Intestinal organoids are constructed by crypts or stem cells from the intestine under the 3D support of the culture matrix. They contain all mature cells of the intestine, and have become a new and efficient platform for studying the mechanism of intestinal diseases. Compared with 2D cell culture, organoids can not only more effectively simulate the physiological structure and function of the intestine, but also better restore the true ecology of the intestine in different external environments. Therefore, it is more widely used in the study of pathogenesis of different intestinal diseases. This article reviewed the new progress of intestinal organoids culture, and the application and progress of intestinal organoids in the pathogenesis of inflammatory bowel diseases, colorectal cancer and celiac disease in recent years, and also discussed the application of intestinal organoids in drug research and development and screening.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.
Child ; Aged ; Adolescent ; Middle Aged ; Humans ; Female ; Hypertension, Pulmonary/therapy* ; Retrospective Studies ; China/epidemiology* ; Familial Primary Pulmonary Hypertension ; Pulmonary Arterial Hypertension/complications* ; Heart Defects, Congenital

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.
Child ; Aged ; Adolescent ; Middle Aged ; Humans ; Female ; Hypertension, Pulmonary/therapy* ; Retrospective Studies ; China/epidemiology* ; Familial Primary Pulmonary Hypertension ; Pulmonary Arterial Hypertension/complications* ; Heart Defects, Congenital

Objective: A permanent stoma can seriously affect patients' quality of life. Clinicians need to consider the risk of a permanent stoma when making clinical decisions. This study analyzed preoperative predictors of a permanent stoma after laparoscopic intersphincteric resection for low rectal cancer (LISR), and a prediction model was constructed validated. Methods: This was a retrospective study that analyzed clinical data of 331 ultralow rectal cancer patients who were diagnosed with primary rectal adenocarcinoma by endoscopy and pathology, including 218 males and 113 female, (58.8±11.2) years and (23.7±3.1) kg/m². The patients underwent LISR with a preventive stoma from January 2012 to December 2020. Patients with multiple primary colorectal cancers, who underwent emergency surgery for intestinal obstruction or bleeding or perforation, and did not complete 18 months follow up were exclucled. R software was used to randomly select 234 patients as the modeling group with a ratio of approximately 7:3, and the remaining 97 patients comprised the validation group. The stoma site was determined by the surgeon before the operation, and the ileum 30 cm from the ileocecal valve was selected. The rates of a permanent stoma for the entire group and the preoperative clinical factors that may affect the permanency of a stoma in the modeling group were determined. A permanent stoma was defined as failure to close the stoma at 18 months after surgery. Multivariate logistic regression analysis was used to analyze the preoperative independent risk factors for a permanent stoma after LISR. R software was used to create the nomogram model, and the predictive ability of the nomogram model was evaluated by receiver operating characteristic (ROC) curve analysis. Results: Among the 331 patients who underwent LISR, 37 (26 cases in the modeling group and 11 cases in the validation group, 11.2%) developed a permanent stoma for the following reasons: anastomotic stenosis due to leakage (16 cases, 43.2%), distant metastasis (16 cases, 43.2%), intolerant to stoma closure surgery (3 cases, 8.1%), stenosis due to postoperative radiation (1 case, 2.7%), and poor recovery of anorectal function (1 case, 2.7%). Univariate analysis showed that preoperative neoadjuvant chemoradiotherapy, poorly differentiated tumor, cT3 stage, and distant metastasis were associated with a permanent stoma. Multivariate logistic regression analysis showed that neoadjuvant chemoradiotherapy [OR=3.078, 95% confidence interval (CI): 1.326-7.147; P=0.009], cT3 stage (OR=2.257, 95%CI: 1.001-5.091; P=0.049), and stage IV cancer (OR=16.180, 95%CI: 2.753-95.102; P=0.002) were independent risk factors for permanent stoma after LISR. Based on the selected risk factors, a nomogram model for predicting permanent stoma was constructed. The area under the ROC curve of the modeling group was 0.793, the optimal cut-off value was 0.890, the sensitivity was 0.577, and the specificity was 0.885. The area under the ROC curve of the validation group was 0.953. The corrected curves of the modeling group and the validation group showed a good degree of fit. Conclusion: Neoadjuvant chemoradiotherapy, cT3 stage, and distant metastasis are independent predictors of a permanent stoma after LISR, and the nomogram model is helpful to predict the probability of a permanent stoma. Patients with high-risk factors should be adequately informed of the risk of a permanent stoma before colorectal surgery.
Female ; Humans ; Male ; Constriction, Pathologic/etiology* ; Laparoscopy/adverse effects* ; Nomograms ; Quality of Life ; Rectal Neoplasms/pathology* ; Retrospective Studies ; Risk Factors

