1.Fufang Kangjiaolv Capsules Treat Anxiety in Rat Model of Chronic Restraint Stress via Microbiota-gut-brain Axis
Wenxin FAN ; Tingyue JIANG ; Yu WANG ; Ge ZHANG ; Yifan LU ; Mengmeng LIU ; Jiayuan LI ; Renzhi MA ; Jinli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):95-107
ObjectiveTo observe the intervention effect of Fufang Kangjiaolv capsules on anxiety-like behaviors in the rat model of chronic restraint stress (CRS) and explore the mechanism underlying the anti-anxiety effect via the microbiota-gut-brain axis. MethodsRats were assigned into blank, model, positive drug (diazepam, 1 mg·kg-1), and low-, medium-, and high-dose (0.75, 1.5, 3 g·kg-1, respectively) Fufang Kangjiaolv capsules groups. After 14 days of administration, the elevated plus maze test, open field test, light and dark box test, and marble burying test were performed. Hematoxylin-eosin staining was employed to observe the pathological changes in the hippocampus and colon of rats, and Nissl staining was conducted to observe the damage of hippocampal neurons. The gut microbiota was analyzed by 16S rRNA gene sequencing. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of zonula occludens-1 (ZO-1) and occludin in the colon of rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the colon, serum, and hippocampus were determined by enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of ZO-1, occludin, nuclear factor-κB p65 (NF-κB p65) in the colon tissue and NF-κB p65 and brain-derived neurotrophic factor (BDNF) in the hippocampal tissue. ResultsCompared with the blank group, the model group showed reductions in the time and frequency ratio of rats entering the elevated plus maze, the time and frequency of rats entering the central area of the open field, the time of entering the open box, the times of passing through the light and dark box, and the number of unburied beads (P<0.05, P<0.01). Compared with the model group, Fufang Kangjiaolv capsules ameliorated the anxiety of the model rats to varying degrees, and the high-dose group had the best effect, with increases in the proportions of time and frequency of rats entering the open arm in the elevated plus maze (P<0.05), the number of rats entering the central area in the open field (P<0.05), the time of entering the open box, the times of passing through the light and dark boxes, and the number of unburied beads (P<0.01). Moreover, the high-dose group showed alleviated pathological damage of hippocampal neurons and colon. The results of 16S rRNA gene sequencing showed that the model group had increased relative abundance of Firmicutes, Deferribacterota, Romboutsia, and Phascolarctobacterium, while it had decreased relative abundance of Bavcteroidota and Lactobacillus. The drug administration groups showed increased relative abundance of Bavcteroidota, Bacteroides, norank f norank o Clostridia UCG-014, and Blautia and decreased relative abundance of Firmicutes and Deferribacterota. Compared with the blank group, the model group showed down-regulated protein and mRNA levels of ZO-1 and occludin in the colon (P<0.01), elevated levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated protein level of NF-κB p65 in the colon and hippocampus (P<0.01), and down-regulated protein level of BDNF in the hippocampus (P<0.05). Compared with the model group, high-dose Fufang Kangjiaolv capsules up-regulated the mRNA levels of ZO-1 and occludin in the colon (P<0.01), lowered the levels of TNF-α, IL-6, and IL-β in the colon, serum, and hippocampus (P<0.01), up-regulated the protein levels of ZO-1 (P<0.01) and occludin (P<0.05) in the colon, down-regulated the protein level of NF-κB p65 in the colon and hippocampus (P<0.05), and up-regulated the protein level of BDNF in the hippocampus. ConclusionFufang Kangjiaolv capsules can reduce the anxiety-like behaviors in the rat model of CRS by regulating the gut microbiota disturbance, up-regulating the expression of tight junction proteins in the colon, repairing intestinal mucosal mechanical barrier, and down-regulating NF-κB/BDNF signaling pathway, thereby reducing peripheral and central inflammation. This study proves the hypothesis that Fufang Kangjiaolv capsules play an anti-anxiety role via the microbiota-gut-brain axis, providing a new idea for further research.
