The most effective treatment for end-stage liver disease (ESLD) in children is liver transplantation (LT ). After LT, recipients must take immunosuppressants for a long time to maintain graft function. The side effects of immunosuppressants affect long-term recipient survival. Many domestic and global centers have made great efforts to taper or completely remove immunosuppressants in recipients in recent years. Some recipients successfully achieve immune tolerance after withdrawing immunosuppressants. However, there are no definite and effective protocols or indicators for immunization evaluation. And few studies focused upon the safety and long-term outcomes of immunosuppressant withdrawal. This review discussed the protocols and researches of immune tolerance after pediatric LT to provide practical guidance for a withdrawal of immunosuppressants and clinical advice of immune tolerance.

Organoid is a newly developed cellular there-dimensional culture system in recent years. Organoids have a three-dimensional structure, which is similar to that of the real organs. Together with the characteristics of self-renewal and reproduction of tissue origin, organoids can better simulate the function of real organs. Organoids provide a new platform for the study of organogenesis, regeneration, disease pathogenesis, and drug screening. The digestive system is an essential part of the human body and performs important functions. To date, organoid models of various digestive organs have been successfully established. This review summarizes the latest research progress of organoids of taste buds, esophagi, stomachs, livers and intestines, and prospects future application of organoids.
Humans ; Organoids ; Intestines ; Liver

Objective:To investigate the difference of 24h urinary metabolic abnormalities in patients with different subtypes of calcium oxalate stones.Methods:The clinical data of 120 patients with simple calcium oxalate stones admitted to the Second Affiliated Hospital of Zhengzhou University from March 2018 to May 2020 were retrospectively analyzed.There were 90 males (75.0%) and 30 females (25.0%), with the age of (49.1 ±13.5) years old, and body mass index (BMI) of (24.6 ±3.0) kg/m 2. There were 23 cases of diabetes mellitus (19.2%), 8 cases of coronary heart disease (7.0%), 36 cases of hypertension (30.0%) and 45 cases of gastrointestinal diseases (37.5%). There were 11 cases (9.2%) of low pH, 54 cases (45.0%) of hyperoxaluria, 19 cases (15.8%) of hypercalcemia, 72 cases (60.0%) of hypocitrouria, 3 cases (2.5%) of hyperuricuria, and 18 cases (15.0%) of hyperuricemia. In the 120 patients, 79 underwent ureteral soft lithotripsy, 28 underwent percutaneous nephrolithotomy, and 13 underwent extracorporeal shock wave lithotripsy. The patients were divided into calcium oxalate monohydrate stone group (COM group) and calcium oxalate dihydrate stone group (COD group). The general clinical data and urinary metabolic data of the two groups were compared. Independent risk factors for stone formation of the two groups were analyzed. Results:There were 120 cases in this study, with 90 cases in COM group and 30 cases in COD group. Urinary oxalic acid in COM group and COD group was 41.3 (30.1, 54.2) mg and 34.1 (26.6, 39.9) mg, respectively, and the difference was statistically significant ( P=0.01). The incidence of hyperoxaluria was 52.2% (47 cases) and 23.3% (7 cases), respectively, and the difference was statistically significant ( P<0.01). Urinary calcium in COD group and COM group was 6.8 (6.1, 8.8) mmol and 4.0 (2.3, 5.2) mmol, respectively, and the difference was statistically significant ( P<0.01). The incidence of hypercalcemia was 43.3% (13 cases) and 6.7% (6 cases), respectively, the difference was statistically significant ( P<0.01). The urinary phosphate in COM group and COD group was 2 063.5 (1 688.8, 2 803.2) mg and 1 231.7 (766.7, 1 740.9) mg, respectively, and the difference was statistically significant ( P<0.01). The serum uric acid level in COM group and COD group was (343.0±111.7)μmol/L and (297.6±77.6)μmol/L, respectively, and the difference was statistically significant ( P<0.05). There were no significant differences in term of age, gender, body mass index, diabetes mellitus, coronary heart disease, hypertension, gastrointestinal disease, parathyroid hormone (PTH), hemoglobin, serum creatinine, serum potassium, serum phosphorus, serum calcium, serum sodium, stone load and side between the two groups ( P>0.05). There were no significant differences in urinary sodium, urinary phosphorus, urinary magnesium, urinary citric acid and urinary uric acid levels between the two groups ( P>0.05). Binary Logistic regression analysis showed that hyperoxaluria was an independent risk factor for COM patients ( OR=4.859, P<0.01). Increased urinary phosphoric acid level was an independent risk factor for COM patients ( OR=1.001, P<0.01). Hypercalcemia was an independent risk factor for COD patients ( OR=27.856, P<0.01). Conclusions:COM calculus patients have higher urinary oxalic acid and urinary phosphoric acid levels, and are more likely to have hyperoxaluria. COD calculus patients have higher urinary calcium levels and are more likely to develop hypercalcemia.

