1.Effects of Zuogui Jiangtang Qingzhi Formula on the cGAS/STING/TBK1 signaling pathway in mice with type 2 diabetes mellitus combined with non-alcoholic fatty liver disease
Yangyang GOU ; Jiahui MA ; Cong CHEN
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):370-378
Objective:
To investigate how Zuogui Jiangtang Qingzhi Formula (ZGJTQZF), a traditional Chinese medicine compound for lowering blood glucose levels and clearing lipids based on Zuogui Pill, regulates the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)/TANK-binding kinase 1 (TBK1) signaling pathway to improve type 2 diabetes mellitus combined with non-alcoholic fatty liver disease.
Methods:
According to fasting blood glucose (FBG) levels, body weight, and sex, 40 MKR mice, with half being male and the other half female, were randomly divided into four groups: blank, model, ZGJTQZF (29.6 g/kg), metformin + simvastatin ([65.0+ 2.6] mg/kg), 10 mice per group, and a normal group consisting of 10 age-matched FVB mice. Mice in all groups, except in the normal and blank groups, were fed a high-fat diet for 8 weeks to induce the disease model. Each group received daily gavage of the respective treatments for 8 weeks after successful modeling. Various parameters were measured, including FBG, liver function (alanine aminotransferase [ALT] and aspartate transaminase [AST]), and blood lipids (triglyceride [TG] and total cholesterol [TC]). Serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined using enzyme-linked immunosorbent assays. Histological liver changes were examined using transmission electron and optical microscope. cGAS, STING, and TBK1 protein and mRNA expression levels in liver tissues were detected using Western blotting and real-time PCR, respectively.
Results:
Compared with the normal group, the model group exhibited significant fat accumulation in hepatocytes and liver damage. Additionally, FBG, ALT, AST, serum TNF-α, IL-6, cGAS, STING and TBK1 expression levels in liver tissues were significantly elevated (P<0.05). Treatment with ZGJTQZF and metformin + simvastatin significantly improved FBG, ALT, AST, TG, TC, TNF-α, and IL-6 (P<0.01). Histologically, hepatic steatosis was notably alleviated. Expression of protein and mRNA of cGAS, STING, and TBK1 in liver tissues was significantly reduced (P<0.05).
Conclusion
ZGJTQZF improves lipid and glucose metabolism, mitigates liver injury, and reduces inflammatory markers in MKR mice. These effects may be mediated through the regulation of the cGAS/STING/TBK1 signaling pathway.
2.Comparison of Therapeutic Effect of Different Preparation Processes of Baihe Dihuangtang on Depressed Mice Based on Q-Marker
Yan LIU ; Jiameng LIU ; Jiahui PENG ; Dan LI ; Shengjun MA ; Jingfan YANG ; Yu FU ; Guangwei ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):159-167
ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress(CUMS), to evaluate the quality marker(Q-Marker) and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography(HPLC) was used to establish the characteristic profiles of Baihe Dihuangtang, and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group, model group, fluoxetine group(3 mg·kg-1), low and high dose groups of ancient process(6.5, 26 g·kg-1), and low and high dose groups of modern process(6.5, 26 g·kg-1), with 10 mice in each group. Except for the normal group, CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling, administration groups were given the corresponding drugs by gavage every day, and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded, tail suspension test and open field test were used to evaluate the depressive behavior of mice, and enzyme-linked immunosorbent assay(ELISA) was employed to determine the contents of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established, the similarity between the two was 0.951, and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that, compared with the normal group, the model group showed increased immobility time in the tail suspension test, reduced total movement distance in the open field test, and elevated IL-1β, IL-6 and TNF-α levels in the serum(P<0.01). Compared with the model group, the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise, and the levels of IL-1β, IL-6 and TNF-α in serum were significantly reduced(P<0.05, P<0.01). Baihe Dihuangtang prepared by the two processes both had antidepressant effects, and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content, and the pharmacological effects are consistent, indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.
