1.Effects of Metformin on C-C motif chemokine ligand-2/C-C motif chemokine receptor-2 axis on the balance of type 17 helper T cells/regulatory T cells in diabetic rats
Qianhua LIU ; Junhong ZHOU ; Chaomin LI ; Yu WU
Chinese Journal of Diabetes 2025;33(8):623-630
Objective To explore the impact of Metformin(Met)on the balance of type 17 helper T cells(Th17)/regulatory T cells(Treg)in DM rats by regulating the C-C motif chemokine ligand 2(CCL2)-C-C motif chemokine receptor 2(CCR2)axis.Methods A total of 50 SD rats were randomly divided into normal control(NC)group,model(Mod)group,Met(100 mg/kg)group,Met+empty vector(Met+oe-NC)group,and Met+CCL2 overexpression(Met+oe-CCL2)group,with 10 rats in each group.The changes of FBG evaluated in each group,and the pathological changes of pancreatic islet tissue were assessed using hematoxylin-eosin(HE)staining followed by histological scoring.The ratio of Th17/Treg in peripheral blood was detected by flow cytometry.ELISA was used to measure the serum levels of IL-17,TNF-α,TGF-β and IL-10.Immunofluorescence was used to detect the proportion of Th17 and Treg in pancreatic tissue.RT-PCR and Western blot were used to detect the mRNA and protein expression of ROR-γt,forkhead box P3(FOXP3),CCL2 and CCR2 in pancreatic tissue.Results The islet structure was intact and the boundary was clear,and there was no pathological damage in the NC group.In the Mod group,the islet tissue exhibited significant pathological damage,characterized by disrupted architecture,reduced volume,and blurred boundaries with surrounding tissues.Additionally,the cells in the islet displayed marked disorganization and substantial loss.Compared with the Mod group,the pathological damage of the islet tissue was alleviated in the Met and Met+oe-NC group.Compared with the Met group,the pathological damage was aggravated in the Met+oe-CCL2 group.Compared with the NC group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein expression were higher(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were lower in the Mod group(P<0.05).Compared with the Mod group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were lower(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met and Met+oe-NC groups(P<0.05).Compared with the Met group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were higher(P<0.05),and TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met+oe-CCL2 group(P<0.05).Conclusions Metformin can promote Th17/Treg cell balance drift towards Treg direction by inhibiting the activation of CCL2-CCR2 signal axis,thereby preventing the occurrence and development of inflammatory reactions,alleviating pancreatic islet damage,and improving the glucose metabolism in DM rats.
2.Differentiation and treatment of Hashimoto thyroiditis based on the theory of"qi cycle in round"
Wenlin MA ; Jing SUN ; Xiqiao ZHOU ; Qianhua YAN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1419-1425
The theory of"qi cycle in round"originates from HUANG Yuanyu's Sisheng Xinyuan,which takes qi monism as the philosophical foundation,and constructs a qi circulation system with the spleen and stomach as the hub,linking the liver,heart,lung,and kidney on the basis of the gasification theory of Huangdi Neijing.Based on theory of"qi cycle in round,"the pathogenesis of Hashimoto thyroiditis begins with liver depression,leading to liver and spleen imbalance,which in turn develops into spleen and kidney deficiency.In the treatment,guided by the principle of"treating same disease with different methods,"combined with objective indicators such as the thyroid function,autoantibody,and ultrasound imaging characteristics,Hashimoto thyroiditis was treated in three stages:early,middle,and late stages.In the early stage,characterized by liver depression and qi stagnation,therapy focuses on regulating wood qi to facilitate the pivot;in the middle stage,marked by liver depression and spleen deficiency,and the method of pungent opening and bitter descending should be adopted to restore the ascending and descending of the spleen and stomach;in the late stage,characterized by spleen and kidney yang deficiency,treatment aims to warm the kidney and tonify the spleen,which helps"qi cycle in round"and restores the normal state of qi transformation of zang-fu viscera.Stage-specific differentiation and treatment aims to restore the qi transformation of zang-fu viscera,promote"qi cycle in round,"improve thyroid function,and delay the progression of Hashimoto thyroiditis,thereby providing insights and methods for clinical differentiation and treatment of this disease.
