Objective To evaluate the effect of Helicobacter pylori(H.pylori)infection on colorectal adenoma(CRA)recurrence after polypectomy and to study other potential prognosis factors associated with CRA recurrence.Methods This single-centered retrospective cohort study included 808 patients with CRA who underwent colonoscopy,polypectomy,and gastroscopy between January 2005 and October 2022.The patients were classified into three groups based on H.pylori infection status:persistently negative(group A,n=626),initially positive but turned negative(group B,n=141),and persistently positive(group C,n=41).The CRA recurrence and high-risk CRA or colorectal cancer(CRC)occurrence were assessed,and potential prognosis factors for recurrence were analyzed.Results During a median follow-up period of 1.6(1.1,2.4)years,the recurrence rate was 56.4%(456/808),including 124 cases(15.3%)of high-risk CRA/CRC[of which 5 cases(0.6%)were CRC]and 332 cases(41.1%)of low-risk CRA.The recurrence rates in the three groups were 55.4%(347/626),60.3%(85/141),and 58.5%(24/41),respectively,with no statistically significant difference(log-rank χ2=0.525,P=0.769).The high-risk CRA/CRC recurrence rates in the three groups were 14.9%(93/626),17.7%(25/141),and 14.6%(6/41),respectively,showing no significant intergroup differences(log-rank χ2=0.340,P=0.844).Multivariate analysis identified increasing age(HR=1.011,95%CI:1.002-1.021,P=0.020)and baseline high-risk CRA(HR=1.428,95%CI:1.183-1.724,P<0.001)as independent prognosis factors for CRA recurrence.Conclusions This study did not find a significant correlation between H.pylori infection and CRA recurrence after polypectomy.Increasing age and baseline high-risk CRA are prognosis factors for CRA recurrence.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective To evaluate the effect of Helicobacter pylori(H.pylori)infection on colorectal adenoma(CRA)recurrence after polypectomy and to study other potential prognosis factors associated with CRA recurrence.Methods This single-centered retrospective cohort study included 808 patients with CRA who underwent colonoscopy,polypectomy,and gastroscopy between January 2005 and October 2022.The patients were classified into three groups based on H.pylori infection status:persistently negative(group A,n=626),initially positive but turned negative(group B,n=141),and persistently positive(group C,n=41).The CRA recurrence and high-risk CRA or colorectal cancer(CRC)occurrence were assessed,and potential prognosis factors for recurrence were analyzed.Results During a median follow-up period of 1.6(1.1,2.4)years,the recurrence rate was 56.4%(456/808),including 124 cases(15.3%)of high-risk CRA/CRC[of which 5 cases(0.6%)were CRC]and 332 cases(41.1%)of low-risk CRA.The recurrence rates in the three groups were 55.4%(347/626),60.3%(85/141),and 58.5%(24/41),respectively,with no statistically significant difference(log-rank χ2=0.525,P=0.769).The high-risk CRA/CRC recurrence rates in the three groups were 14.9%(93/626),17.7%(25/141),and 14.6%(6/41),respectively,showing no significant intergroup differences(log-rank χ2=0.340,P=0.844).Multivariate analysis identified increasing age(HR=1.011,95%CI:1.002-1.021,P=0.020)and baseline high-risk CRA(HR=1.428,95%CI:1.183-1.724,P<0.001)as independent prognosis factors for CRA recurrence.Conclusions This study did not find a significant correlation between H.pylori infection and CRA recurrence after polypectomy.Increasing age and baseline high-risk CRA are prognosis factors for CRA recurrence.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome.METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3,apoptosis-associated speck-like protein containing a CARD (ASC),and caspase-1 precursor (pro-caspase-1) were predicted by molecular docking.Sixty 1-day-old pregnant rats were randomly divided into normal group,model group,dexamethasone group (0.002 g/kg),and Pangshi antai zhixue decoction low-,medium-,and high-dose groups (11.025,22.05,44.10 g/kg),with 10 rats in each group.Each group was given distilled water/corresponding medicinal solution intragastrically,once a day,for 12 consecutive days.Except for normal group,other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome.24 h after the last medication,serum levels of triiodothyronine (T3),thyroxine (T4),interleukin-2 (IL-2),IL-4,IL-6,IL-10,and interferon-γ (IFN-γ) were all detected;the abortion rate and uterine coefficient were calculated;the pathological morphology of the pregnant uterus was observed;protein expressions of NLRP3,ASC and caspase-1 were detected.RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3,ASC,and pro-caspase-1 were all less than-5 kJ/moL.The animal experiment results showed that compared with normal group,the uterine coefficient and serum levels of IL-4,IL-6 and IL-10 were decreased significantly in model group (P<0.05);the abortion rate and serum levels of T3,T4,IL-2 and IFN-γ as well as protein expressions of NLRP3,ASC and caspase-1 were increased significantly (P<0.05);there were abortion lesions in the pregnant endometrium.Compared with the model group,most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups (P<0.05),and the endometrial miscarriage lesions in pregnancy were improved to varying degrees.CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome,down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2,and up-regulating anti-inflammatory cytokines such as IL-4,IL-6 and IL-10,thereby improving spontaneous abortion with heat syndrome.

