions The male sex, diabetic history, ascites, pleural effusion, palpable abdominal mass and high CTSI score were the independent risk factors of PPC formation in AP.

Objective To explore the risk factors,the distribution of etiology and drug resistance status of patients with early infection (3 months) after liver transplantation,and to provide reference for clinical diagnosis and treatment.Methods The clinical data of 112 recipients from February 2014 to December 2015 were collected,and logistic regression analysis was performed on the risk factors of early postoperative infection in liver transplant patients.The independent risk factors of infection after liver transplantation were screened out.At the same time,the results of pathogen culture and drug sensitivity test were statistically described.Results The independent risk factors for infection at 3th month after liver transplantation included the operative time ≥600 min [P =0.003,odds ratio (OR) =9.996,95 ％ confidence interval (95 ％ CI),2.221-44.981],intensive care unit (ICU) ≥6 days (P =0.010,OR =6.306,95％ CI =1.563-25.437),Child-Pugh grade of C (P =0.023,OR =6.298,95％ CI =1.294-30.659).Of the 112 liver transplant recipients,59 had an infection (52.68％),and 168 stains of pathogens were isolated.The positive rate of the specimens was highest in sputum,followed by bile,ascites,drainage and catheter end,blood,deep vein catheter,middle urinary,pleural effusion and peripherally inserted central catheter (PICC).The detectable rate of gram-negative bacteria,gram-positive bacteria,fungi and viruses was 46.43％ (78 strains),29.76％ (50 strains),18.45％ (31 strains),and 5.36％ (9 strains) respectively.Infection occurred mainly within 1 month after surgery,accounting for about 80.36％ (135 strains),especially at 1st week after surgery,accounting for about 34.52％ (58 strains).Gram-positive bacteria had a higher drug resistance rate,including penicillins,macrolides,aminoglycosides,quinolones,linamides,etc.especially in the highest rate of Enterococcus faeciurr.Gram-negative bacteria were individualized based on the different strains of the bacteria,and they were relatively low in the resistance of the carbapene.Conclusion Infection is one of the most common complications after liver transplantation.To reduce the incidence of infection after liver transplantation,efforts should be made to shorten the duration of operation and ICU stay time,improve the basic nutritional status of recipients,and enhance monitoring of the recipient's infection after liver transplantation,to further increase the survival rate of postoperative liver transplantation recipients and improve the quality of life.

Objective To detect serum biomarkers for pancreatic cancer associated diabetes and establish a model for diagnosis.Methods SELDI-TOF-MS was used to detect the differentially expressed serum proteins from 17 pancreatic cancer associated diabetes patients,17 new-onset type Ⅱ diabetes patients and 17 healthy controls,then a model of biomarkers was constructed and validated by Biomarker Patterns Software 5.0.Results Twelve discriminating m/z peaks were identified in the protein fingerprints in 10 pancreatic cancer associated diabetes patients,10 new-onset type Ⅱ diabetes patients and 10 healthy controls.Among them,the three biomarkers of mass/charge ratio 6116,6695 and 8936 were used to construct the model,which could diagnose 90％ pancreatic cancer associated diabetes form control groups.Blind test of other7 samples of three groups showed that 100％ pancreatic cancer associated diabetes,71％ new-onset diabetes and 86％ healthy controls were correctly classified.After searching protein database,there were metallothionein,pancreatic progenitor cell differentiation and proliferation factor-like protein,and fibroblastic growth factor 1,which were close to the weights of the above mentioned 3 differentially expressed proteins.Conclusions SELDI can identify 3 biomarkers for pancreatic cancer associated diabetes and a reliable model for diagnosis of pancreatic cancer associated diabetes is established.

Objective To investigate the apoptosis-inducing effect and anti-proliferative effect of epigallocatechin-3-gallate (EGCG) on human pancreatic cancer cell SW1990 in vitro. Methods The effect of proliferation was evaluated by MTT after the SW1990 cells in vitro were incubated with different concentrations of EGCG (6.25, 12.5, 25, 50, 100 μg/ml). The apoptosis-inducing effect was determined by flow cytometry after the cells were treated with 25 μg/ml of EGCG. The cell cycle of SW1990 cells was detected by flow cytometry after the cells incubated with different concentrations of EGCG (0, 10, 20, 30, 40, 50 μg/ml).Results After SW1990 cell were treated with different concentrations of EGCG (0, 25, 50 μg/ml), the values of A492 were 0.46 ±0.04,0.42 ±0.04,0.27 ±0.03 at 24 h; 0.48 ±0.02, 0.31 ±0.03,0.16 ±0.02at 48 h; 0.51 ±0.01,0.24 ±0.04,0. 14 ±0.04 at 72 h. EGCG inhibited the proliferation of SW1990 in a doseand time-dependant manner(P ＜0.01 ). The apoptotic rates at 24, 48, 72 h were (8.33 ± 1.15 )%, (19.77 ±0.81 )%, (29.17 ± 0.75 )% in the EGCG treatment group; while the corresponding values were (2.77 ±0.45 ) %, (3.20 ± 0.26 ) %, (3.67 ± 0.35 ) % in the control group; and the difference was statistically significant (P ＜0.01 ). After 0, 20, 50 μg/ml of EGCG treatment for 24 h, the percentages of SW1990 cellsin G0/G1 stage were (57.59 ±0.97)%, (62.99 ± 1.91 )%, (68.87 ± 1.88)%, and the percentages of SW1990 cells in G0/G1 stage increased with the increase of concentrations of EGCG, while the percentages of SW1990 cells in G2/M stage decreased with the increase of concentrations of EGCG (P ＜0.01 ). Conclusions EGCG can significantly inhibit the proliferation of SW1990 cells. The mechanism may be related to the apoptosis-inducing effect and the regulation of the cell cycle of the SW1990 cells.