1.Meconium containing intestinal structures: a histological study using human fetuses
Jun ZHANG ; Zhe-Wu JIN ; Feng HAN ; Ye XU ; Gen MURAKAMI ; Masahito YAMAMOTO ; Shogo HAYASHI
Anatomy & Cell Biology 2026;59(1):105-114
Meconium is changed from defoliated intestinal villi with apoptosis. A meconium corpuscle is a limited architecture in the meconium at the light microscopic level. In histological and immunohistochemical sections of the abdomen from 40 fetuses at 20–31 weeks of gestation, we found 12 fetuses with meconium and examined the architecture.A solid or loose meconium was seen depending on sites. The solid meconium in the colon and rectum contained numerous spherical or rugby ball-like corpuscles comprising of a core with tightly-packed atrophied cells and a laminar fibrous sheath.The solid meconium surrounded and incorporated villi that maintained the original architecture. The loose meconium was seen not only in the stomach and duodenum but also, depending on specimens, in the colon and rectum. It was composed of a large mucosal fold, a single small villus and/or fragmented epithelia. Notably, these mucosal tissues still contained chromogranin-positive gastrointestinal cells and cytokeratin-positive epithelia. A large ring-like meconium was composed of the entirely circular mucosa or epithelia that seemed to be detached along the muscularis mucosae or the basal lamina.A sheath-like fibrous structure in meconium seemed to originate from the lamina propria and basal lamina of villi. A defoliation of villi with apoptosis seemed difficult to explain a detachment of the entirely circular mucosa or epithelia in large fetuses examined. The latter event might require a specific mechanism such as an in utero intussusception in which a proximal side of the colon was invaginated into the distal lumen.
2.Autophagy in different subtypes of breast cancer cells mediated by p-AMPK and its molecular mechanisms
Xin-jiao YANG ; Ru-yao HU ; Zhe XIONG ; Di ZOU ; Jie CAI ; Cong-long XIA ; Zhong-bin BAI ; Hong-ye ZHAO
Chinese Pharmacological Bulletin 2025;41(5):898-907
Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.
3.Prediction and verification of potential mechanism of"ginseng-astragalus-pueraria"horn medicine in protecting pancreatic islet morphology
Ying-qun NI ; Ju-yi LI ; Yi-xuan LIN ; Lei YE ; Zhe ZHANG ; Zhao-hui FANG
Chinese Pharmacological Bulletin 2025;41(3):574-582
Aim To predict and verify the potential mechanism of the compatibility of"ginseng-astragalus-pueraria"in protecting islet morphology and improving insulin resistance by using network pharmacology.Methods The active ingredients and targets of the horn medicine were obtained from three platforms:TC-MSP,TCMIP,and BATMAN.The targets of type 2 dia-betes mellitus(T2DM)were obtained from three plat-forms:TTD,OMIM,and disgeNET.The PPI network was constructed by using the STRING database and Cy-toscape 3.9.1;GO and KEGG analysis were per-formed;POCASA 1.1 was used to predict protein binding sites,and AutoDock Vina1.1.2 was used for docking and experimental verification.Results"Gin-seng-astragalus-pueraria"screened out 2 021 targets,of which 152 were closely related to T2DM,and 10 key genes and the AGE-RAGE signaling pathway were i-dentified.Molecular docking showed that quercetin had good binding to RAGE,INS,and PI3K.Experi-ments showed that the horn drug increased insulin binding rate and secretion index and reduced serum in-sulin level and insulin resistance index.These data benefited from"ginseng-astragalus-pueraria"reducing the expression of AGE-RAGE,activating PI3K-Akt,in-hibiting NF-κB,and reducing the expression of IL-6,IL-1β and TNF-α.Conclusion The study suggests that"ginseng-astragalus-pueraria"regulates the AGE-RAGE/PI3K-Akt/NF-κB signaling pathway,repairs damaged islet morphology,and improves insulin resist-ance.
