1.Mechanism of tannins from Galla chinensis cream in promoting skin wound healing in rats based on FAK/PI3K/Akt/mTOR signaling pathway.
Wen YI ; Zi-Yi YAN ; Meng-Qiong SHI ; Ying ZHANG ; Jie LIU ; Qian YI ; Hai-Ming TANG ; Yi-Wen LIU
China Journal of Chinese Materia Medica 2025;50(2):480-497
This study investigated the effects and action mechanism of tannins from Galla chinensis cream(TGCC) on the skin wound of rat tail. Male Sprague Dawley(SD) rats were randomly divided into a control group, model group, model+low-dose TGCC(50 mg per rat) group, model+high-dose TGCC group(100 mg per rat), and model+TGC+FAK inhibitor(Y15) cream(100 mg+10 mg per rat) group, with 10 rats in each group. After the rat tail skin injury model was successfully constructed, in the treatment group, corresponding drugs were applied to the wound surface, while in the control and model groups, the same amount of cream base as the TGCC group was applied by the same method. Then, sterile gauze was wrapped around the wound edge, and these operations were performed three times a day for 28 consecutive days. The wound healing status at the third, seventh, eleventh, fourteenth, twenty-first, and twenty-eighth days was recorded, and the wound healing rate and healing time were calculated. On the day after the last dose of medication, rat serum and tail skin wound tissue were collected for analyzing the activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), creatinine(CREA), urea, reactive oxygen species(ROS), interferon gamma(IFN-γ), interleukin(IL)-1β, IL-6, IL-4, IL-10, tumor necrosis factor(TNF)-α, as well as catalase(CAT), glutathione(GSH), lactate dehydrogenase(LDH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC), platelet endothelial cell adhesion molecule-1(CD31), and leukocyte differentiation antigen 34(CD34) in the wound tissue of rat tail skin. Hematoxylin-eosin, Masson, and sirius red staining were used to observe the morphological changes in the wound tissue of rat tail skin. The thickness of the epidermis, the number of fibroblasts and blood vessels, and the contents of collagen fibers, typeⅠ collagen(COLⅠ), and COLⅢ were calculated. The mRNA expressions of keratin 10(KRT10), KRT14, vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), epidermal growth factor(EGF), CD31, CD34, matrix metallopeptidase-2(MMP-2), MMP-9, COLⅠ, COLⅢ, desmin, fibroblast specific protein 1(FSP1), IFN-γ, IL-1β, TNF-α, IL-4, IL-6, and IL-10 in skin wound tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expressions of KRT10, KRT14, VEGF, FGF, EGF, MMP-2, MMP-9, COLⅠ, COLⅢ, desmin, FSP1, focal adhesion kinase(FAK), phosphorylated focal adhesion kinase(p-FAK), phosphatidylin-ositol-3-kinase(PI3K), phosphorylated phosphatidylin-ositol-3-kinase(p-PI3K), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results manifest that TGCC can dramatically elevate the healing rate of rat tail wounds and shorten wound healing time. Besides, it can reduce serum ROS levels, the contents of MDA, MPO, and LDH in the rat skin wound tissue, as well as the serum IFN-γ, IL-1β, IL-6, and TNF-α levels and the mRNA expression levels of IFN-γ, IL-1β, IL-6, and TNF-α in the skin wound tissue. It can elevate the activities of CAT, GSH, SOD, and T-AOC in wound tissue, the IL-4 and IL-10 contents in serum, and the mRNA expressions of IL-4 and IL-10 in the wound tissue. In addition, TGGC can inhibit inflammatory cell infiltration and increase the epidermal thickness, counts of fibroblasts and blood vessels, and contents of collagen fibers, COLⅠ, and COLⅢ. Besides, TGCC can elevate the mRNA and protein expressions of epidermal differentiation markers(KRT10 and KRT14), endothelial cell markers(CD31 and CD34), angiogenesis and fibroblast proliferation, differentiation markers(VEGF, FGF, EGF, COLⅠ, COLⅢ, desmin, and FSP1), reduce the mRNA and protein expressions of gelatinases(MMP-2 and MMP-9), and increase protein expressions of p-FAK, p-PI3K, p-Akt, p-mTOR, as well as ratios of p-FAK/FAK, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. These results suggest that TGCC can significantly facilitate skin wound healing, and its mechanism may be related to the activation of the FAK/PI3K/Akt/mTOR signaling pathway, inhibition of inflammatory cell infiltration in skin wound tissue, elevation of epidermal thickness, counts of fibroblasts and vessels, and contents of collagen fiber, COLⅠ, and COLⅢ, and reduction of MMP-2 and MMP-9 expressions, thus accelerating wound healing.