Objective:To investigate the role of Pink1/Parkin-induced mitophagy in acute lung injury of exertional heat stroke rats.Methods:Sixty SD rats were randomly divided into four groups, including normal group (CON group), normal Parkin overexpression group (CON+Parkin group), heat stroke group (EHS group) and heat stroke Parkin overexpression group (EHS+Parkin group), with fifteen rats in each group. The rat model of exertional heat stroke was established and the survival curve was drawn. Pulmonary coefficient and pulmonary capillary permeability were detected. HE staining was used to observe the pathological changes of lung tissue. ELISA was used to detect the contents of IL-6, IL-1β, TNF-α and ROS in lung tissue; immunohistochemistry was used to observe apoptosis in lung tissue; Western blot was used to determine the expression of Pink1, Parkin, P62 and LC3 in rat lung tissue, and the LC3II/LC3I ratio was calculated. Single factor multi-level group comparison was performed by single factor analysis of variance, SNK-q method was used to further pairwise comparison between groups.Results:Compared with the normal group, the survival rate of EHS group was decreased ( P<0.001), lung coefficient and pulmonary vascular permeability were increased [(4.39±0.42), (33.38±8.29) μg/g, P<0.05)], lung tissue was exudative and solid, the levels of inflammatory factors IL-6, IL-1β, TNF-α and ROS were significantly increased[(34.31±5.34) pg/mL, (34.03±4.78) pg/mL, (91.64±8.16) pg/mL, (259.01±89.17) U/mg, P<0.05)], and apoptosis was increased. Western and immunohistochemistry results showed that the expressions of Pink1 and Parkin were decreased, co-location of Pink1and Parkin was attenuated, LC3II/LC3I were decreased, and P62 expression was increased. Compared with the EHS group, the survival rate of EHS+Parkin group was significantly increased ( P<0.05), lung coefficient and pulmonary vascular permeability were decreased [(3.83±0.62), (22.49±7.90) μg/g, P<0.05)], exudation and consolidation and other pathological changes were significantly reduced, and the levels of the above inflammatory factors and ROS were significantly decreased [(14.09±3.24) pg/mL, (26.94±2.11) pg/mL、(63.35±11.62) pg/mL, (161.13±26.31) U/mg, P<0.05]. Lung tissue apoptosis was reduced. The co-location of Pink1and Parkin、Parkin expression and LC3II/LC3I ratio were increased ( P<0.05), P62 expression was decreased( P<0.05), while Pink1 expression was not significant different (q=0.75). There was no difference between normal group and normal Parkin overexpression group (q=0.95). Conclusion:Activation of Pink1/Parkin-induced mitophagy can alleviate the acute lung injury in exertional heat stroke rats.

In order to establish a stable in vitro culture platform for chicken small intestine three-dimensional (3D) organoids, in this study, crypt cells were collected from the small intestine of 18-day-old embryos of AA broilers. On the basis of the L-WRN conditioned medium, we optimized the culture conditions of chicken small intestinal organoids by adjusting the proportions of nicotinamide, N-acetylcysteine, LY2157299, CHIR99021, Jagged-1, FGF, and other cytokines to select the medium suitable for the long-term stable growth of the organoids. The optimization results showed that the addition of 1.5 µmol/L CHIR99021 significantly improved the organoid formation efficiency and organoid diameter. When 0.5 µmol/L Jagged-1 was added, a small amount of bud-like tissue appeared in organoids. After the addition of 50 ng/mL FGF-2, the rate of organoid germination was significantly increased. The 1.5 µmol/L CHIR99021, 0.5 µmol/L Jagged-1, and 50 ng/mL FGF-2 added in the medium can cooperate with each other to improve the formation and speed up the proliferation and differentiation of organoids, while improving the stemness maintenance of cells. The morphology, cell types, and culture characteristics of chicken small intestinal organoids were studied by HE staining, transmission electron microscopy, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), indirect immunofluorescence, and immunohistochemistry. The results showed that the 3D organoids of the chicken small intestine cultured in vitro were morphologically consistent with the chicken intestinal tissue and contained differentiated epithelial cells. In summary, we successfully established an in vitro culture system for chicken small intestinal organoids, providing a new method for the subsequent research on chicken intestinal physiology, pathology, and host-pathogen interaction mechanism and the development of relevant drugs.