4.Design and practice of curriculum ideology and politics leading cultivation of postgraduates'innovative abilities
Huihui YUAN ; Wei WANG ; Xulong ZHANG ; Ye CUI ; Yunpeng DOU ; Yan CHEN ; Zhe LYU ; Jie LIU ; Ying SUN
Chinese Journal of Immunology 2025;41(2):444-446,450
The cultivation of innovation ability is not only the essential requirement of graduate education,but also the strate-gic demand of the development of the communist party and our country,and is of great significance to the realization of the Chinese dream of the great rejuvenation of the Chinese nation.Curriculum ideology and politics should run through the whole process of post-graduate innovation ability training.However,the curriculum ideology and politics and postgraduate innovation ability training lack deep integration.It's important for postgraduates'growth and scientific research innovation that the curriculum ideology and politics covers the whole process of scientific research activities.Therefore,this paper focuses on the design and specific implementation schemes of the curriculum ideology and politics on the postgraduate innovative ability training at the respiratory disease research team in the department of medical immunology.It makes a basis for optimizing postgraduate curriculum ideology and politics teaching in the future,which also provides ideas for cultivating innovative talents with both morality and ability in medical specialty.
5.Advances in multi-source surveillance data integration and application of early warning indicators for respiratory infectious diseases
Dazhu HUO ; Ting ZHANG ; Jinzhao CUI ; Xiaochen ZHANG ; Yongtao CHI ; Yanan WANG ; Zhe WANG ; Xin ZHAO ; Ziliang FAN ; Chuchu YE ; Chuangsen FANG ; Yanming LI ; Zhongjie LI ; Weizhong YANG ; Chen WANG
Chinese Journal of Preventive Medicine 2025;59(8):1311-1319
The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.
6.Autophagy in different subtypes of breast cancer cells mediated by p-AMPK and its molecular mechanisms
Xin-jiao YANG ; Ru-yao HU ; Zhe XIONG ; Di ZOU ; Jie CAI ; Cong-long XIA ; Zhong-bin BAI ; Hong-ye ZHAO
Chinese Pharmacological Bulletin 2025;41(5):898-907
Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.
7.Exploration on the Effects of Yiqi Huoxue Huazhuo Jiedu Prescription on Cerebral Ischemia Reperfusion Injury in Rats Based on PERK/ATF4 Signaling Pathway
Tiantian XU ; Ye TIAN ; Shiduo WANG ; Jiayun ZHANG ; Qiming LIU ; Zhe ZHANG ; Xi LI ; Junbiao TIAN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(7):81-87
Objective To investigate the mechanism of Yiqi Huoxue Huazhuo Jiedu Prescription in regulating the endoplasmic reticulum stress PERK/ATF4 signaling pathway to improve cerebral ischemia reperfusion injury in rats.Methods A total of 48 male SD rats were randomly divided into sham-operation group,model group,TCM group and edaravone group,with 12 rats in each group.Cerebral ischemia reperfusion injury rat model was prepared using middle cerebral artery occlusion method,and administration 24 hours after modeling.The edaravone group was given intraperitoneal injection of 1.4 mg/mL edaravone injection,TCM group was given 55 g/(kg·d)of Yiqi Huoxue Huazhuo Jiedu Prescription for gavage,while the sham-operation group and model group were given equal volumes of normal saline for gavage,twice a day for 3 consecutive days.The neurological deficit scores of the rats in each group were observed,TTC staining was used to detect the volume of cerebral infarction,HE staining was used to observe the morphology of brain tissue in the ischemia-reperfusion area,immunohistochemistry staining was used to detect the positive expressions of glucose regulated protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK)and transcription activator factor(ATF)4 in the ischemia-reperfusion area brain tissue,RT-PCR was used to detect the mRNA expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue,Western blot was used to detect the protein expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue.Results Compared with the sham-operation group,the neurological deficit score of the model group rats increased,the volume of cerebral infarction increased,the number of neurons in the ischemia-reperfusion area decreased,the arrangement was loose,and the nuclei were condensed,the mRNA and protein expressions of GRP78,PERK and ATF4 increased,with statistical significance(P<0.05).Compared with the model group,the neurological deficit score of TCM group and edaravone group decreased,the cerebral infarction volume decreased,the number and arrangement of neurons of the brain tissue in the ischemia reperfusion area increased,and nuclear condensation decreased in rats,the mRNA and protein expressions of GRP78,PERK and ATF4 were all reduced,with statistical significance(P<0.05).There was no statistical significance in various indicators between TCM group and the edaravone group(P>0.05).Conclusion Yiqi Huoxue Huazhuo Jiedu Prescription can improve cerebral ischemia reperfusion injury,and its mechanism may be related to down-regulating the expression of PERK/ATF4 signaling pathway and alleviating endoplasmic reticulum stress.