3.Comparison of Therapeutic Effect of Different Preparation Processes of Baihe Dihuangtang on Depressed Mice Based on Q-Marker
Yan LIU ; Jiameng LIU ; Jiahui PENG ; Dan LI ; Shengjun MA ; Jingfan YANG ; Yu FU ; Guangwei ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):159-167
ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress(CUMS), to evaluate the quality marker(Q-Marker) and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography(HPLC) was used to establish the characteristic profiles of Baihe Dihuangtang, and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group, model group, fluoxetine group(3 mg·kg-1), low and high dose groups of ancient process(6.5, 26 g·kg-1), and low and high dose groups of modern process(6.5, 26 g·kg-1), with 10 mice in each group. Except for the normal group, CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling, administration groups were given the corresponding drugs by gavage every day, and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded, tail suspension test and open field test were used to evaluate the depressive behavior of mice, and enzyme-linked immunosorbent assay(ELISA) was employed to determine the contents of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established, the similarity between the two was 0.951, and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that, compared with the normal group, the model group showed increased immobility time in the tail suspension test, reduced total movement distance in the open field test, and elevated IL-1β, IL-6 and TNF-α levels in the serum(P<0.01). Compared with the model group, the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise, and the levels of IL-1β, IL-6 and TNF-α in serum were significantly reduced(P<0.05, P<0.01). Baihe Dihuangtang prepared by the two processes both had antidepressant effects, and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content, and the pharmacological effects are consistent, indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.
4.New Advances in the Use of 18F-FET PET in the Diagnosis and Management of Adult High-Grade Gliomas
Qingqing HAN ; Tuo LI ; Haiqun XING ; Chao REN ; Jiahui LIU ; Yu WANG ; Wenbin MA ; Xin CHENG ; Li HUO
JOURNAL OF RARE DISEASES 2024;3(1):102-107
Gliomas are the most common primary intracranial tumors in adults, among which high-grade glioma patients are characterized by short survival and poor prognosis. The diagnosis, treatment, evaluation of effective treatments, and prognosis prediction of high-grade gliomas are of great significance for improving patient survival. Conventional enhanced magnetic resonance imaging has deficiencies in delineating tumor extent, identifying tumor progression and treatment-related changes. Therefore, there is a broad consensus to incorporate amino acid PET, and 18F-FET PET inparticular, into the diagnostic and therapeutic process of high-grade gliomas. In this article, we review the new research progress of 18F-FET PET in the diagnosis and treatment of adult high-grade glioma in recent years.
5.Compound cottonrose hibiscus leaf gel plaster of optimal"Xiaozhongsan"formulation for knee synovitis
Wei YAN ; Bo KONG ; Xiaobing XI ; Yong XU ; Youji JIA ; Beite RUAN ; Jiahui ZHANG ; Honghong MA ; Zhongwei LI
Chinese Journal of Tissue Engineering Research 2024;28(10):1580-1585
BACKGROUND:Previous studies have confirmed that the new compound cottonrose hibiscus leaf gel plaster has a good effect in the treatment of acute soft tissue swelling. OBJECTIVE:To observe the clinical efficacy of compound cottonrose hibiscus leaf gel plaster in the treatment of synovitis of the knee joint. METHODS:Seventy-two patients with knee synovitis were selected from Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2019 to May 2021.These patients were randomly divided into a trial group and a control group,with 36 cases in each group.The trial group was treated with compound cottonrose hibiscus leaf gel plaster,once a day,12 hours each time,while the control group was treated with Diclofenac Diethylamine Emulgel,twice a day.After 28 days of treatment,visual analog scale score,WOMAC Osteoarthritis Index score,quality of life score(SF-36),thickness of knee synovium and comprehensive curative effect were compared between the two groups. RESULTS AND CONCLUSION:(1)Visual analog scale scores after treatment were lower than those before treatment(P<0.05).Visual analog scale scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).The WOMAC Osteoarthritis Index scores of the two groups after treatment were lower than those before treatment(P<0.05),and the WOMAC Osteoarthritis Index scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).(3)The SF-36 quality of life score in the two groups after 28 days of treatment was higher than that before treatment(P<0.05).SF-36 quality of life score in the trial group after 28 days of treatment was higher than that in the control group(P<0.05).(4)After 28 days of treatment,the thickness of knee synovium in the trial group was less than that in the control group(P<0.05),and the effective rate in the trial group was higher than that in the control group(P<0.05).(5)These findings indicate that compared with Diclofenac Diethylamine Emulgel,the compound cottonrose hibiscus leaf gel plaster can better relieve knee pain,enhance knee joint function,reduce synovial hyperplasia,and elevate the overall quality of life of patients.