Objective:To explore the predictive value of psoas muscle index(PMI)on early survival and complications after liver transplantation(LT)in children with biliary atresia(BA).Methods:Between January 1, 2016 and September 30, 2020, the relevant clinical data are retrospectively reviewed for 244 BA children undergoing LT at Department of Pediatric Liver Transplantation, Tianjin First Central Hospital.Total psoas muscle area(PMA)at the level of the third lumbar endplate is measured based upon preoperative abdominal computed tomography(CT)and normalized by the square of length for obtaining the value of PMI.According to the survival at Year 1 post-LT, receiver operating characteristic(ROC)curve is plotted and the cut-off value calculated.According to the cut-off value, they are divided into two groups of high PMI(173 cases)and low PMI(71 cases). Then the clinical data of 2 groups are compared.Kaplan-Meier survival curves at Year 1 post-LT are analyzed.And Cox proportional hazard model is utilized for conducting a multivariate analysis of early death.Results:The cut-off value of PMI is 534.6 mm 2/m 2.Two groups are compared in terms of age, gender, weight-for-age Z-score(WAZ), length-for-age Z-score(LAZ)and preoperative laboratory parameters ( P>0.05). Significant inter-group differences existed in the types of donors and surgery( P<0.05), and the median age of recipients in low PMI is higher than high PMI group(7.77months vs 6.57 months, P<0.01). The proportion of children with a history of Kasai surgery in low PMI group(78.87% vs 53.76%, P<0.01)and the median length of stay in hospital(23 d vs 20 d, P=0.03)is higher in low PMI group, but recipients(88.7% vs 97.1%, P<0.01)and grafts(87.3% vs 96%, P=0.01)1-year survival rate are lower.Multivariate analysis indicated that high PMI is a protective factor for early postoperative survival( HR=0.132, 95% CI: 0.028~0.626, P=0.011). Conclusions:PMI is an independent predictor of early survival post-LT and has a certain predictive value for early graft loss in BA children.

Objective:To study the impact of donor left hepatic vein classification and the reconstruction methods on hepatic venous outflow obstruction (HVOO) after pediatric living-donor liver transplantation using left lateral liver segments.Methods:A retrospective study was performed on the clinical data of 653 children recipients who underwent living-donor liver transplantation with left lateral liver segments from January 2014 to December 2020 at Tianjin First Central Hospital. There were 309 males and 344 females, aged 7.0 (6.0, 10.0) months, with an age range of 3-121 months. Based on the left hepatic vein on preoperative donor enhancement CT as well as the intraoperative reconstruction methods, the recipients were divided into 3 groups: type Ⅰ group ( n=514), anastomosis using a single opening was performed directly between the donor and the recipient; type Ⅱ group ( n=118), angioplasty was performed on two adjacent recipient venous orifices before anastomosis, and type Ⅲ group ( n=21), an interposition vessel was anastomosed to two widely spaced openings or the two veins were anastomosed separately. The preoperative general status of the patient, postoperative HVOO incidences, and graft and recipient survival rates were compared among the three groups. The patients were followed up by outpatient reexamination or telephone. Results:Graft to recipient weight ratio in the type Ⅲ group was smaller than that in the type Ⅰ group and the type Ⅱ group ( P<0.05). For all the 653 patients, the incidence of postoperative HVOO was 4.59% (30/653), with the incidences of HVOO in the 3 groups of patients were 4.1% for the type Ⅰ group (21/514), 5.1% for the type Ⅱ group (6/118), and 14.3% for the type Ⅲ group (3/21), respectively. There was no significant difference among the groups ( P>0.05). The recipient cumulative survival rates at 1 and 3 years after surgery in the type I group were 97.8% and 97.0%, and the corresponding rates in the type Ⅱ group were 96.5% and 94.2%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. There was a significant difference between the type Ⅰ and type Ⅲ groups ( P=0.048). The graft cumulative survival rates at 1 and 3 years in the type Ⅰ group were 97.4% and 96.9%, and the corresponding rates in the type Ⅱ group were 94.9% and 92.5%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. The difference in the postoperative graft cumulative survival rates between the type Ⅰ group and type Ⅱ group was significant ( P=0.044). Conclusions:The anatomy of the left hepatic vein supplying the left lateral liver segment was highly variable, and the majority of the variations could be reconstructed. A reasonable reconstructive method could reduce the incidence of postoperative HVOO and improved the outcomes of the graft.

