1.Mechanism of Icariin in Regulating TGF-β1/Smad Pathway to Induce Autophagy in Human Bone Microvascular Endothelial Cells
Yaqi ZHANG ; Yankun JIANG ; Guoyuan SUN ; Bo LI ; Ran DING ; Cheng HUANG ; Weiguo WANG ; Qidong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):123-130
ObjectiveTo investigate the regulatory effect of icariin (ICA) on transforming growth factor-β1 (TGF-β1)/Smad pathway in bone microvascular endothelial cells (BMECs) and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured, and the cell types were identified by immunofluorescence. Cells were divided into the control group, model group (0.1 g·L-1 methyl prednisolone), ICA group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA), and TGF-β inhibitor group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA +1×10-5 mol·L-1 LY2157299). Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β1/ Smad pathway. ResultsAfter cell separation culture, platelet endothelial cell adhesion molecule (CD31) and von willebrand factor (vWF) immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged, and the nucleus was pyknotic and broken in the model group. Compared with the model group, the ICA group had complete cell membranes, clear structures, with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes, and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group, in the model group and the LY2157299 group, autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group, the mRNA and protein expressions of autophagy effector protein 1 (Beclin1) and microtubule-associated protein 1 light chain 3B (LC3B) in the model group were significantly decreased (P<0.01), and those of ubiquitin-binding protein (p62) were significantly increased (P<0.01). The mRNA expression of TGF-β1, Smad homolog 2 (Smad2), and Smad homolog 3 (Smad3) decreased (P<0.05, P<0.01). The protein expressions of TGF-β1, p-Smad2, and p-Smad3 were significantly decreased (P<0.01). Compared with those of the model group, the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased (P<0.01), and those of p62 significantly reduced (P<0.01). The mRNA expression of TGF-β1, Smad2, and Smad3 increased significantly (P<0.01). The protein expression of TGF-β1, p-Smad2, and p-Smad3 increased significantly (P<0.01). Compared with those in the model group, the mRNA and protein expressions of Beclin1, LC3B, and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β1 pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs, and its mechanism may be related to activating the TGF-β1/Smad signaling pathway.
2.Mechanism of Traditional Chinese Medicine in Treating Steroid-Induced Osteonecrosis of Femoral Head via Regulating PI3K/Akt Pathway: A Review
Yaqi ZHANG ; Bo LI ; Jiancheng TANG ; Ran DING ; Cheng HUANG ; Yaping XU ; Qidong ZHANG ; Weiguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):141-149
Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells, necrosis, and trabecular fractures, SONFH is accompanied by pain, femoral head collapse, and joint dysfunction, which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis, bone microvascular endothelial cell (BMEC) apoptosis, oxidative stress, and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation, thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts, promoting angiogenesis in BMECs, and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine (TCM) has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway, as well as its regulatory effects on osteoblasts, mesenchymal stem cells, osteoclasts, BMECs, and other cells. Additionally, the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings, this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM, it is expected to bring safer and more effective treatment options for patients with SONFH.
3.Application value of venous excess ultrasound score (VExUS Score) in patients with sepsis complicated acute kidney injury
Wei DA ; Tiantian ZHU ; Xiaobo WANG ; Peipei LIANG ; Xiaodong XIE ; Rui CHEN ; Ran LI ; Zhenxing DING ; Hong ZHANG
Chinese Journal of Emergency Medicine 2024;33(3):312-316
Objective:To evaluate the effect of venous excess ultrasound score (VExUS Score) in the acute kidney injury(AKI) in Patients with sepsis, so as to reduce the risk of disease and improve the prognosis of patients.Methods:This experiment was a single-center prospective cohort study. Include septic patients with AKI who were admitted to the Department of Emergency Intensive Care Unit of the First Affiliated Hospital of Anhui Medical University from February 2022 to February 2023, Those with inadequate window, inferior vena cava (IVC) thrombus, age<18 years and known case of cirrhosis with portal hypertension were excluded from the study. Patients underwent ultrasound examination with serial determination till AKI resolved or patient is initiated on dialysis.Results:Totally 86 patients were enrolled for the study. The mean age was (60.43±15.48) with 50 (58.1%) males. Mean sequential organ failure assessment (SOFA) score was (6.23±1.87). 38 patients (44.2%) were in AKI stage 1, while 24 patients (27.9%) were in AKI stage 2 and stage 3 each. 52 patients (60.5%) had VExUS grade Ⅲ. Resolution of AKI injury showed significant correlation with improvement in VExUS grade ( p value 0.003). Similarly, there was significant association between changes in VExUS grade and fluid balance ( p value 0.005). There was no correlation between central venous pressure (CVP), left ventricular function, and right ventricular function with change in VExUS grade. Conclusions:The study shows a significant correlation between the VExUS Score and AKI staging, With improvement in kidney function, there is decline in the VExUS grade as well. Moreover VExUS Score might reliably demonstrate venous congestion and aid in the clinical decision to perform fluid removal.