3.Differentiation and treatment of Hashimoto thyroiditis based on the theory of"qi cycle in round"
Wenlin MA ; Jing SUN ; Xiqiao ZHOU ; Qianhua YAN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1419-1425
The theory of"qi cycle in round"originates from HUANG Yuanyu's Sisheng Xinyuan,which takes qi monism as the philosophical foundation,and constructs a qi circulation system with the spleen and stomach as the hub,linking the liver,heart,lung,and kidney on the basis of the gasification theory of Huangdi Neijing.Based on theory of"qi cycle in round,"the pathogenesis of Hashimoto thyroiditis begins with liver depression,leading to liver and spleen imbalance,which in turn develops into spleen and kidney deficiency.In the treatment,guided by the principle of"treating same disease with different methods,"combined with objective indicators such as the thyroid function,autoantibody,and ultrasound imaging characteristics,Hashimoto thyroiditis was treated in three stages:early,middle,and late stages.In the early stage,characterized by liver depression and qi stagnation,therapy focuses on regulating wood qi to facilitate the pivot;in the middle stage,marked by liver depression and spleen deficiency,and the method of pungent opening and bitter descending should be adopted to restore the ascending and descending of the spleen and stomach;in the late stage,characterized by spleen and kidney yang deficiency,treatment aims to warm the kidney and tonify the spleen,which helps"qi cycle in round"and restores the normal state of qi transformation of zang-fu viscera.Stage-specific differentiation and treatment aims to restore the qi transformation of zang-fu viscera,promote"qi cycle in round,"improve thyroid function,and delay the progression of Hashimoto thyroiditis,thereby providing insights and methods for clinical differentiation and treatment of this disease.
4.Effects of Metformin on C-C motif chemokine ligand-2/C-C motif chemokine receptor-2 axis on the balance of type 17 helper T cells/regulatory T cells in diabetic rats
Qianhua LIU ; Junhong ZHOU ; Chaomin LI ; Yu WU
Chinese Journal of Diabetes 2025;33(8):623-630
Objective To explore the impact of Metformin(Met)on the balance of type 17 helper T cells(Th17)/regulatory T cells(Treg)in DM rats by regulating the C-C motif chemokine ligand 2(CCL2)-C-C motif chemokine receptor 2(CCR2)axis.Methods A total of 50 SD rats were randomly divided into normal control(NC)group,model(Mod)group,Met(100 mg/kg)group,Met+empty vector(Met+oe-NC)group,and Met+CCL2 overexpression(Met+oe-CCL2)group,with 10 rats in each group.The changes of FBG evaluated in each group,and the pathological changes of pancreatic islet tissue were assessed using hematoxylin-eosin(HE)staining followed by histological scoring.The ratio of Th17/Treg in peripheral blood was detected by flow cytometry.ELISA was used to measure the serum levels of IL-17,TNF-α,TGF-β and IL-10.Immunofluorescence was used to detect the proportion of Th17 and Treg in pancreatic tissue.RT-PCR and Western blot were used to detect the mRNA and protein expression of ROR-γt,forkhead box P3(FOXP3),CCL2 and CCR2 in pancreatic tissue.Results The islet structure was intact and the boundary was clear,and there was no pathological damage in the NC group.In the Mod group,the islet tissue exhibited significant pathological damage,characterized by disrupted architecture,reduced volume,and blurred boundaries with surrounding tissues.Additionally,the cells in the islet displayed marked disorganization and substantial loss.Compared with the Mod group,the pathological damage of the islet tissue was alleviated in the Met and Met+oe-NC group.Compared with the Met group,the pathological damage was aggravated in the Met+oe-CCL2 group.Compared with the NC group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein expression were higher(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were lower in the Mod group(P<0.05).Compared with the Mod group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were lower(P<0.05),while TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met and Met+oe-NC groups(P<0.05).Compared with the Met group,the levels of FBG,Th17/Treg ratio,IL-17,TNF-α,Th17 infiltration rate,ROR-γt,CCL2,and CCR2 mRNA and protein were higher(P<0.05),and TGF-β,IL-10,Treg infiltration rate,FOXP3 mRNA and protein expression were higher in the Met+oe-CCL2 group(P<0.05).Conclusions Metformin can promote Th17/Treg cell balance drift towards Treg direction by inhibiting the activation of CCL2-CCR2 signal axis,thereby preventing the occurrence and development of inflammatory reactions,alleviating pancreatic islet damage,and improving the glucose metabolism in DM rats.