Objective:To investigate the pathogenic bacteria profiles in preoperative urine bacterial cultures of patients with infected kidney stones and use antibacterial drugs to prevent recurrence.Methods:The data of 79 cases with infected kidney stones admitted to the Second Affiliated Hospital of Zhengzhou University from January 2017 to July 2021 were retrospectively analyzed, among whom 29 (36.7%) were male and 50 (63.3%) were female. The age ranged from 17-75 years, with a median age of 49.0 (40, 55) years. Fifteen cases (19.0%) combined hypertension, 13 cases (16.5%) combined diabetes mellitus, and 3 cases (3.8%) combined with cardiovascular disease. Fifty-one cases (64.6%) were diagnosed with cast infectious stones. All patients underwent surgical lithotripsy, and postoperative review of the urological computerized tomography (CT) revealed no residual stones defined as complete lithotripsy, and postoperative oral medication was continued to control infection and prevent stone recurrence. According to post-hospitalization compliance, patients were divided into high and low compliance groups. The high compliance group consisted of patients who returned to the hospital regularly for routine urinalysis and urine bacterial culture after discharge, followed the doctor's prescription for standardized antibacterial drug therapy, and complied with urease inhibitor therapy for ≥6 months. The low compliance group included patients who did not take sensitive antimicrobial drugs regularly and/or were unable to adhere to the medication even after the reduction of vinblastine due to adverse events such as tremor, palpitations, headache, anemia, or gastrointestinal discomfort. The recurrence of stones at 3, 6 and 12 months of follow-up was compared between the two groups.Results:Of the 79 cases in this group, 56(70.9%) were completely clear of stone after surgery. Thirty-three cases (41.8%) presented positive in preoperative urine bacterial culture, and the most common causative organism was Aspergillus oddus in 17 cases (21.5%), followed by Escherichia coli in 8 cases (10.1%) and Klebsiella pneumoniae in 3 cases (3.8%). Among the 17 positive cases of A. oddis, six were positive for ultra broad spectrum β-lactamases (ESBLs), 6/6 were resistant to ampicillin, cefazolin, and cotrimoxazole, 1/6 were resistant to amikacin, cefoxitin, and ticarcillin/stick acid, and none were resistant to imipenem, polymyxin, or aminotrans (0/6 cases). Of the cases, 11 were negative for ESBLs. Ten out of eleven cases were resistant to ampicillin. Furthermore, 8/11 cases were resistant to cefazolin, levofloxacin, ciprofloxacin, and cotrimoxazole and 1/11 were resistant to cefoxitin, cefaclor, furantoin, amikacin, and minocycline, and 0/11 were resistant to imipenem, ticarcillin/stick acid, aminotrans. ESBLs positive strains were resistant to 78.6% of the tested drugs (cefaclor, cefazolin, ceftazidime, furantoin, norfloxacin, levofloxacin, ciprofloxacin, cefoxitin, amoxicillin/rod acid, ticarcillin/rod acid, ampicillin, ceftriaxone, cefotaxime, cefuroxime, cefepime, gentamicin, cotrimoxazole, tobramycin, amikacin, tetracycline, chloramphenicol, and minocycline) at a lower rate of resistance than ESBLs positive strains. Of the eight positive cases of E. coli, seven were ESBLs positive, 7/7 were resistant to ampicillin, cefazolin, cefotaxime, cefuroxime, and cefepime, 1/7 were resistant to cefoxitin and minocycline, and 0/7 were resistant to imipenem, furantoin, or amikacin. One case was ESBLs negative and was resistant to all antimicrobial drugs except for ampicillin. Stone recurrence rates at 3, 6, and 12 months after discharge were 9.1%(4/44) and 31.4%(11/35), 13.6%(6/44), respectively, in the high compliance group, and 60.0%(21/35), 36.4%(16/44), and 71.4% (25/35), respectively, in the low compliance group. All differences were statistically significant.Conclusion:The most common pathogenic bacteria isolated from urine bacterial cultures of patients with infectious stones were A. chimaera, E. coli, and K. pneumoniae. The resistance rate of ESBLs-positive strains to antimicrobial drugs was significantly higher than that of ESBL-negative strains, and the resistance rate of antimicrobial drugs such as β-lactamase inhibitors, cefoxitin, amikacin, and imipenem was low. Combination therapy with standardized sensitive antimicrobial drugs and urease inhibitors significantly reduced the recurrence rate of stones among patients.