4.Intervention effects of icariin combined with glucocorticoid in rats of steroid-resistant nephrotic syndrome
Can LIU ; En-Lai DAI ; Zhao-Ran DING ; Shu-Wen DUAN
The Chinese Journal of Clinical Pharmacology 2024;40(13):1913-1917
Objective To investigate the interventional effects of Icariin(IC A)combined with prednisone acetate tablets(PAT)in rats with steroid-resistant nephrotic syndrome(SRNS)model.Methods Male SD rats were used to construct the SRNS model with 2 injections of adriamycin(ADR),and were randomly divided into the model group,PAT group,ICA group,and the combined group,with 10 rats in each group after successful modeling;another 10 rats were taken as the blank group.The blank and model groups were given 0.9%NaCl;the PAT group was given 6.3 mg·kg-1·d-1 PAT;the ICA group was given 50 mg·kg-1·d-1 ICA;and the combined group was given 6.3 mg·kg-1·d-1 PAT+50 mg·kg-1·d-1 ICA.The volume of gavage of the five groups of rats was 1 mL·100 g-1,and the drug was administered once a day for 6 weeks.The renal function and blood lipid level of rats in each group were compared;the expression of calcium/calmodulin dependent protein kinase Ⅱ α(CaMK Ⅱα),cofilin-1 and F-actin were detected by Western blotting.Results Urinary protein quantification values at 8 weeks in blank,model,PAT,ICA and combined groups were(6.66±1.48),(178.38±8.96),(161.56±5.49),(157.13±8.32)and(96.90±5.05)mg·24 hi-1;serum creatinine levels were(30.90±1.79),(41.10±2.77),(34.90±2.03),(35.10±2.18)and(31.90±2.47)μmol·L-1;triglycerides levels were(0.87±0.14),(2.30±0.41),(1.94±0.44),(1.17±0.59)and(0.89±0.30)mmol·L-1;total cholesterol levels were(1.54±0.08),(2.53±0.22),(2.14±0.59),(2.27±0.31)and(1.93±0.32)mmol·L-1;the relative expression levels of CaMK Ⅱ α proteins were 0.88±0.09,0.65±0.06,0.71±0.08,0.76±0.07 and 0.88±0.08;the p-Cofilin-1/Cofilin-1 ratios were 0.56±0.27,2.52±0.04,0.75±0.02,0.91±0.20 and 0.53±0.05;the relative expression levels of F-actin protein were 0.93±0.01,0.64±0.01,0.75±0.02,0.80±0.01 and 0.85±0.00,respectively.The differences of the above indexes in the model group were statistically significant compared with those in the blank group and the combined group(all P<0.05).Conclusion ICA combined with PAT can improve renal function,lipid levels,improve renal histopathological structure,and promote skeletal protein remodeling in SRNS rats by regulating CaMK Ⅱ α/Cofilin-1/F-actin pathway.
5.Research status of the correlation between ferroptosis and renal fibrosis
Li-Juan LIANG ; En-Lai DAI ; Jun-Yuan BAI ; Can LIU ; Zhao-Ran DING ; Jie ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2278-2282
Renal fibrosis is a common pathological manifestation of all chronic kidney diseases.Ferroptosis is closely related to the pathogenesis of renal fibrosis and can influence the onset of renal fibrosis,and it is the most critical step in the development of renal fibrosis.The paper describes the relationship between ferroptosis and renal fibrosis,discusses the research progress of ferroptosis on renal fibrosis,and further summarizes,analyzes,and describes the effective and highly targeted natural active ingredients of traditional Chinese medicines against ferroptosis,and concludes that the reversal of renal fibrosis is achieved through the regulation of the key targets of ferroptosis,with a view to providing a broad new direction for its prospects in the field of renal fibrotic disease prevention and treatment;and to provide a scientific guide for clinical treatment and basis for clinical treatment.