5.The value of POSSUM score system in predicting postoperative complications in elderly patients and its correlation with Clavien-Dindo classification
Qianhua ZHOU ; Liang ZHANG ; Yiming SHI ; Haiyang WANG
Chongqing Medicine 2024;53(4):542-546,554
Objective To explore the value of the Physiology and Surgical Severity Score(POSSUM)scoring system in predicting postoperative complications in elderly patients with thoracic surgery,and to ana-lyze its correlation with Clavien-Dindo classification.Methods The data of 182 elderly patients who under-went thoracic surgery in this hospital from October 2019 to March 2023 were retrospectively analyzed.They were divided into the complication group and the non-complication group according to whether there were complications after surgery.The baseline data and POSSUM score of the two groups were analyzed,and the receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of POSSUM for post-operative complications in elderly patients.POSSUM of patients with different Clavien-Dindo classification was compared,and the correlation between POSSUM and Clavien-Dindo classification analyzed.Results The incidence of pulmonary infection was the highest in the complication group,followed by hypoproteinemia.POSSUM in the complication group was higher than that in non-complication group before operation,and the difference was statistically significant(P<0.05).The ROC curve showed that the area under curve(AUC)value of POSSUM was 0.829;In the complication group,according to Clavien-Dindo classification,there were 5 cases of grade Ⅰ,47 cases of grade Ⅱ,8 cases of grade Ⅱ Ⅲ,7 cases of grade Ⅳ and 8 cases of grade V,the difference was statistically significant(P<0.05).The correlation analysis showed that POSSUM score was positively correlated with Clavien-Dindo classification(r>0.513,P<0.05).Conclusion The POSSUM scoring system has a high value in predicting postoperative complications in elderly patients with thoracic surgery.
6.Review of animal models of non-steroidal anti-inflammatory drug-induced gastric ulcer
Wen WANG ; Yujun HOU ; Yunzhou SHI ; Lu WANG ; Qianhua ZHENG ; Siyuan ZHOU ; Ying CHEN ; Luqiang SUN ; Shuai CHEN ; Xiangyun YAN ; Yanqiu LI ; Ying LI
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):1084-1092
Gastric ulcer is a common digestive system disease,and the long-term use of non-steroidal anti-inflammatory drugs(NSAIDs)is the second most important cause.NSAID-induced gastric ulcer animal models are key experimental tools for studying the pathogenesis,corresponding treatment method,and effective mechanisms of NSAID-induced gastrointestinal injury.However,there are currently a lack of reviews on NSAID-induced gastric ulcer animal models.This review summarizes and compares the relevant literature on animal research into indomethacin-and aspirin-induced gastric ulcers in the past 10 years,including the selection of experimental animals,drug solvents,and specific modeling method.The limitations of current models,such as the cumbersome modeling method,incomplete modeling details,inadequate models for clinical use,and lack of comparative drug research,are discussed.Feasible solutions are proposed with the aim of providing an effective reference for research in this field.