Animals
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Male
;
Wound Healing/drug effects*
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Rats
;
Rats, Sprague-Dawley
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Signal Transduction/drug effects*
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TOR Serine-Threonine Kinases/genetics*
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Phosphatidylinositol 3-Kinases/genetics*
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Skin/metabolism*
;
Proto-Oncogene Proteins c-akt/genetics*
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Tannins/pharmacology*
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Humans
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Drugs, Chinese Herbal/administration & dosage*
;
Focal Adhesion Kinase 1/genetics*
2.Synthesis, preclinical evaluation and pilot clinical study of a P2Y12 receptor targeting radiotracer 18FQTFT for imaging brain disorders by visualizing anti-inflammatory microglia.
Bolin YAO ; Yanyan KONG ; Jianing LI ; Fulin XU ; Yan DENG ; Yuncan CHEN ; Yixiu CHEN ; Jian CHEN ; Minhua XU ; Xiao ZHU ; Liang CHEN ; Fang XIE ; Xin ZHANG ; Cong WANG ; Cong LI
Acta Pharmaceutica Sinica B 2025;15(2):1056-1069
As the brain's resident immune cells, microglia perform crucial functions such as phagocytosis, neuronal network maintenance, and injury restoration by adopting various phenotypes. Dynamic imaging of these phenotypes is essential for accessing brain diseases and therapeutic responses. Although numerous probes are available for imaging pro-inflammatory microglia, no PET tracers have been developed specifically to visualize anti-inflammatory microglia. In this study, we present an 18F-labeled PET tracer (QTFT) that targets the P2Y12, a receptor highly expressed on anti-inflammatory microglia. [18F]QTFT exhibited high binding affinity to the P2Y12 (14.43 nmol/L) and superior blood-brain barrier permeability compared to other candidates. Micro-PET imaging in IL-4-induced neuroinflammation models showed higher [18F]QTFT uptake in lesions compared to the contralateral normal brain tissues. Importantly, this specific uptake could be blocked by QTFT or a P2Y12 antagonist. Furthermore, [18F]QTFT visualized brain lesions in mouse models of epilepsy, glioma, and aging by targeting the aberrantly expressed P2Y12 in anti-inflammatory microglia. In a pilot clinical study, [18F]QTFT successfully located epileptic foci, showing enhanced radioactive signals in a patient with epilepsy. Collectively, these studies suggest that [18F]QTFT could serve as a valuable diagnostic tool for imaging various brain disorders by targeting P2Y12 overexpressed in anti-inflammatory microglia.
3.Meta-analysis of clinical efficacy of fenestration decompression and curettage in the treatment of jaw cyst
Luliang LIU ; Jinhuan SUN ; Xiaofei WU ; Yuanyuan ZHANG ; Boyu GU ; Fulin GUO
China Modern Doctor 2024;62(31):36-41
Objective Meta-analysis was performed to evaluate the clinical efficacy of fenestration decompression and curettage in the treatment of jaw cyst.Methods Randomized controlled trials comparing fenestration decompression and curettage in treatment of jaw cysts were retrieved from PubMed,Cochrane Library,CNKI,SinoMed,VIP and Wanfang data from built databases to June 2024.A Meta-analysis was performed using RevMan 5.4 software to compare the rate of capsule volume reduction,bone hyperplasia thickness and bone density at 3,6 and 12 months after treatment with two methods.Results A total of 14 literatures were included.At 3,6 and 12 months after operation,rate of capsule volume reduction and bone density after fenestration decompression were significantly better than that after curettage.At 6 and 12 months after operation,bone hyperplasia thickness after fenestration decompression were significantly greater than that after curettage.Conclusion Fenestration decompression is superior to curettage in the treatment of jaw cyst in terms of rate of capsule volume reduction,bone hyperplasia thickness and bone density.