2.Effect of Qingxin Jieyu Granules Regulating Mitophagy on Ventricular Remodeling After Myocardial Infarction of C57B/L6 Mice
Yifan CHEN ; Jianfeng CHU ; Zhonghui JIANG ; Zhuye GAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):70-78
ObjectiveTo explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction, and their regulatory role in mitophagy. MethodsSixty male C57BL/6 mice were randomly assigned to six groups: sham-operated group, model group, Qingxin Jieyu granules low-, medium-, and high-dose groups (1.3, 2.6, 5.2 g·kg-1), and sacubitril valsartan sodium group (0.03 g·kg-1), with 10 mice per group. Except for the sham-operated group, all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model. Ultrasound was used to measure left ventricular parameters, including end-diastolic and end-systolic diameters (LVIDd, LVIDs), diastolic and systolic posterior wall thickness (LVPWd, LVPWs), end-diastolic and end-systolic volumes (LV Vold, LV Vols), left ventricular ejection fraction (LVEF), and fractional shortening (LVFS). Additionally, the heart mass index and heart weight/tibia length ratio of mice were calculated. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify brain natriuretic peptide (BNP), creatine kinase isoenzyme (CK-MB), angiotensinⅡ (AngⅡ), and lactate dehydrogenase (LDH) levels in the serum of mice. Histological analysis using hematoxylin-eosin (HE) and Masson staining was conducted to examine morphological changes in myocardial tissue. Immunohistochemistry assessed the expression of vascular growth factors, including basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice. Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK) and phosphorylated mammalian target of rapamycin (p-mTOR) proteins in myocardial tissue from each experimental group. ResultsCompared to the sham-operated group, the model group mice exhibited significantly elevated levels of LV Vold, LV Vols, LVIDd, LVIDs, cardiac mass index, heart weight/tibia length ratio, BNP, LDH, and p-mTOR protein expression (P<0.05), along with decreased levels of LVPWd, LVPWs, LVEF, LVFS, and p-AMPK protein expression (P<0.05). The model group also displayed substantial inflammatory cell infiltration, collagen deposition in myocardial cells, reduced expression of bFGF and VEGF, mitochondrial swelling, and cristae fragmentation. Compared to the model group, the sacubitril/valsartan group and mid-dose Qingxin Jieyu granules group showed significant reductions in LVIDs, LV Vold, LV Vols, BNP, CK-MB, LDH, and p-mTOR protein expression (P<0.05), coupled with increases in LVEF, LVFS, and p-AMPK expression (P<0.05). Improvements were observed across all treatment groups, including reduced inflammatory cell infiltration and collagen deposition, increased bFGF and VEGF expression, alleviated mitochondrial swelling, and the presence of autophagosomes and lysosomes
3.Application of Eurorad database in the teaching of radiology in standardized residency training: A case study of teaching film-reading
Jingyu ZHONG ; Qinhua MIN ; Caisong ZHU ; Zhenmin JIANG ; Yifan WANG ; Huan ZHANG ; Weiwu YAO
Chinese Journal of Medical Education Research 2024;23(1):134-139
The teaching of radiology in standardized residency training needs a large number of case data to strengthen the subjective understanding and awareness of residents. The database built by residency training bases can meet the needs of teaching to a certain extent, but the conditions of training bases vary across regions, which makes it difficult to achieve homogeneity in the teaching of radiology. This article discusses the application of Eurorad database in the teaching of radiology in standardized residency training. This database is free of charge, reliable, and comprehensive and provides a large number of free reliable cases and images for teaching, covering both common and rare diseases. Moreover, it can also be used to cultivate the English ability and comprehensive quality of residents and help to establish a hierarchical training system for radiology and non-radiology residents, thereby promoting the improvement in the quality of standardized residency training. This article shows the potential value of Eurorad database in the teaching of radiology in standardized residency training, and comparative studies are needed in the future to further prove its effectiveness.
4.Discussion on the Pathogenic Mechanism and Treatment of Post-Myocardial Infarction Ventricular Remodeling Based on the Theory of "Yang Transforms into Qi,While Yin Constitutes Form"
Yifan CHEN ; Zhonghui JIANG ; Liuding WANG ; Dan MA ; Zhuye GAO
Journal of Traditional Chinese Medicine 2024;65(17):1762-1768
Ventricular remodeling is a crucial pathological process in the prognosis and regression of myocardial infarction. Guided by the theory of “yang transforms into qi, while yin constitutes form" of The Inner Canon of Yellow Emperor (《黄帝内经》), combined with the pathological characteristics and manifestations of ventricular remodelling, it is believed that insufficient "yang transforms into qi" and excess "yin constitutes form" resulting to heart yang deficiency and turbid pathogen obstruction are the basic pathomechanism of ventricular remodelling after myocardial infarction; insufficient "yin constitutes form" and excess "yang transforms into qi" resulting to inadequate nourishment of the heart meridians and the emergence of various pathological changes are the key pathomechanism of prognosis and regression. Combined with clinical practice, we advocated that harmonizing yin and yang to maintain the dynamic balance of "yang transforms into qi" and "yin constitutes form". We also proposed the use of warming and tonifying to harmonise qi and transform it to help yang transport; resolving phlegm and removing dampness, invigorating blood and resolving toxins to disperse yin accumulation; clearing heat and extinguishing wind, and nourishing yin and channels to improve the prognosis. All these findings and summary could provide ideas on traditional Chinese medicine for prevention and treatment of ventricular remodelling after myocardial infarction.