6.Study on the Chinese medicine symptoms of kidney yang deficiency based on sickness behaviour in rats with adriamycin nephropathy
Zhao-Ran DING ; En-Lai DAI ; Wei-Wei HUANG ; Can LIU ; Shu-Wen DUAN ; Sen-Bing ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(20):3018-3022
Objective To study the common basis and association between sickness behaviour and occurrence of classical symptoms of kidney yang deficiency of rats with adriamycin nephropathy.Methods The SD rats were given adriamycin by tail-vein injection for 2 times(4.0 and 3.5 mg·kg-1,one week apart)to construct the model of nephrotic syndrome with Chinese medicine symptom of kidney yang deficiency.After successful modeling,the model rats were randomly divided into adriamycin group(ADR group),corticosterone group(CORT group)and hydrocortisone group(HYD group),with 12 rats per group;another 12 normal rats were taken as normal group.In the HYD group,25 mg·kg-1·d-1 HYD was administered for 14 d to establish kidney yang deficiency model with simple hypothalamus-pituitary-adrenal cortex(HPA)axis inhibition.CORT group was adding 25 μg·mL-1 corticosterone to the water for 6 weeks,and the others drinking water supplied.The levels of urinary 17-hydroxy steroid were measured by enzyme linked immunosorbent assay.Glucocorticoid receptor(GR)and nuclear factor-kappa B(NF-κB)protein expression levels in kidney and hypothalamus were detected by Western blotting.Results In the normal,ADR,CORT and HYD groups,the urinary 17-hydroxysteroid levels were(19.14±1.94),(10.07±1.62),(20.30±1.55)and(14.23±2.37)μg·L-1;the relative expression levels of GR protein in hypothalamic were 0.63±0.05,0.11±0.05,0.85±0.08 and 0.35±0.06;the relative expression levels of NF-κB protein in hypothalamic were 0.06±0.03,0.96±0.03,0.59±0.01 and 0.23±0.04;the relative expression levels of GR protein in kidney tissue were 0.94±0.06,0.06±0.02,0.40±0.02 and 0.09±0.08;the relative expression levels of NF-κB protein in kidney tissue were 0.07±0.05,0.81±0.12,0.72±0.07 and 0.49±0.08,respectively.Compared with the ADR and HYD groups,the above indexes in the normal group were statistically significant(P<0.05,P<0.01).And compared with the ADR group,the relative expression levels of NF-κB protein in renal tissue with CORT group were not statistically significant(P>0.05),but the other indexes in CORT group were statistically significant(all P<0.01).Conclusion HPA axis dysfunction with GR damaged and activated inflammatory levels are the common basis for the combination of typical symptoms of kidney yang deficiency and sickness behaviour which characterised by"deficiency and cold syndrome".
7.Advances and prospects of conversion surgery for unresectable esophageal squamous cell carcinoma
Xingqiang RAN ; Guidong SHI ; Yu ZHOU ; Hao YANG ; Hao DING ; Maoyong FU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(07):1050-1057
Esophageal squamous cell carcinoma can easily penetrate into the esophageal wall and invade adjacent organs due to the lack of serosa. Stage cT4b tumors involving organs adjacent to the aorta, vertebral body, trachea, or bronchus were considered unresectable. For unresectable esophageal squamous cell carcinoma, radical chemoradiotherapy or chemotherapy is recommended. However, the therapeutic effect is poor. With the advent of conversion surgery, surgical resection is feasible after induction therapy for patients with esophageal tumors that are initially unresectable due to adjacent organ invasion or distant metastasis. This article reviews the research on conversion surgery for unresectable esophageal squamous cell carcinoma in recent years in order to explore the clinical application prospects of conversion surgery.