4.Simultaneous determination of 5 kinds of pentacyclic triterpenoids in Chaenomeles speciosa by quantitative analysis of multi-components by single-marker
Tingting ZHANG ; Haoning HU ; Pingyuan LI ; Yongmei HUANG ; Junzhi WANG ; Haiming TANG ; Yonghong YIN
China Pharmacy 2022;33(20):2477-2480
OBJECTIVE To establish a method for simultan eous determination of 5 kinds of pentacyclic triterpenoids as 3-O- acetyl-pomolic acid in Chaenomeles speciosa ,and to analyze the difference in the contents of C. speciosa from different producing areas by different processing technologies . METHODS HPLC method was adopted . The determination was performed on COSMOSIL 5 C18-MS-Ⅱ column with mobile phase consisted of acetonitrile -0.005 mol/L ammonium dihydrogen phosphate solution (pH value adjusted to 6.5 with phosphoric acid )(70∶30,V/V)at the flow rate of 1.0 mL/min. The column temperature was set at 30 ℃. The detection wavelength was set at 210 nm,and sample size was 20 μL. The contents of the other four pentacyclic triterpenoids were calculated according to quantitative analysis of multi -components by single -marker(QAMS)using oleanolic acid as internal reference . The results were compared with those determined by external standard method . The total content of oleanolic acid and ursolic acid ,the total content of 5 components in C. speciosa from different producing areas and different processing technologies were compared . RESULTS The linear range of 3-O-acetyl-pomolic acid ,betulinic acid ,oleanolic acid ,ursolic acid and 3-O-acetyl ursolic acid were 4.06-81.2,2.12-42.4,9.62-192.3,7.77-155.4,4.21-84.1 μg/mL,respectively(R2>0.999). RSDs of precision ,reproducibility and stability (24 h)tests were all lower than 3%. The average recoveries were 98.29%-101.38% (RSDs<3%,n=6). The mass fraction of 3-O-acetyl-pomolic acid ,betulinic acid ,ursolic acid and 3-O-acetyl ursolic acid measured by QAMS w ere 0.023%-0.060%,0.044%-0.528%,0.101%-0.368%,0.067%-0.221%,respectively;the deviations from the results measured by external standard method were all within 8%. The total content of oleanolic acid and ursolic acid, the total content of 5 components in C. speciosa processed by fresh -cut technology from the same producing area were higher than those in C. speciosa processed by traditional technology ,and the total content of 5 components in C. speciosa from Chongqing Qianjiang were significantly higher than those from other producing areas (P<0.05). CONCLUSIONS QAMS method is established for the simultaneous determination of 3-O-acetyl-pomolic acid ,betulinic acid ,oleanolic acid ,ursolic acid and 3-O-acetyl ursolic acid in C. speciosa. Established method is simple ,rapid and accurate . The total content of 5 components in C. speciosa produced in Chongqing Qianjiang is higher ,and the total content of C. speciosa processed by fresh -cut technology from the same origin is higher than C. speciosa processed by traditional technology .
6.Factors Associated with Behaviors Toward End-of-life Care Among Chinese Oncology Nurses: A Cross-Sectional Study
Xiaoyu WU ; Zhihuan ZHOU ; Yiheng ZHANG ; Xiaoyan LIN ; Meng ZHANG ; Fulin PU ; Meifen ZHANG
Asian Nursing Research 2021;15(5):310-316
Purpose:
The goal of this study was to describe the current status of oncology nurses' behaviors toward end of life (EOL) care in China and to explore the factors associated with oncology nurses’ behaviors toward EOL care.
Methods:
A cross-sectional design was applied and a convenience sample of 1038 oncology nurses from 22 grade A hospitals were recruited into this study. A general social demographic data questionnaire was administered, and the Chinese version of Nurses’ Behaviors of Caring for Dying Patients Scale was used to assess nurse behavior toward EOL care. The total score ranges from 40 to 200 points. Data were analyzed with SPSS 26.0 software.
Results:
Chinese oncology nurses' average score of holistic EOL care behaviors was 2.97 ± 0.59. Oncology nurses provide physical care most (3.81 ± 0.76), followed by family care (3.02 ± 0.86), and spiritual care (2.37 ± 0.67). Multiple regression analysis showed that a higher frequency of sharing EOL care experience with colleagues, in-service palliative care education, higher level of head nurse support for EOL patient care, more cases of EOL care, higher working position, and nurse's perceived high level of support were positively associated with behavior toward EOL care. These six factors explained 16.2% of the total variance.