Animals ; Organoids/metabolism* ; Intestine, Small/drug effects* ; Chickens ; Cell Culture Techniques/methods* ; Culture Media ; Chick Embryo ; Tissue Culture Techniques/methods*

Objective:To investigate the clinical characteristics of patients with malignant tumors and immune checkpoint inhibitors (ICI) related multisystem adverse events as well as therapeutic efficacy of ICI.Methods:The general data, immune-related adverse events (irAE) type, onset time, severity and ICI efficacy of patients with malignant tumors who developed irAE after receiving ICI in China-Japan Friendship Hospital between January 2019 and November 2021 were retrospectively analyzed. All patients were divided into multisystem irAE group and single system irAE group according to whether patients with more than 1 organ or system developed irAE for once. The occurrence of irAE was summarized, and the clinical characteristics of patients were compared. Progression-free survival analysis was not performed owing to the pause of immunotherapy caused by some irAE, so the efficacy of ICI was evaluated by using ICI treatment duration (TD).Results:A total of 47 patients with malignant tumors and irAE were included in this study, with 70 times of irAE in total. The median onset time was 90 d (35 d, 196 d). Among them, 12 patients (25.53%) developed multisystem irAE (32 times of irAE in total); the other 35 patients (74.47%) developed single system irAE (38 times of irAE in total). Cutaneous toxicity for 7 times, thyroid toxicity for 7 times and pulmonary toxicity for 5 times were the most frequent among multisystem irAE group; pulmonary toxicity for 13 times, thyroid toxicity for 12 times and cutaneous toxicity for 5 times were the most frequent among single system irAE group. There were no statistically significant differences in the proportion of patients stratified by age, gender, the combination of other treatments and different body mass between the two groups (all P > 0.05). The median follow-up time was 20 months (9-40 months). The median TD of ICI was 16.00 months (95% CI 3.62-31.22 months) in multisystem irAE group and 4.60 months (95% CI 4.12-11.30 months) in single system irAE group; TD in multisystem irAE group was longer than that in single system irAE group, and the difference was statistically significant ( HR = 0.413, 95% CI 0.202-0.844, P = 0.038). Conclusions:The efficacy of ICI in patients with malignant tumors and multisystem irAE is better than that in those with single system irAE. It suggests that the better efficacy of ICI may be associated with greater risk of irAE. There is no significant difference in the clinical features between multisystem irAE and single system irAE.

Objective:To analyze the impact of previous exposure to macrolide, quinolones and nitroimidazole antibiotics on eradication rate of bismuth quadruple therapy (BQT) in newly diagnosed patients with Helicobacter pylori( H. pylori). Methods:A total of 469 patients with H. pylori initially treated at the Third Hospital of Peking University from September 2017 to August 2020 were retrospectively recruited. The therapeutic regimens were BQT containing clarithromycin/levofloxacin/metronidazole recommended by Chinese guidelines. Clinical data were collected, including general demographic data, exposure history of antibiotics, CYP2C16 metabolic pattern, endoscopic diagnosis, bacterial density, H.pylori resistance, eradication results, etc. Univariate analysis, Chi-square test, Fisher exact probability test, Kruskal-Wallis H test and Logistic regression model were used as statistical methods. Results:Among different eradication therapies, univariate and multivariate analyses suggested that previous exposure to macrolides ( OR=3.37,95 %CI 1.04-10.98, P<0.05) was relevant to the decreased eradication rate of BQT containing clarithromycin. This may be due to increased resistance to clarithromycin ( OR=6.12,95 %CI 3.99-9.40, P<0.01).The previous exposure to quinolones ( OR=3.65, 95 %CI 1.27-10.49, P<0.05) was relevant to the decreased eradication rate of BQT containing levofloxacin, which was probably explained by the increased resistance to levofloxacin ( OR=2.50, 95 %CI 1.69-3.71, P<0.01). But the previous history of nitroimidazole did not impact the efficacy of BQT containing metronidazole. Conclusions:In patients newly diagnosed with H.pylori infection, the previous exposure to macrolide or quinolones antibiotics is related to lower eradiation rates of H. pylori. Although the exposure to nitroimidazole also indicates drug resistance to metronidazole, the clinical efficacy of BQT with metronidazole 400 mg four times a day is not affected.