8.Exploring the optimal cutoff values of Kyoto gastritis score,pepsinogen combined with gastrin-17 for predicting Helicobacter pylori positive atrophic gastritis in middle-aged and elderly patients
Chenxuan YE ; Yimin LI ; Peiling LIN ; Zhe XU
China Journal of Endoscopy 2025;31(6):54-63
Objective To investigate the optimal cutoff values of Kyoto gastritis score based on gastroscopy,pepsinogen(PG)combined with gastrin-17(G-17)for predicting Helicobacter pylori positive atrophic gastritis in middle-aged and elderly patients.Methods The subjects of this study were 120 middle-aged and elderly patients admitted,diagnosed with atrophic gastritis through gastroscopy examination and pathological biopsy and proved to be Hp positive via 14C urea breath test from August 2022 to June 2023.All patients were divided into atrophic gastritis group(AG group)with 68 cases and non atrophic gastritis group(non-AG group)with 52 cases according to atrophic gastritis results.The AG group was further divided per Kimura-Takemoto classification into mild AG group(n=12),moderate AG group(n=32)and severe AG group(n=24).Kyoto gastritis score based on gastroscopy was performed in all patients.And test their serum pepsinogen Ⅰ(PGⅠ),pepsinogen Ⅱ(PGⅡ),G-17 levels via chemiluminescence and calculate the PGR=PGⅠ/PGⅡ.Receiver operator characteristic curve(ROC curve)was adopted to assess the value of Kyoto gastritis score and serum PG and G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients.Results There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels between AG group and non-AG group(t=13.38,P=0.000;t=50.84,P=0.000;t=26.44,P=0.000;t=9.44,P=0.000).The Kyoto score of gastritis in AG group was higher than that in non-AG group(P<0.05).The levels of serum PGⅠ,PGR and G-17 in AG group were lower than those in non-AG group(P<0.05).There was no significant difference in serum PGⅡ level between AG group and non-AG group(t=1.24,P=0.219).There were statistically significant differences in Kyoto gastritis score,serum PGⅠ,PGR and G-17 levels among mild AG group,moderate AG group and severe AG group(F=33.95,P=0.000;F=81.99,P=0.000;F=67.36,P=0.001;F=33.50,P=0.004).The mild AG group had a significantly lower Kyoto gastritis score than the moderate AG group and severe AG group(P<0.05),and the moderate AG group had a significantly lower Kyoto gastritis score than the severe AG group(P<0.05).The mild AG group and moderate AG group had significantly higher serum PGⅠ and PGR levels than the severe AG group(P<0.05),and the mild AG group was higher than moderate AG group(P<0.05).The mild AG group had a significantly lower serum G-17 level than the moderate AG group and severe AG group(P<0.05),and there was no significant difference between the moderate AG group and severe AG group(P>0.05).There was no significant difference in serum PGⅡ levels among mild AG group,moderate AG group and severe AG group(F=1.03,P=0.364).The optimal cutoff values of Kyoto gastritis score and serum PGⅠ,PGR and G-17 for predicting atrophic gastritis in middle-aged and elderly patients with Hp positive were 2.78,38.26 μg/L,1.92 and 9.54 pmol/L,respectively.The AUC of Kyoto gastritis score for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.780,the sensitivity was 71.42%,and the specificity was 78.62%.The AUC of PGⅠ for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.757,the sensitivity was 66.27%,and the specificity was 83.25%.The AUC of PGR for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.792,the sensitivity was 76.23%,and the specificity was 87.35%.The AUC of G-17 for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.672,the sensitivity was 60.24%,and the specificity was 74.28%.The AUC of the combination of the four markers for predicting Hp positive atrophic gastritis in middle-aged and elderly patients was 0.871,the sensitivity was 81.28%,and the specificity was 87.36%.Conclusion The Kyoto gastritis score based on gastroscopy,serum PGⅠ,PGR combined with G-17 have good predictive value for Hp positive atrophic gastritis in middle-aged and elderly patients,and the optimal cutoff values for the four markers are 2.78 points,38.26 μg/L,1.92 and 9.54 pmol/L in turn.