Objective To investigate the effect of short-term complications after D2 radical gastrectomy on long-term survival rate of gastric cancer patients. Methods A retrospective case-control study was conducted on 421 patients with gastric cancer who underwent D2 radical gastrectomy. According to the short-term postoperative complications, they were divided into experimental group (complication group, n=76) and control group (without complication group, n=345). In order to reduce the selection bias, the long-term survival rate of the two groups was tested by Kaplan-Meier survival analysis method after balancing the variables by propensity score matching (PSM). Log rank method was used for univariate analysis and Cox multivariate analysis was used for prognostic factors. Results There was no significant difference in long-term survival rate between the experimental group and the control group (P > 0.05). Histological type, lymph node metastasis rate and pTNM stage were independent risk factors for long-term survival. Conclusion The short-term complications after D2 radical gastrectomy have no significant impact on the long-term survival rate of gastric cancer patients, but it has certain clinical significance to actively prevent and control complications.

Objective:To explore the clinical manifestations and surgical outcomes of pediatric epilepsy patients with epileptic spasms (ES) as the main form of seizure, so as to analyze the correlative factors with prognosis and improve the understanding of the operation and preoperative positioning for such patients.Methods:The clinical data of patients with ES who underwent surgery therapy from June 2014 to December 2015 in Pediatric Epilepsy Center, Peking University First Hospital were collected and retrospectively analyzed.Demographic characteristics, seizure forms, etiology, electroencephalogram (EEG), cranial magnetic resonance imaging (MRI), operative methods, pathological findings as well as surgical outcomes evaluated by Engel classification during follow-up of the subjects were collected.Correlative factors with the prognosis were explored by comparing the data between patients with optimal outcome (Engel Ⅰ) and those with poor outcomes (Engel Ⅱ-Ⅳ).Results:A total of 25 pediatric patients were enrolled, including 16 males (64.0%) and 9 females (36.0%). The age of onset was (0.81±0.68) years, the age at operation was (2.98±1.63) years, and the course of disease was (2.17±1.48) years.Besides, 84.0% (21/25 cases) of the ES patients had multiple forms of seizures and partial seizure (19 cases) was the most common.MRI of the heads of all the children showed definite lesions, including 11 patients (44.0%) with lesions limited to one brain lobe and 14 patients (56.0%) involving multiple brain lobes or hemisphere.The most common etiology was focal cortical dysplasia (13 cases), followed by intracranial developmental tumors (3 cases). All patients underwent resection surgery, including resection of lesion (3 cases), single brain lobe resection (9 cases), multiple brain lobe dissection (3 cases) and hemisphere dissection (10 cases). During a follow-up period of 4.0 to 5.5 years, 1 patient was lost.Among the remaining 24 cases, 18 (75.0%) cases achieved good outcomes and wee classified as EngelⅠ, 2 cases (8.3%) and 4 cases(16.7%) were classified as Engel Ⅱand Ⅳ, respectively.The univariate comparison between the good epilepsy prognosis group and the poor epilepsy prognosis group showed that, patients whose EEG abnormalities are consistent with the anatomical lesions during the inter ictal tend to have good prognosis( P=0.006). Conclusions:(1) Optimal therapeutic effects were observed in ES patients with definite lesions treated by surgical therapy.(2) Interictal EEG consistent with the lesion side may suggest a good prognosis for surgical treatment.(3) Structural causes should be screened as soon as possible if a patient with ES is drug-refractory and presents clues of focal origin.