6.The correlation between the ratio of C-reactive protein to albumin and Wei-Qi-Ying-Xue syndrome in patients with severe COVID-19
Lan LI ; Caijun WU ; Linqin MA ; Yuanzhen JIAN ; Jiahui SU ; Junxi LIU ; Yiyuanzi ZHAO
Journal of Chinese Physician 2024;26(2):172-175
Objective:To explore the correlation between the ratio of C-reactive protein (CRP) to albumin (CAR) and the syndrome type of Wei-Qi-Ying-Xue in patients with severe coronavirus disease 2019 (COVID-19).Methods:A case-control study was conducted to select 63 severe patients with COVID-19 admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from December 2022 to December 2023, including 50 severe cases and 13 critical cases. The clinical data of the patients were collected. According to the syndrome differentiation of Wei-Qi-Ying-Xue, there were 21 cases of Qi syndrome, 20 cases of Ying syndrome and 22 cases of Xue syndrome. The differences of CRP, ALB and CAR levels in patients with different Wei-Qi-Ying-Xue syndromes were compared. Spearman correlation test was used to test the correlation between CRP, ALB, CAR and the Wei-Qi-Ying-Xue syndrome type, and the receiver operating characteristic (ROC) curve was used to detect the diagnostic efficacy of CRP, ALB and CAR on the Wei-Qi-Ying-Xue syndrome type.Results:There was a statistically significant difference in the clinical classification of Western medicine among the three groups ( P<0.05). The CAR of the Ying group and the Xue group was higher than that of the Qi group ( P<0.05), while there was no statistically significant difference in age and comorbidities (all P>0.05). The CRP of the Xue group was higher than that of the Qi group ( P<0.05), and the ALB of the Ying group and the Xue group was lower than that of the Qi group (all P<0.05). Correlation analysis showed that there was a correlation between the Wei-Qi-Ying-Xue syndrome type and CRP, ALB and CAR ( P<0.05), among which CAR changed most significantly with the change of Wei-Qi-Ying-Xue syndrome type. ROC curve analysis showed that CRP, ALB and CAR had good diagnostic value for Qi syndrome and Xue syndrome ( P<0.05). The critical values of the diagnosis of Qi syndrome were 48.57 mg/L, 34.20 g/L and 2.97. The critical values of the diagnosis of Xue syndrome were 28.30 mg/L, 26.6 g/L and 5.96. Conclusions:CAR ratio is correlated with the Wei-Qi-Ying-Xue syndrome type of severe COVID-19 patients, and its level changes are in line with the evolution law of Wei-Qi-Ying-Xue syndrome. CAR≤2.97 is contributed to the diagnosis of Qi syndrome, and CAR>5.96 is contributed to the diagnosis of Xue syndrome. CAR may be an objective index related to the Wei-Qi-Ying-Xue syndrome type of severe COVID-19 patients.
7.The experimental study of X-ray diagnosis of closed reduction rotational displacement of femoral neck fractures
Xinlong MA ; Jianxiong MA ; Bin LU ; Fei LI ; Haohao BAI ; Ying WANG ; Aixian TIAN ; Lei SUN ; Yan WANG ; Benchao DONG ; Hongzhen JIN ; Yan LI ; Jiahui CHEN
Chinese Journal of Orthopaedics 2024;44(2):105-113
Objective:To explore the optimal index of rotational displacement of femoral neck fractures by modeling the axial rotational displacement of femoral neck fractures after reduction and based on X-ray projections.Methods:Six dry human femur specimens, comprising 2 males and 4 females, were utilized in the study. Design and manufacture a proximal femur ortholateral and oblique X-ray casting jigs and mounts. The femoral neck fracture was modeled on the femoral specimen, with Pauwells 30°, 50°, and 70° models (2 each) made according to Pauwells typing. The fractures were manually repositioned with residual anterior 20°, 40° and 60° axial rotational displacements. Each fracture model was projected at different angles (pedicled 40°, pedicled 20°, vertical 0°, cephalad 20°, and cephalad 40°), and the trabecular angle and Garden's alignment index of the model were measured to observe the imaging characteristics of the fracture line on the medial oblique and lateral oblique radiographs.Results:In the presence of a 20° and 40° anterior rotational displacement following reduction of a femoral neck fracture, the trabecular angle in the rotationally displaced group was not significantly different from that of the anatomically repositioned group in various projection positions. However, when a residual rotational displacement of 60° was present, the trabeculae appeared blurred at most projection angles in the Pauwells 30° and 50° models, failing to measure trabecular