5.Quercetin ameliorates diabetic kidney injury in rats by inhibiting the HMGB1/RAGE/NF-κB signaling pathway
Yifan JIANG ; Xiaorong LI ; Jiayi GENG ; Yongfeng CHEN ; Bi TANG ; Pinfang KANG
Journal of Southern Medical University 2024;44(9):1769-1775
Objective To explore the effect of quercetin on renal inflammation and cell apoptosis in diabetic rats and its possible mechanisms.Methods Twenty-four adult male SD rats were randomized equally into normal control group,high-glucose and high-fat feeding group,streptozotocin(STZ)-induced diabetic model group,and quercetin treatment(daily dose 100 mg/kg)group.Pathological changes of the renal tissues of the rats were observed with HE staining,serum inflammatory factor levels were determined with ELISA,and renal expression of NF-κB was observed by immunohistochemistry.Fast blood glucose(FBG),serum levels of triglyceride(TG),BUN,and Scr,and 24-h urine protein content of the rats were measured,and renal expressions of HMGB1,RAGE,NF-κB,Bax,Bcl-2,and caspase-3 were detected with Western blotting.Results The diabetic rats showed significantly increased levels of FBG,TG,BUN,and Scr,renal hypertrophy index,24-h urinary protein content,serum IL-1β,IL-6 and TNF-α levels and renal expressions HMGB1,RAGE,NF-κB,Bax,and caspase-3 with decreased renal expression of Bcl-2.All these changes were significantly alleviated by quercetin treatment of the rats.Conclusion Quercetin can ameliorate kidney injury in diabetic rats possibly by inhibiting the HMGB1/RAGE/NF-κB inflammatory signaling pathway to reduce renal inflammation and renal cell apoptosis.
6.Effectiveness of bone plate reduction combined with resorbable plate fixation in the treatment of large mandibu-lar cysts
Yifan HU ; Qingyan SUN ; Chenyi WANG ; Xiaoting ZHAI ; Hua JIANG ; Huawei LIU
West China Journal of Stomatology 2024;42(4):470-475
Objective This study aims to observe the clinical effect of bone plate reduction in combination with a re-sorbable plate on large mandibular cysts.Methods Between October 2017 and September 2022,patients with large mandibular cysts in the presence of labial and buccal cortical bone were involved in the study.Intraoral approach was performed for bone plate reduction.Cone beam computed tomography(CBCT)scan was reviewed at 3,6,and 9 months postoperatively to observe postoperative complications.Osteogenic results were assessed at these times to determine the clinical outcomes of this procedure.Results Eleven cases with large mandibular cysts in the presence of cortical bone were evaluated.The average thickness of the cortical bone on the labial and buccal sides was measured to be about(1.98±0.37)mm before surgery,with a mean value of(0.73±0.17)mm at the thinnest part of the plate and up to 0.51 mm at the thinnest part of the plate.The cystic cavities were well re-vealed during the surgeries,which were completed suc-cessfully.Postoperatively,the wounds healed in one stage without infection.The percentages of cyst shrinkage were 20.01%,41.76%,and 73.41%at 3,6,and 9 months after surgery,respectively.Quantitative measurement of bone mineral density in the jaws by CBCT with MIMICS software.The bone mineral densities of the adult bone were 313.78,555.85,and 657.45 HU at the 3,6,and 9 month time intervals,respectively.No significant change in the patient's maxillofacial appearance were observed from the preoperative period as assessed by the patient's and observer's visual analog scale.Conclusion Bone plate reduction is an effective treatment for large mandibular cysts of the oral and maxillofacial re-gion with the presence of cortical bone.