Objective:To determine any effect of repeated thermal stimulation on the viability and functioning of inflamed human umbilical vein endothelial cells (HUVECs).Methods:Well-cultured HUVECs were divided into a normal group, a model group, a thermal stimulation 5 times group (group A), a thermal stimulation 9 times group (group B) and a thermal stimulation 13 times group (group C) and cultured under the same conditions. The normal group was not given any intervention. The model group was stimulated with 1μg/mL lipopolysaccharide for 1 hour. Groups A, B and C were first subjected to 5, 9 and 13 rounds of repeated thermal stimulation, each round lasting 4 minutes at 43℃ and 1 minute at room temperature. They were then incubated for one hour at 37℃ under a 5% CO 2 atmosphere with 1μg/mL lipopolysaccharide. Cell viability and the expression of NF-κB were evaluated using methyl thiazolyl tetrazolium and immunofluorescence assays. The levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined by enzyme-linked immunosorbent assay. Results:After the intervention, the average cell viability of the model group and of groups A and C was significantly lower than that of the normal group, while that of group B was significantly higher. After the intervention, the average NF-κB expression in the normal group was significantly different from that in the others, with group B′s level significantly different from that of the model group. After the treatment, the average expression of ICAM-1 and VCAM-1 in the model group had increased significantly, while that in groups A, B and C had decreased significantly compared with the normal group. The levels of groups A, B and C were then significantly different from that of the model group. The average ICAM-1 level of group B was significantly different from those of groups A and C.Conclusions:Repeated thermal stimulation can protect inflamed HUVECs and reduce the expression of HUVEC adhesion molecules.

Objective:To investigate the clinical characteristics, surgical methods, complications and prognosis of children younger than 1 year old who had definite epileptogenic lesions under 1 year old.Methods:A total of 14 children with definite epileptogenic lesions and underwent radical surgery in Pediatric Epilepsy Center of Peking University First Hospital from March 2017 to July 2019 were selected.Their clinical data including operation age, course of disease, etiology, physical examinations, seizure types, seizure frequency, features of interictal electrocorticography(EEG), surgical methods, antiepileptic drugs, and pathology were collected and analyzed.Postoperative efficacy was eva-luated using Engel grading.The Griffiths neurodevelopmental scale and the Peabody motor developmental scale were used to assess motor neurodevelopment.Results:The operation age of 14 children was 119 to 358 days (median: 281 days), and the course of disease ranged from 119 to 352 days (median: 266 days). The age of onset was from 0 to 135 days was (median: 7.5 days), and the postoperative follow-up time was 0.5-2.0 years(median: 1.5 years). None of the patients had seizure recurrence at the last follow-up.During the follow-up period, 1 patient had recurrence, but deve-loped no seizures anymore after drug administration.Cognitive and motor functions improved during follow-up in all children.All the children had no serious complications such as postoperative infection and hydrocephalus.Conclusions:Young children with definite epileptogenic lesions have an early onset of seizures, which has a great influence on development.Multidisciplinary preoperative evaluation shows that surgery is a safe way to terminate progression of seizures, thus helping children to well develop and reducing the use of antiepileptic drugs.