1.NG2-Glia Cause Diabetic Blood-Brain Barrier Disruption by Secreting MMP-9
Xiaolong LI ; Yan CAI ; Zhu ZHONG ; Maolin LI ; Dong HUANG ; Zhifei QIAO ; Hongli ZHOU ; Zuo ZHANG ; Jiyin ZHOU
Diabetes & Metabolism Journal 2026;50(1):47-61
Background:
Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear.
Methods:
Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA).
Results:
In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939.
Conclusion
The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.
2.Expression of PROM2,RALY and Rab15 in non-small cell lung cancer and their value in predicting the development of bone metastases
Shunsong GONG ; Yan ZHU ; Shi DONG ; Yixin CAI
Journal of Clinical Surgery 2025;33(3):271-274
Objective To investigate the expression of PROM2,RALY and Rab15 in non-small cell lung cancer(NSCLC)and the predictive value for the development of bone metastasis in NSCLC.Methods One hundred and thirty four patients diagnosed with NSCLC in our hospital from Mar 2016 to Feb 2022 were retrospectively analyzed.Patients were divided into bone metastasis(BM)and non-bone metastasis(NBM)groups based on the occurrence of bone metastasis during follow-up.Immunohistochemistry was used to detect the expression of PROM2,RALY,and Rab15 in cancer tissues.The relationship between the expression of these markers and bone metastasis was analyzed,and Cox regression was used to identify risk factors for bone metastasis in NSCLC patients.Results During the follow-up period,43 patients with NSCLC developed bone metastases.Patients with bone metastases had higher age,BMI,percentage of adenocarcinoma,and positive expression of PROM2,RALY and Rab15 than those without bone metastases(P<0.05).Multifactorial Cox analysis showed that age,type of pathology,ECOG,and the positive PROM2 expression were significant risk factors for bone metastases in NSCLC patients(P<0.05).Among patients with bone metastases,those with positive PROM2 expression had a shorter median bone metastasis-free survival time compared to PROM2-negative patients(P<0.05).Conclusion PROM2 positive expression is an independent risk factor for bone metastasis in NSCLC patients,and is closely related to their prognosis.
3.The value of total volume response and total mass response in the therapeutic evaluation of lung metastasis of hepatocarcinoma
Jun-cheng WAN ; Cai-hong YU ; Chang-yu LI ; Yong-jie ZHOU ; Wei ZHANG ; Jian-hua WANG ; Zhi-ping YAN ; Guo-wei YANG ; Zhuo-yang FAN ; Xu-dong QU
Fudan University Journal of Medical Sciences 2025;52(2):201-208,231
Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.
4.The value of total volume response and total mass response in the therapeutic evaluation of lung metastasis of hepatocarcinoma
Jun-cheng WAN ; Cai-hong YU ; Chang-yu LI ; Yong-jie ZHOU ; Wei ZHANG ; Jian-hua WANG ; Zhi-ping YAN ; Guo-wei YANG ; Zhuo-yang FAN ; Xu-dong QU
Fudan University Journal of Medical Sciences 2025;52(2):201-208,231
Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.
5.CiteSpace and VOSviewer-based visualization and analysis of near-infrared brain functional imaging in field of rehabilitation medicine research
Cai-yang DING ; Guo-dong SUN ; Meng-yuan LI ; Shuai MA ; Tong ZHANG ; Hong-yan WANG
Chinese Medical Equipment Journal 2025;46(11):62-70
The academic literature on near-infrared brain functional imaging in the field of resuscitation medicine published in the Web of Science core collection,MEDLINE and PubMed databases from January 2006 to May 2025 were collected,which underwent statistical and visualized analyses with CiteSpace and VOSviewer software in terms of annual publication trends,authors,countries/regions,institutions,co-cited literature and keyword co-occurrence,clustering and emergence.It was pointed out that the overall number of publications in this research field had been on the rise in the past two decades.Stroke patients were the core research group in this field,and cortical activation mechanisms had always been the focus of research.Motor imagery was a high-frequency research content in this field,and multimodal technology integration was the trend of research in this field.New research ideas and methods were provided for relevent research in the field of rehabilitation medicine in China.
6.Expression of PROM2,RALY and Rab15 in non-small cell lung cancer and their value in predicting the development of bone metastases
Shunsong GONG ; Yan ZHU ; Shi DONG ; Yixin CAI
Journal of Clinical Surgery 2025;33(3):271-274
Objective To investigate the expression of PROM2,RALY and Rab15 in non-small cell lung cancer(NSCLC)and the predictive value for the development of bone metastasis in NSCLC.Methods One hundred and thirty four patients diagnosed with NSCLC in our hospital from Mar 2016 to Feb 2022 were retrospectively analyzed.Patients were divided into bone metastasis(BM)and non-bone metastasis(NBM)groups based on the occurrence of bone metastasis during follow-up.Immunohistochemistry was used to detect the expression of PROM2,RALY,and Rab15 in cancer tissues.The relationship between the expression of these markers and bone metastasis was analyzed,and Cox regression was used to identify risk factors for bone metastasis in NSCLC patients.Results During the follow-up period,43 patients with NSCLC developed bone metastases.Patients with bone metastases had higher age,BMI,percentage of adenocarcinoma,and positive expression of PROM2,RALY and Rab15 than those without bone metastases(P<0.05).Multifactorial Cox analysis showed that age,type of pathology,ECOG,and the positive PROM2 expression were significant risk factors for bone metastases in NSCLC patients(P<0.05).Among patients with bone metastases,those with positive PROM2 expression had a shorter median bone metastasis-free survival time compared to PROM2-negative patients(P<0.05).Conclusion PROM2 positive expression is an independent risk factor for bone metastasis in NSCLC patients,and is closely related to their prognosis.