angles. In the Pauwells 70° fracture model, the trabecular angle in the rotational displacement group was significantly different from that in the anatomical reduction group. In anteroposterior radiographs, when the anterior rotation displacement was 60° in the Pauwells 70° group, Garden's contralateral index showed an unsatisfactory restoration (150°, 142°), whereas all rotationally displaced models in the Pauwells 30° and Pauwells 50° groups had a Garden's contralateral index of >155°, which achieved an acceptable restoration. In lateral radiographs, all rotational displacement models with Garden's alignment index>180° failed to achieve acceptable repositioning, and the larger the Pauwells angle the greater the Garden's alignment index at the same rotational displacement. In the internal oblique position with a bias towards the foot side, the image showed partial overlap between the femoral head and the shaft, making it difficult to assess the quality of the reduction. Conversely, when projected cephalad, the femoral neck appeared longer, particularly at a projection angle of 40° cephalad, allowing for clear observation of the fracture line and the anatomy of the proximal femur. The trabeculae were not well visualized in the external oblique position.Conclusion:There are limitations in applying the trabecular angle to assess the axial rotational displacement of the femoral head after reduction of femoral neck fractures. The Pauwells 70° with residual rotational anterior displacement of 60° was the only way to detect axial rotational displacement of the femoral head on anteroposterior radiographs Garden's alignment index. For the determination of axial rotational displacement of the femoral head, the Garden's alignment index on lateral radiographs provides higher reliability.
8.Advances in the use of stem cell mechanical sensitivity against osteoporosis
Liyun ZHOU ; Yan WANG ; Benchao DONG ; Peichuan YANG ; Jiahui SHEN ; Jianxiong MA ; Xinlong MA
Tianjin Medical Journal 2024;52(8):877-882
Osteoporosis is an emerging threat characterized by systemic damage to bone mass and microarchitecture leading to fragility fractures.Exosomes are nanosized vesicular particles secreted by cells into the extracellular compartment with biological activities similar to those of their cell of origin and play an important role in intercellular communication processes.Exosomes from multiple cell sources are involved in the regulation of bone-related cell proliferation and differentiation during bone metabolism,and have the advantages of high stability,non-immunogenicity and strong targeting ability,which make up for the shortcomings of traditional drug and stem cell therapies.Exosomes secreted from bone marrow mesenchymal stem cells(MSCs)can promote bone regeneration and improve morphology,biomechanics and histological damage,and exosomes derived from bone marrow mesenchymal stem cells(BMSCs)in the mechanical microenvironment are more effective in inducing osteogenesis,significantly enhancing the osteogenic effect of BMSCs and promoting bone regeneration.Therefore,this article provides a review on the mechano-sensitivity of MSCs,mechanical responsive functionalized exosomes of MSCs,and explores their potential role in the treatment of osteoporosis.
9.Clinical features and disease outcomes of patients with fundus lesions associated with novel coronavirus infection
Shasha WANG ; Qiuming LI ; Yongwei ZHOU ; Jiahui WU ; Lixin MA ; Shuqian DONG
Chinese Journal of Experimental Ophthalmology 2024;42(11):1028-1035
Objective:To observe the clinical features and disease outcomes of patients with fundus lesions associated with novel coronavirus infection (COVID-19).Methods:A case series observational study was conducted.Eighteen eyes of 10 patients with COVID-19 related fundus lesions diagnosed in the First Affiliated Hospital of Zhengzhou University from December 2022 to February 2023 were included.The affected eyes were examined by best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, scanning laser fundus photography (SLO), infrared fundus photography, optical coherence tomography (OCT), visual field and microperimetry.After the diagnosis was confirmed, according to the patients' willingness, 6 patients were treated with mecobalamin, vinblastine, and Aescuven forte orally.The other 4 patients were treated with glucocorticoid and methylprednisolone tablets orally with an initial dose of 32 mg/d, and the dose was reduced by 4 mg every 5 days, and potassium chloride tablets, calcium carbonate tablets, and omeprazole enteric-coated capsules were taken orally.According to the diagnosis and treatment of acute macular neuroretinopathy (AMN), the patients were divided into glucocorticoid treatment group (4 cases, 7 eyes) and non-glucocorticoid treatment group (4 cases, 8 eyes).The patients were followed up for 4 weeks.The BCVA, retinal morphology and structure, retinal sensitivity and fixation stability were compared before and after treatment.