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 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 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 retrospectively analyze the clinical characteristics and treatment of patients with facial onset sensory and motor neuronopathy (FOSMN).Methods　FOSMN syndrome were searched in PubMed,EMbase,CBM,CNKI,WanFang Data database,from the date of database establishment to 2019,and combined with a case admitted to our hospital.The clinical characteristics and treatment were analyzed from above data.Results　A total of 27 studies were included,42 males and 25 females,with an average onset age of (51.0±12.4) years.Clinical features:85.1% had numbness in the face or mouth as the initial symptom,53.7% had facial muscle weakness,56.7% had facial muscle atrophy,50.7% had abnormal corneal reflex,more than 80% had bulbar syndrome,and more than 50% had neck flexion or upper limbs weakness,47.8% had neck or upper limb muscle atrophy,and 43.3% had tongue muscle atrophy.Pathological examination of autopsy or muscle biopsy showed loss of involvement nucleus and spinal cord neurons,as well as muscle neurogenic atrophy.TDP-43-positive inclusions were found by autopsy.Neuroelectrophysiological examination:83.6% had prolonged or disappeared blink reflex,88.1% had acute or chronic progressive denervation,and 55.2% had lower SNAP amplitude in upper limbs.Treatment:Of the,1/30 cases had a clear improvement with IVIg therapy.Some patients continued to progress after IVIG,glucocorticoids,and plasma exchange therapy;16 patients were died with an average duration of 7.7 years.Conclusion　FOSMN syndrome begins with abnormal sensory in the trigeminal nerve distribution area.The lesions spread from top to bottom in the brainstem,gradually involving the motor nucleus in bulbar,and spinal cord anterior horn.The abnormal blink reflexes,neurogenic damage,and SNAPs amplitude reduction in neuroelectrophysiological examinations have diagnostic value.There is a high possibility of degenerative diseases and no effective treatment for the disease currently.

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.

Objective To study the predictive value of magnetic resonance imaging (MRI),positron emission computed tomography (PET)and PET/MRI coregistration in intractable epilepsy of children.Methods A retrospec-tively analysis was performed based on the surgery data at the Department of Children Epilepsy Center of Peking Univer-sity First Hospital from September 2015 to March 2016.The clinical data,surgery and follow－up study data,interictal and ictal electroencephalogram,MRI,PET and PET/MRI coregistration data were collected.By comparison with the epi-leptogenic zone designed by pre－surgical workup,the accuracy of MRI,PET and PET/MRI coregistration in detecting lesion was assessed.In the patients who had no seizure during≥1 year follow－up,their sensitivity,specificity,positive predictive value,negative predictive value of MRI,PET and PET/MRI coregistration were calculated.Results (1)A total of 62 patients underwent surgery,30 boys and 32 girls. The average age on epilepsy onset was 2. 50 years (2 days－11.70 years),and average age on surgery was 5.10 years old(0.75－15.60 years old).(2)Surgical treat-ment of 62 cases included the resection of the focal or lobar (32 cases,51.6%),and the multilobar (16 cases, 25. 8%).Hemispherotomy was done in 14 cases (22.6%).During ≥1 year follow－up,seizure outcome was Engel class Ⅰ in 57 cases (91.9%)out of the 62 patients,Engel classⅡto Engel classⅣin 1 case,3 cases,and 1 case, respectively.(3)Referred to epileptogenic zone designed by presurgical workup,MRI represented 64.5%(40/62 ca-ses)results with accordance,PET and PET/MRI coregistration was 72.5%(45/62 cases)and 85.5%(53/62 cases), respectively,and the difference was significant(χ2＝7.25,P＝0.03).(4)Based on the patients of Engel class Ⅰ, their sensitivity and specificity were 66.7%,60.0% in MRI,75.4%,60.0% in PET %,and 85.9%,80.0% in PET/MRI coregistration,respectively.(5)There were 11 ＂non－lesion＂ cases of all focal cortical dysplasia in patholo-gy,and subtle structural abnormalities were de tected in 9 cases by reviewing MRI.Conclusions PET/MRI coregistra-tion can improve lesion detection of intractable epilepsy in children.