7.Mid-to-long term fate of neo-aortic root after arterial switch operation for Taussig-Bing anomaly: A retrospective study in a single center
Mingjun GU ; Dian CHEN ; Renjie HU ; Jie HU ; Wei DONG ; Wen ZHANG ; Qi JIANG ; Yifan ZHU ; Haibo ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(04):504-509
Objective To explore growth pattern of neo-aortic root as well as development of neo-aortic regurgitation after arterial switch operation (ASO) for Taussig-Bing anomaly. Methods From 2002 to 2017, the patients who received ASO, and were discharged alive from Shanghai Children’s Medical Center and followed up for more than 3 years were retrospectively involved in this study. Results A total of 127 patients were enrolled. There were 98 (77.2%) males, the median age at ASO was 73.0 d and the average weight was 4.7 kg. Forty-five (35.4%) children were complicated with mild or mild-to-moderate pulmonary insufficiency (PI) before ASO. The average follow-up time was 7.0 years. During the follow-up, 14 (11.0%) children presented moderate or greater neo-aortic regurgitation (neo-AR). The diameter of neo-aortic annulus and sinus of Valsalva was beyond normal range during the entire follow-up. The average diameter of neo-aortic annulus was 18.0 mm at 5 years and 20.5 mm at 10 years. The average diameter of sinus of Valsalva was 25.9 mm at 5 years and 31.1 mm at 10 years. Neo-AR continued to develop over time. The diameter of children who developed moderate or greater neo-AR was constantly larger than that of children who did not (χ2=18.3, P<0.001). Preoperative mild or mild-to-moderate PI was an independent risk factor for the development of moderate or greater neo-AR during mid-to-long term follow-up (c-HR=3.46, P=0.03). Conclusion The diameters of neo-aortic annulus and sinus of Valsalva of Taussig-Bing children who receive ASO repair continue to expand without normalization. The dilation of annulus correlates with the development of neo-AR. PI before ASO repair increases the risk of neo-AR development.
8.Development and validation of a prognostic scoring system for colorectal cancer patients with Hepato-bone metastasis:a retrospective study
Le QIN ; Yixin HENG ; Jiaxin XU ; Ning HUANG ; Shenghe DENG ; Junnan GU ; Fuwei MAO ; Yifan XUE ; Zhenxing JIANG ; Jun WANG ; Denglong CHENG ; Yinghao CAO ; Kailin CAI
Journal of Clinical Surgery 2024;32(9):947-954
Objective To establish a nomogram model for efficiently predicting overall survival(OS)and cancer-specific survival(CSS)in patients with CRCHBM.Method 2239 patients from 2010 to 2019 were retrospectively analyzed from the Surveillance,Epidemiology,and End Results Program(SEER)databases and Wuhan Union Hospital Cancer Center.SEER is randomly assigned to the training and internal validation cohorts,and the Wuhan database serves as the external validation.Cox regression analyses were used to determine the independent clinicopathological prognosis factors affecting OS and CSS,and a nomogram was constructed to predict OS and CSS.The clinical utility of columnar plots was assessed using calibration curves,area under the curve(AUC),and decision curve analysis(DCA).Result OS column line graphs were constructed based on nine independent predictors:age,tumor location,degree of differentiation,tumor size,TNM stage,chemotherapy,primary focus surgery,number of lymph nodes sampled,and serum carcinoembryonic antigen(CEA)level.The C-index of the nomogram to predict the 1-,3-,and 5-year OS were 0.764,0.790,and 0.805 in the training group,0.754,0.760,and 0.801 in the internal validation group,and 0.822,0.874,and 0.906 in the external validation group.CSS column line graphs were constructed based on 3 independent predictors of TNM staging,radiotherapy and chemotherapy.The 1-,3-,and 5-year CSS AUROC values of the training group were 0.791,0.757,and 0.782,respectively.0.682,0.709,0.625 in the internal validation group and 0.759,0.702,0.755 in the external validation group,respectively.The results of receiver operating characteristic curve(ROC),ROC and DCA showed that the use of our model was more effective in predicting OS and CSS than other single clinicopathological features.Conclusion In summary,the nomogram based on significant clinicopathological features can be conveniently used to predict OS and CSS individually in patients with CRCHBM.