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-1482-002).Written informed consent was obtained from each subject.Results:Among the enrolled 10 cases (18 eyes), there were 9 cases (17 eyes) of AMN, including 1 eye with Purtscher-like retinopathy (PLR), 1 eye with acute para-central medial maculopathy (PAMM), and 1 eye with multiple transient white dot syndrome (MEWDS).The SLO images of AMN patients showed redbrown irregular lesions in the fovea or parafovea of the macular area.The OCT images showed patchy strong reflection between the OPL and ONL in the fovea or parafovea of the macular area, and the adjacent EZ/IZ had different degrees of local fracture, and the reflection signal was disordered.The BCVA of the eyes after 4 weeks of treatment was higher than that before treatment, and the difference was statistically significant ( Z=-2.823, P<0.05).After 4 weeks of treatment, the retinal sensitivity of the eyes was (26.57±2.24)dB, which was significantly higher than that before treatment (24.17±2.73)dB ( t=-11.329, P<0.001).There was no statistically significant difference in LogMAR BCVA and retinal sensitivity between the AMN glucocorticoid treatment group and the AMN non-glucocorticoid treatment group before and after 4 weeks of treatment ( Z=-0.986, P>0.05; t=-1.656, P>0.05). Conclusions:The main manifestations of COVID-19 related fundus lesions are AMN, PAMM, PLR, MEWDS, etc.OCT, microperimetry and other auxiliary examinations can help to diagnose the disease.The visual impairment and fundus structural changes caused by COVID-19 gradually improve after 4 weeks of treatment.
10.Effects of moderate-altitude exposure on intestinal flora of Chinese healthy population
Yaoliang ZHOU ; Jingyan ZHOU ; Jiahui MA ; Xin QI ; Yonghui MA ; Xiaoyan GAO ; Yanqun FAN ; Zhipeng LIU ; Xin LI
Chinese Journal of Pathophysiology 2024;40(11):2124-2134
AIM:To explore the effects of moderate-altitude exposure on intestinal flora in healthy individuals.METHODS:The aid-Tibet cadres,who were sent to work from Guangdong(average altitude<50 m)to Nyingchi(average altitude of 2 900 m),were recruited.A total of 76 samples were collected,including 42 samples from healthy adults with plateau living for 0 day and 34 samples from healthy adults with plateau living for 6 months.Fecal samples DNA were ex-tracted,sequenced by the 16S rDNA high-throughput sequencing technology and analyzed bioinformatically.RESULTS:Compared with the base group,α diversity was increased(P=4.00×10-4)and β diversity was decreased(P=1.00×10-3).After moderate altitude exposure,the relative abundance of phylum Proteobacteria(|LDA|>4,P<0.05),genus Escherich-ia-Shigella,species Enterococcus_faecalis,Haemophilus_influenzae and Helicobacter_sp._UNSW1.7sp decreased(adjust-ed P<0.05),wheras the relative abundance of phylum Bacteroidetes(|LDA|>4,P<0.05),genus Butyricimona,species Lactobacillus_sp._RA2113(s)and Butyricimonas_sp._Marseille-P2440(s)increased(adjusted P<0.05).The function-al prediction by PICRUSt showed a decrease in the relative abundance of pathway related to xenobiotics biodegradation and metabolism,membrane transport and amino acid metabolism(adjusted P<0.05).Conversely,the relative abundance of pathway related to biosynthesis of other secondary metabolites and nucleotide metabolism was increased(adjusted P<0.05).Finally,the results of microbiome phenotype prediction by BugBase showed that moderate altitude exposure im-proves the gut microbiota functions involving anaerobic oxygen tolerance and gram positive(adjusted P<0.05).And bacte-ria containing facultatively anaerobic oxygen tolerance,oxidative stress tolerance,gram negative and biofilm formation in the six-group decreased significantly compared with those in base group(adjusted P<0.05).CONCLUSION:Moderate altitude exposure impacts the diversity,abundance and function of intestinal flora in healthy population,suggesting that al-titude factors may have some influence on gut microbiota.


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