Objective To investigate the diagnostic value of diffusion kurtosis imaging(DKI)in the classification of hepatic fibrosis. Methods Thirty-five male SD rats were randomly divided into two groups:the hepatic fibrosis group(n=28)and the control group(n=7). The rats in hepatic fibrosis group were randomly divided into 4 subgroups and seven rats per group, the rats were administrated 50％ CCl4 intraperitoneally twice a week to establish hepatic fibrosis , and the four subgroups were injected 2, 4, 6, and 8 weeks, respectively. The rats in the control group were administrated same dose of olive oil for 8 weeks. One rat in hepatic fibrosis group was died of liver failure in the 7th week, and a total of 27 fibrosis experimental rats and 7 control rats were finally included in this study. DKI was performed at the end of the injection period for all rats, the apparent diffusion(D)and kurtosis(K)values were evaluated. Rats were sacrificed immediately after MRI scan and liver specimens were collected. The liver tissues were examined by pathology, liver fibrosis degree, which was graded from S0 to S4, and inflammatory activity, which was graded from G0 to G3 were graded. The difference of D value and K value between different liver fibrosis and inflammatory activity scores was compared by one-way ANOVA(normal distribution)or Kruskal-Wallis test(skewed distribution). Spearman correlation analysis and multiple regression analysis were used to reveal the correlation between DKI parameters and fibrosis staging/necroinflammatory activity grade. To confirm the efficiency of using the ROC curve of DKI parameters to qualify the liver fibrosis grade, which grade was≥3. Results Seven, 6, 6, 7, 8 rats were diagnosed as S0 to S4, respectively. The difference of D value and K value among different fibrosis grades was statistically significant(P<0.05). D value and the degree of fibrosis was negatively correlated(r=-0.650, P<0.01);K value and liver fibrosis grade no correlation(r=0.336, P=0.080). Thirteen, 6, 8, 7 rats were diagnosed as G0 to G3, respectively. D value was negatively correlated with inflammatory activity(r=-0.590, P=0.001);K value was no correlation with inflammatory activity(r=0.169, P=0.389). Compared with inflammatory activity, fibrosis classification was an independent factor in determining D values(P=0.001). ROC analyses demonstrated an area under the curve(AUC)of D value, K value, D value combined with K value in the diagnosis of liver fibrosis grading ≥ 3 level were 0.781, 0.672 and 0.833, respectlively. The sensitivity and specificity of D value combined with K value were 83.3％ and 75.0％, respectively. Conclusion DKI imaging is of great value in the classification of hepatic fibrosis and can be used as an effective method for the diagnosis of fibrosis.

Objective To explore the factors related with neurological function in children after hemispherectomy for intractable epilep-sy. Methods Thirty-three children suffered hemispherectomy from May, 2014 to June, 2015 were analyzed. Their preoperative data were col-lected. A structured questionnaire was used to evaluate the neurological function. The relationship between preoperative parameters and post-operative functional outcomes was analyzed. Results Bilateral lesions in MRI (P<0.001) and age (P<0.001) were related with functional out-come. Conclusion The prognosis of hemispherectomy for children with intractable epilepsy is related to the contralateral lesion and age.

Aim To introduce and apply artificial lumbar interverte-brai disc replacement for the treatment of lumbar disc degenerative diseasesand lumbar disc herniation accompanying evident disc space narrowing andinvestigate the regulation of its recovering spinal motion and carrying a-bility. Methods Thirty-one cases (37 discs) of artificial lumbar disc re-placement were performed using SB Charite Ⅲ from April 1998 to April2000. Among them, disc degenerative diseases were in 16 cases (18discs), disc herniation accompanying evident disc space narrowing in 13cases ( 17 discs), rec urrent dise herniation in 2 cases. The rehabilitationtraining was done under postoperative instructions. Results All the caseswere followed up from 17 to 41 months (averagely 26 months) untilSeptember 2001. The clinical outcomes were excellent in 23 cases, goodin 6 cases, fair in 2 cases. The mobility of the operated level had 4.0°anterior flexion and 5. 1° posterior extension after operation and 9.1° ontotal mobility. Meanwhile, the operated intervertebral space got an average4. 2 mm higher than that before. Because of technical problem, a slightdisplacement of the core occurred in one case without any clinical symp-toms and signs. Conclusion Artificial lumbar disc replacement can re-covery spinal motion and carrying capacity and provides a new kind ofoperation for the treatment of lumbar disc degenerative diseases and discherniation accompanying evident disc space narrowing.