7.Application of endoscopic narrow-band imaging in the early diagnosis of throat malignant tumors
Xiangwen ZHANG ; Qianhua PENG ; Ruixiang CHEN ; Penglong ZHAO ; Mengyan ZHOU
Chinese Journal of Primary Medicine and Pharmacy 2020;27(23):2855-2858
Objective:To explore the application of endoscopic narrow-band imaging(NBI) in the early diagnosis of throat malignant tumors.Methods:From January 2014 to December 2019, 512 patients with suspected benign or malignant diseases of the throat in the First People's Hospital of Wenling were selected, and all patients were performed white light endoscopy and NBI endoscopy.The biopsies were taken for pathological examination.The histopathological results were seemed as gold standard for diagnosis.Results:NBI endoscopy was superior to white light endoscope in terms of microvascular morphology and lesion outline(χ 2=457.497, 293.209, all P<0.05). The diagnostic coincidence rate, sensitivity and negative coincidence rate of NBI endoscope for malignant tumors were higher than those of white light endoscope(χ 2=10.131, 6.197, 4.084, all P<0.05). The sensitivity of NBI endoscope type Ⅰ-Ⅱ in the diagnosis of benign lesions was 90.65%, and the specificity was 96.88%.The sensitivity and specificity of NBI endoscope type Ⅲ-Ⅳ in the diagnosis of mild-moderate dysplasia were 80.99% and 97.52%, respectively.The sensitivity and specificity of NBI endoscopy type Va in the diagnosis of severe atypical hyperplasia were 15.18% and 98.54%, respectively.The sensitivity and specificity of NBI endoscope Va-c in the diagnosis of invasive cancer were 93.24% and 96.93%, respectively. Conclusion:Compared with white light endoscope, NBI endoscope can more clearly show the outline of lesions and submucosal blood vessels, and can more accurately diagnose malignant tumors in the throat, especially can more recognized the pre-cancerous lesions and early malignant tumors.It has important clinical application value in early diagnosis of malignant tumor in the throat.
8.Application of local gyrification index in the early diagnosis of Alzheimer disease
Haimeng HU ; Yingru LYU ; Qiao LI ; Bijing ZHOU ; Qianhua ZHAO ; Huijin HE ; Ran Xiaoyuan2Guo FENG
Chinese Journal of Radiology 2019;53(5):345-350
Objective To evaluate the role of local gyrification index (LGI) in the early diagnosis of Alzheimer disease(AD). Methods Thirty‐five amnestic‐type mild cognitive impairment patients (aMCI group), 34 mild AD patients (mild AD group) and 33 healthy volunteers (normal control group) were studied. All patients underwent high resolution MRI examination and mini‐mental state examination (MMSE). Using surface‐based morphometry, the FreeSurfer was employed to access LGI of vertex over every participant′s whole cortical surface, then we calculated the mean LGI (mLGI) of each subject′s left and right hemisphere separately. Taking age, gender and educational year as covariance, analysis of covariance was used to compare the difference of mLGI of left and right brain among 3 groups, then Bonferroni was done between every two groups. Analysis of covariance was applied to compare the difference of LGI of every participant among 3 groups, and Monte Carlo method was employed to perform multiple comparison corrections. The correlations between the MMSE scores and LGIs of the three groups were analyzed. Results Compared with normal control group(left 3.03±0.12,right 3.02±0.13), the mLGI of hemispheres in mild AD group(left 2.94±0.11,right 2.93±0.10) decreased respectively(P<0.05). The difference of mLGI of hemispheres between aMCI group(left 2.96 ± 0.10, right 2.96 ± 0.09) and normal control group had no statistical significance(P>0.05). The difference of mLGI of hemispheres between aMCI group and mild AD group also had no statistical significance(P>0.05). The aMCI group showed decrease of LGI in some brain regions located at the right temporal lobe, bilateral frontal and parietal lobe compared with the normal control group. While compared with aMCI group, decreased LGIs was presented in some brain regions located at bilateral temporal, occipital, frontal lobe and the right parietal lobe of mild AD group. There was a positive correlation between MMSE scores and LGIs of some brain regions in the bilateral temporal, occipital lobe, the left frontal lobe and the right parietal lobe in the three groups. Conclusion LGI is conductive in the early diagnosis of AD and can serve as an imaging marker for monitoring disease progresses.