8.Applications and Prospect of Diagnostic Radionuclide
Jiaxin DING ; Zhuoling RAN ; Yuxian ZHANG ; Ran ZHANG ; Lin YU ; Liping YANG ; Yuanqing NING ; Xu GAO ; Minghui AN ; Jing XIE ; Dong CHAI ; Jian GONG
Herald of Medicine 2024;43(10):1609-1614
Nuclear medicine plays an indispensable role in the diagnosis,treatment,and prognosis of a wide range of diseases.Nuclear medicine using radionuclides for diagnosis has the advantages of accuracy,speed,high sensitivity and high resolution.Currently,several radionuclides play pivotal roles in disease diagnosis.This article primarily examines the clinical application and research of diagnostic radionuclides,including 18 F,89 Zr,68 Ga,99m Tc,131 I,123 I,and 11 C.The objective is to offer valuable insights for disease diagnosis and staging of diseases.
9.Pharmacovigilance for Radiopharmaceuticals
Yue SUN ; Yuxuan ZHENG ; Zhenjiang ZHANG ; Yuxian ZHANG ; Ran ZHANG ; Chang LU ; Li ZHANG ; Ding LI ; Jiachen TU ; Jing XIE ; Huan ZHOU ; Jian GONG
Herald of Medicine 2024;43(10):1615-1619
Radiopharmaceuticals play an important role in the medical field,but they also carry certion risks and potential safety concerns.Medical institutions implement pharmacovigilance to ensure the safety of patients'drug use,including the safety of Radiopharmaceuticals.The operation and management of the pharmacovigilance system in the United States and the European Union are relatively mature.China can learn from their advanced concepts and establish our own radiopharmaciligence system.
10.AI-HIP system for prosthesis size,global femoral offset and osteotomy in total hip arthroplasty
Guo-Yuan SUN ; Yan-Kun JIANG ; Tong LI ; Xue-Feng CONG ; Cheng HUANG ; Ran DING ; Wei-Guo WANG ; Qi-Dong ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(9):848-854
Objective To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty(THA)and its influence on clinical outcomes.Methods A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system(AI-HIP group),including 16 males and 20 females,aged from 43 to 81 years old with an average of(62.2±10.9)years old.According to the matching principle,36 patients who were planned by the traditional template method at the same period were selected as the control group,including 16 males and 20 females,aged from 40 to 80 years old with an average of(60.9±12.1)years old.The accuracy between two groups of prostheses were compared,as well as the combined eccentricity difference between preoperative planning and postoperative practice,lower limb length difference,osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect.Harris score and visual analogue scale(VAS)were used to evaluate clinical efficacy.Results Both groups were followed up for 12 to 18 months with an average of(14.5±2.1)months.The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2%,100%,58.3%,88.9%,respectively,which were better than 44.4%,83.3%,33.3%,66.7%in control group(P<0.05).There was no statistical significance in planning of femoral head prosthesis size(P>0.05).The actual combined eccentricity difference and combined eccentricity difference(practical-planning)in Al-HIP group were 1.0(0.2,2.4)mm and 1.1(-2.1,3.2)mm,respectively;which were better than 3.0(1.4,4.9)mm and 3.5(-1.6,6.5)mm in control group(P<0.05).There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter(P>0.05).In AI-HIP group,the actual difference of lower extremity length after surgery,the difference of lower extremity length(practical-planning),osteotomy height from the upper margin of lesser trochanter(practical-planning),actual topshoulder distance after surgery,and topshoulder distance(practical-planning)were 1.5(0.2,2.8),1.1(-0.3,2.2),2.1(-2.3,4.1),(15.3±4.1),2.2(-4.8,0.3)mm,respectively;which were better than control group of 2.6(1.3,4.1),2.5(0.3,3.8),5.8(-2.4,7.7),(13.0±4.3),-5.7(-9.4,-2.2)mm(P<0.05).At final follow-up,there were no significant differences in Harris scores of pain,function,deformity,total scores and VAS between two groups(P>0.05).The range of motion score was 4.8±0.6 in AI-HIP group,which was higher than that in control group(4.4±0.8)(P<0.05).Conclusion Compared with traditional template planning,AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk,restor-ing joint eccentricity,planning lower limb length,osteotomy height and top shoulder distance on the first unilateral THA,and the clinical follow-up effect is satisfactory.

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