9.Clinicopathological features of 5 cases of non-small cell lung cancer with SMARCA4 deficient
Jing ZHAO ; Yifan LU ; Tao JIANG ; Danting XIONG ; Shijie YU ; Liufang YANG ; Jiwei ZHANG ; Wenjuan GAN
Chinese Journal of Clinical and Experimental Pathology 2024;40(5):515-519
Purpose To investigate the clinical pathologic features of five SMARCA4-deficient non-small lung cancers(SMARCA4-dNSCLCs).Methods Five cases of SMARCA4-dNSCLC was underwent by HE,immunohistochemical staining,and molecular detection,analyzed their clinicopathological char-acteristics and reviewed relevant literatures.Results All 5 ca-ses were male,and mean age was 66 years.Five patients had a history of smoking,three patients were treated with cough and blood in sputum as the first symptom,one was treated with a history of pulmonary tuberculosis combined with limb mobility disorder,and one was diagnosed with pulmonary nodules by physical examination.Under microscopic observation,tumor cells were poorly differentiated,with solid nest sheet distribu-tion,some with glandular structure,tumor cells had abundant e-osinophilic or transparent cytoplasm,vacuolar nuclear chroma-tin,nucleoli was visible,and nuclear mitosis was common.In-flammatory cell infiltration and sheet of necrosis were seen in the stroma.Immunohistochemical staining showed 5/5 diffuse ex-pression of CK(AE1/AE3)and CK7,5/5 loss expression of BRG1,1/5 diffuse expression of p40 and CK5/6,and Ki67 proliferating index ranged from 20%to 90%.FISH tests showed that 4/4 SMARCA4 genes missed.Five patients were followed up for 2-15 months,3 patients died and 2 patients survived.Conclusions SMARCA4-dNSCLC can have extensive morphologi-cal features,high degree of malignancy,and complicated treat-ment.BRG1 deficiency is helpful for diagnosis.Deepening the understanding of SMARCA4-dNSCLC can help the clinical cor-rect choice of treatment strategies and accurately evaluate patient prognosis.
10.Synthesis of fibroblast activation protein-induced intracellular self-assembly Gd-nanoparticle contrast agent and study of MR imaging
Xiangyuan Guo ; Yifan Zheng ; Manlin Zhang ; Yibo Ren ; Jinhui Jiang
Acta Universitatis Medicinalis Anhui 2024;59(12):2087-2094
Objective:
To synthesis a Gd-labeled molecular probe capable of responding to fibroblast activation protein(FAP) highly expressed in tumor-associated fibroblasts for magnetic resonance imaging studies of pancreatic cancer.
Methods:
The chemical structure of Z-Gly-Pro-Cys-Lys(Gd-DOTA)-CBT(contrast agent 1) was characterized through mass spectrometry analysis.High-performance liquid chromatography(HPLC) was used to verify the contrast agent 1 formed a dimer under the cleavage of fibroblast activation protease(FAP) in vitro,and further self-assembled to form Gd-nanoparticles.The cell counting Kit-8(CCK-8) assay was used for biological safety analysis.BxPc-3 tumor-bearing mice were established and randomly divided into three groups,3 mice intravenously(i.v.) injected with 0.08 mmol/kg contrast agent 1 through tail vein were designated as the experimental group,3mice i.v.injected with 0.08 mmol/kg Gd-DTPA were designated as the control group,and 3 mice i.v.injected with normal saline were designated as the blank control group(n=3).Dynamic MR scanning from 0 to 3 hours was performed for them,respectively.The enhancement effects of T1-and T2-weighted imaging were observed and the rate of change in the tumor-to-muscle ratio(T/M) over time was analyzed.
Results:
Contrast agent 1 efficiently responded to FAP in vitro,forming dimers under the action of FAP,and further self-assembled to form nanoparticle structures.Contrast agent 1 has good biocompatibility.The BxPc-3 tumor-bearing mice showed that the T1-weighted contrast of the tumor reached its highest level at 2 h post injection of contrast agent 1 or Gd-DTPA.In T1-weighted imaging,the T/M at 2 h in the experimental group was 135.20%±0.06% of 0 h,the T/M at 2 h in the Gd-DTPA group was 115.70%±0.05% of 0 h and the T/M at 2 h in the saline group was 113.5%±0.02% of 0h.Compared with Gd-DTPA control group,the experimental group had significantly enhanced T1-weighted MR contrast,and the difference was statistically significant(P<0.01).In tumor T2-weighted imaging,the T/M quantitative analysis showed that the tumor T2-weighted contrast enhancement of the three groups was relatively small,and the T/M of the experimental group and the control group at 0.5 h was 94.60±0.03% and 106.30±0.04% of the 0 h,respectively.In the normal saline group,T/M at 0.5 h was 102.20±0.002% of that at 0 h,and no significant enhancement of the T2-weighted MR contrast of tumor was observed.
Conclusion
Successfully construct a FAP-responsive molecular probe which can self-assemble to form a Gd-nanoparticle structure in tumor cells under the cleavage of FAP,effectively improving the enrichment of Gd in the target region,and enhancing T1-weighted magnetic resonance imaging of pancreatic cancer,which has potential clinical application value.


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