7.CiteSpace and VOSviewer-based visualization and analysis of near-infrared brain functional imaging in field of rehabilitation medicine research
Cai-yang DING ; Guo-dong SUN ; Meng-yuan LI ; Shuai MA ; Tong ZHANG ; Hong-yan WANG
Chinese Medical Equipment Journal 2025;46(11):62-70
The academic literature on near-infrared brain functional imaging in the field of resuscitation medicine published in the Web of Science core collection,MEDLINE and PubMed databases from January 2006 to May 2025 were collected,which underwent statistical and visualized analyses with CiteSpace and VOSviewer software in terms of annual publication trends,authors,countries/regions,institutions,co-cited literature and keyword co-occurrence,clustering and emergence.It was pointed out that the overall number of publications in this research field had been on the rise in the past two decades.Stroke patients were the core research group in this field,and cortical activation mechanisms had always been the focus of research.Motor imagery was a high-frequency research content in this field,and multimodal technology integration was the trend of research in this field.New research ideas and methods were provided for relevent research in the field of rehabilitation medicine in China.
8.Experience in Staged Differentiation and Treatment of Cirrhotic Ascites Based on the Theory of Tonification and Purging
Haihang DONG ; Yujie CAI ; Huiqin ZHANG ; Yan CHEN ; Yuying TU ; Dongling WANG ; Yinqiang ZHANG
Journal of Traditional Chinese Medicine 2025;66(5):532-536
It is believed that patients with cirrhotic ascites exhibit a pathological mechanism characterized by the decline of healthy qi and the accumulation of pathogenic factors. Clinically, treatment should be based on the theory of tonification and purging, with a staged approach distinguishing between the active phase and the remission phase. The balance between tonification and purging should be adjusted according to the progression of pathogenic and healthy actors. In the acute phase, purging should take precedence over tonification, using purging as a means of tonification to facilitate the flow of water and qi through the triple energizer. The severity of water retention, dampness, blood stasis, and heat should be carefully assessed to ensure thorough elimination of pathogenic factors while avoiding harm to healthy qi. Medication adjustments should be made once the pathogenic factors are significantly weakened. In the remission phase, an integrated approach combining both tonification and purging should be adopted, incorporating purging within tonification to clear residual pathogens and prevent recurrence. Concurrently, proactive treatment of the underlying disease is essential to achieve complete recovery and prevent the recurrence of ascites.
9.Analysis of chemical constituents of Dendrobium huoshanense flowers based on LC-MS and GC-MS
Le-yuan JI ; Qi-yan LIN ; Jin-xiang WU ; Qian WANG ; Bang-xing HAN ; Ye-cai WANG ; Dong LIU
Chinese Traditional Patent Medicine 2025;47(11):3660-3670
AIM To establish LC-MS and GC-MS method and analyze the chemical constituents of Dendrobium huoshanense C.Z.Tang & S.J.Cheng flowers.METHODS LC-MS was performed on a Zorbax Eclipse C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of water(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min,and electrospray ionization was operated in both positive and negative ion modes.The GC-MS employed headspace solid-phase microextraction for sample preparation,and the analysis was performed on an HP-5MS column(30 m×0.25 mm,0.25 μm),with the following temperature program:initial temperature 50 ℃(held for 2 min),increased at 5 ℃/min to 180 ℃(held for 5 min),then raised at 10 ℃/min to 250 ℃(held for 5 min),and electron impact ion source was employed.RESULTS A total of 62 compounds were identified by LC-MS,including 35 flavonoids,4 coumarins,6 alkaloids,6 terpenoids,3 amino acids,2 polyphenols,2 ketones and 4 others.A total of 101 volatile components were identified by GC-MS,including ketones,aldehydes,alcohols,esters,ethers,and acid.CONCLUSION This method can comprehensively analyze the chemical constituents of D.huoshanense flowers,and provide a scientific basis for elucidating its pharmacodynamic material basis.
10.Objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease
Zhaoxi DONG ; Yang SHI ; Jiaming SU ; Yaxuan WEN ; Zheyu XU ; Xinhui YU ; Jie MEI ; Fengyi CAI ; Xinyue ZANG ; Yan GUO ; Chengdong PENG ; Hongfang LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):398-411
Objective:
To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD).
Methods:
A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status.
Results:
No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups.
Conclusion
Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.


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