In this study, UPLC-Q-Exactive-MS/MS was used to rapidly analyze the chemical constituents of Meconopsis quintupli-nervia, and the anti-liver fibrosis mechanism of M. quintuplinervia was preliminarily analyzed by network pharmacology, molecular docking, and cell experiments. The chemical constituents of M. quintuplinervia were identified according to the information of MS~1 and MS~2, as well as the data in the literature and databases. SwissTargetPrediction and TargetNet were used to predict the potential targets. The targets related to liver fibrosis were collected from GeneCards and OMIM. The protein-protein interaction(PPI) network was constructed by STRING. Cytoscape 3.6.1 was used to construct and analyze the "constituent-target-disease" network to obtain key targets and their corresponding constituents in the network. DAVID 6.8 was used for GO analysis and KEGG signaling pathway enrichment analysis. Finally, the preliminary verification was carried out by molecular docking and cell experiments. As a result, 106 chemical constituents were identified from M. quintuplinervia, including 66 flavonoids, 16 alkaloids, 18 phenolic acids, 1 anthocyanin, and 5 other constituents. Among them, 3 constituents were identified as potential new compounds, and 59 constituents were reported in M. quintuplinervia for the first time. Network pharmacology analysis showed that M. quintuplinervia presumably acted on AKT1, SRC, JUN, EGFR, STAT3, HSP90 AA1, MAPK3, and other core targets through luteolin, isorhamnetin, quercetin, apigenin, kaempferide, amurine, 2-methylflavinantine, allocryptopine, the multi and other active compounds, thereby regulating the PI3 K/AKT signaling pathway, pathways in cancer, proteoglycans in cancer, FoxO signaling pathway, and other pathways to exert anti-liver fibrosis effects. M. quintuplinervia extract(MQE) could significantly down-regulate PI3 K and AKT protein levels in the HSC-T6 cell model induced by TGF-β1, suggesting that MQE may have the ability to regulate the PI3 K/AKT signaling pathway. The findings of this study indicated that the anti-liver fibrosis effect of M. quintuplinervia had multi-constituent, multi-target, and multi-pathway characteristics, which may provide a scientific basis for the research on the pharmacodynamic materials, action mechanism, and quality markers of M. quintupli-nervia.
Tandem Mass Spectrometry ; Molecular Docking Simulation ; Network Pharmacology ; Proto-Oncogene Proteins c-akt ; Papaveraceae ; Liver Cirrhosis ; Drugs, Chinese Herbal/pharmacology*

To target neovasculature and tumor cells, a novel cationic liposome with verteporfin (BPD) active-loaded in lumen (CLL) was designed and its basic in vitro and in vivo behaviors were evaluated in this study. Calcium acetate gradient loading method was applied to encapsulate BPD actively and cationic lipid (2,3-dioleoy-loxy-propyl)-trimethylammonium (DOTAP) was added by post-insertion for the positive charge of CLL. Results of characterization showed that the diameter and zeta-potential of CLL were around 100 nm and 28 mV, respectively. Compared with passive loading liposomes, CLL significantly enhanced the stability of BPD loading. What's more, the loaded BPD in lumen could switch off the fluorescence and photosensitization during blood circulation by homo-fluorescence resonance energy transfer (homo-FRET) effect, leading to the diminished phototoxicity to normal tissues. In vitro cellular uptake and cytotoxicity assay exhibited that positive charge dramatically enhanced the uptake of CLL both in vascular endothelial cells and tumor cells leading to superior therapeutic efficacy. In vivo study further showed that CLL reduced the clearance rate and increased tumor accumulation compared with passive loading group. Quantitative results of exvivo organ indicated that negligible CLL distributed in normal organs contributing to low phototoxicity. Animal experiments were conducted according to the Guidelines of the Experimental Animal Ethics Committee of Peking University Health Science Center and International Animal Experiments. In conclusion, we successfully designed a novel cationic targeting liposome that overcame the limitations of passive loading and significantly enhanced the efficacy of photodynamic therapy.

Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg^-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg^-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg^-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.