9.Development and validity of Huashan Naming Test
Chunying LIN ; Qihao GUO ; Qianhua ZHAO ; Yan ZHOU ; Zhen HONG
Chinese Journal of Behavioral Medicine and Brain Science 2011;20(2):183-185
Objective To present the development of the Naming test tool ( Huashan Naming Test, HNT)for Chinese cultural and by amnestic mild cognitive impairment ( aMCI ) and mild Alzheimer' s disease (AD) between the detection of memory decline,and to analyze the validity of its trial.Methods 100 normal elders from communities in Shanghai, 100 patients with amnestic mild cognitive impairment (aMCI), and 95 patients with mild Alzheimer's disease (AD) who received an education of junior high school or above and were evaluated by neuropsychological tests including mini mental state examination ( MMSE), auditory verbal memory test, Huashan Naming tests etc.8 cognitive tests.The groups of MCI and AD patients finished cranial MRI.100 items with HNT including 20 animals,10 vegetables,10 fruits ,20 tools ,20 household , 10 vehicles, 10 stationery.Results 1.HNT items to determine: 22 items were excluded due to the completion of the three groups were not significantly different; 8 items were excluded due to the completion of the normal elderly group was lower than 75%; 10 items were excluded from the analysis of variance Fvalue of the minimum value.The remaining 60 items,according to the size of the arrangement and completion rates were divided into two versions of odd and even, respectively HNT-Ⅰ and HNT-Ⅱ.2.HNT characteristics:in normal elderly group age, sex were found to had no significant factors affecting overall scores of HNT-Ⅰ and HNT-Ⅱ but level of education, MMSE score was significantly correlated (P <0.05).As cut-off score ≤ 26 for spontaneous naming of HNT,the sensitivities of HNT-Ⅰ for aMCI ,mild AD were 44%, 84% respectively, specificities were all around 84%; the sensitivities of HNT-Ⅱ for aMCI , mild AD were 56% ,83% respectively,specificities were all around 80%.Conclusion HNT is a Chinese cultural background,time-consuming short and good name validity test,and it is worth further promoting the application.
10.Longitudinal study of two subtypes of mild cognitive impairment
Meirong CHEN ; Qihao GUO ; Yan ZHOU ; Qianhua ZHAO ; Ding DING ; Zhen HONG
Chinese Journal of Neurology 2010;43(5):351-354
Objective To investigate the conversion rate of subtypes of amnestic mild cognitive impairment (aMCI) to Alzheimer' s disease (AD) and assess the contribution of neuropsychological disturbance in progression from MCI to AD over 2 years. Method Subjects from memory clinic of Huashan hospital including 130 of who met the operational criteria for Mayo Clinic defined aMCI by neuropsychological tests covering global cognitive function, executive function, memory function, language function and visual spatial skills. They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after about 2 years. Diagnosis for dementia was based on National Institute of Neurological and Communicative Disorders and Stroke; Alzheimer' s Disease and Related Disorders Association (NINCDS-ADRDA) criteria. Results Forty-four cases of 130 (33. 8% ) elder people with aMCI converted to probable AD with 17 aMCI-s and 27 aMCI-m subjects within an average 23.8 (6. 8 ) months. There was significant difference between the reversion rate of aMCI-s and aMCI-m (26. 2% vs 42. 9%, x2 = 3.957,P = 0. 047). Moreover, as the disease progressing,the two groups declined similarly in memory and executive function while in the aMCI-s group, the function of spatial structure relatively reserved in aMCI-s but function of language and attention diminished faster, and in the aMCI-m group, the ability of spatial structure declined even more significantly. Conclusion The aMCI-m is more likely to progress to AD than aMCI-s and it' s necessary to divide aMCI into aMCI-s and aMCI-m to help determine prognosis.

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