9.Biparametric MRI-based peritumoral radiomics for preoperative prediction of extracapsular extension in prostate cancer
Honghao XU ; Qicong DU ; Yuanhao MA ; Xueyi NING ; Baichuan LIU ; Xu BAI ; Di CHEN ; Yun ZHANG ; Zhe DONG ; Chuang JIA ; Xiaojing ZHANG ; Xiaohui DING ; Baojun WANG ; Aitao GUO ; Jian XUE ; Xuetao MU ; Huiyi YE ; Haiyi WANG
Chinese Journal of Radiology 2025;59(9):1055-1062
Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.
10.Exploration on the Effects of Yiqi Huoxue Huazhuo Jiedu Prescription on Cerebral Ischemia Reperfusion Injury in Rats Based on PERK/ATF4 Signaling Pathway
Tiantian XU ; Ye TIAN ; Shiduo WANG ; Jiayun ZHANG ; Qiming LIU ; Zhe ZHANG ; Xi LI ; Junbiao TIAN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(7):81-87
Objective To investigate the mechanism of Yiqi Huoxue Huazhuo Jiedu Prescription in regulating the endoplasmic reticulum stress PERK/ATF4 signaling pathway to improve cerebral ischemia reperfusion injury in rats.Methods A total of 48 male SD rats were randomly divided into sham-operation group,model group,TCM group and edaravone group,with 12 rats in each group.Cerebral ischemia reperfusion injury rat model was prepared using middle cerebral artery occlusion method,and administration 24 hours after modeling.The edaravone group was given intraperitoneal injection of 1.4 mg/mL edaravone injection,TCM group was given 55 g/(kg·d)of Yiqi Huoxue Huazhuo Jiedu Prescription for gavage,while the sham-operation group and model group were given equal volumes of normal saline for gavage,twice a day for 3 consecutive days.The neurological deficit scores of the rats in each group were observed,TTC staining was used to detect the volume of cerebral infarction,HE staining was used to observe the morphology of brain tissue in the ischemia-reperfusion area,immunohistochemistry staining was used to detect the positive expressions of glucose regulated protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK)and transcription activator factor(ATF)4 in the ischemia-reperfusion area brain tissue,RT-PCR was used to detect the mRNA expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue,Western blot was used to detect the protein expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue.Results Compared with the sham-operation group,the neurological deficit score of the model group rats increased,the volume of cerebral infarction increased,the number of neurons in the ischemia-reperfusion area decreased,the arrangement was loose,and the nuclei were condensed,the mRNA and protein expressions of GRP78,PERK and ATF4 increased,with statistical significance(P<0.05).Compared with the model group,the neurological deficit score of TCM group and edaravone group decreased,the cerebral infarction volume decreased,the number and arrangement of neurons of the brain tissue in the ischemia reperfusion area increased,and nuclear condensation decreased in rats,the mRNA and protein expressions of GRP78,PERK and ATF4 were all reduced,with statistical significance(P<0.05).There was no statistical significance in various indicators between TCM group and the edaravone group(P>0.05).Conclusion Yiqi Huoxue Huazhuo Jiedu Prescription can improve cerebral ischemia reperfusion injury,and its mechanism may be related to down-regulating the expression of PERK/ATF4 signaling pathway and alleviating endoplasmic reticulum stress.

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