Conclusions
The results may help provide a basis for converting behavior for EOL care among oncology nurses and design interventions to better improve quality of life for EOL patients with cancer in China.
7.Pressurizing and Stretching Experiment in Arterialized Veins of Rabbits
Yuhao ZHANG ; Pei NIU ; Zhimin ZHANG ; Xiaolong NIU ; Wenzeng SHEN ; Liangchao HAO ; Yujuan ZHOU ; Fulin IU
Journal of Medical Biomechanics 2020;35(2):E156-E162
Objective To establish the model of rabbit vena arterialization, so as to investigate the difference of mechanical parameters between arteries and veins as well as before and after arterialization. Methods Twenty-four rabbits were randomly divided into experimental group (n=12) and control group (n=12). By establishing the rabbit vena arterialization model for experimental group, the arterial blood could flow into the veins. After model creation, the vein would be removed 4 weeks after surgery. In the meantime, the external jugular veins and cephalic arteries extracted from control group were acquired. Compressive pressurizing and stretching tests on all vessels were conducted at the same time(including arteries, veins and arterialized veins). Observation was supported by HE staining and immune tissue chemical techniques. Results There were no deaths among the 24 rabbits, with unobstructed blood flow in veins. With the increase of intravascular pressure, the outer diameter of veins changed at first and then stabilized at a fixed value. The elasticity of veins was worse than that of arteries. The external diameter of veins increased rapidly with internal pressure of veins increasing and reached its extreme elasticity. Comparatively, the elasticity of arteries increased slowly. HE staining results showed that thickness of the vascular wall was thinner, while it became thicker after vena arterialization. After vena arterialization, proliferating cell nuclear antigen(PCNA) and α-actin showed positive results. It further proved that proliferation existed among smooth muscle cells, and veins showed the tendency of restenosis again. The elasticity of veins after transplantation into the arterial system was improved compared with that before transplantation. Conclusions Accompanied by the increasing pressure, the vein could reach its elasticity extremity faster than the artery. Under such a long-term high pressure, vein intima was vulnerable. After vena arterialization, with the gradual thickening of vein intima, the tendency of vessel restenosis was obvious, and the elasticity of veins has been improved after transplantation.
8.The clinical efficacy of resection with spleen preservation or containing for benign and borderline tumor in pancreatic tail
Journal of Clinical Surgery 2018;26(2):124-126
Objective To compare the clinical efficacy of the distal pancreatectomy with spleen preservation and the splenectomy in pancreatic tail for the treatment of benign and borderline tumor. Methods A total of 37 patients with pancreatic benign and borderline tumor from January 2012 to De-cember 2014 in our hospital were treated by laparoscopic surgery.Eleven cases were received distal pan-createctomy with spleen preservation(spleen preserving group)and 26 cases were received resection of pancreatic tail with spleen containing(splenectomy group).Results The operation time of spleen preser-ving group and splenectomy group were(165.34 ± 12.25)mins and(170.72 ± 14.37)mins(P>0.05). The blood loss in the preserving spleen group(108.52 ± 13.11)ml was significantly less than that in the splenectomy group(186.25 ± 17.43)ml(P <0.05).The hospitalization time of the preserving spleen group(10.16 ± 2.11)d was significantly shorter than that of the splenectomy group(12.78 ± 2.78)d(P<0.05).The use of Octreotide in the preserving spleen group(11.45 ± 3.75)mg was significantly less than that in the splenectomy group(16.75 ± 5.75)mg(P <0.01).All patients were followed up for three years.The disease free survival(DFS)in the spleen preserving group was higher than that in the splenecto-my group(100% vs.88.46%)with P<0.05.Conclusion The distal pancreatectomy with spleen preser-vation is safe,effective and suitable for pancreatic benign and borderline tumors.
9.Effect of serum interleukin-21 on B cell secretory capacity and apoptosis in patients with systemic lupus erythematosus
Leting ZHENG ; Lidan ZHAO ; Cheng ZHAO ; Yan ZHAO ; Xuan ZHANG ; Fengchun ZHANG ; Xiaofeng ZENG ; Fulin TANG ; Xin YOU
Chinese Journal of Internal Medicine 2017;56(2):116-120
Objective To investigate the secretory capacity and apoptosis of interleukin ( IL)-21 induced normal B cells by co-culture with serum from patients with systemic lupus erythematosus (SLE). Methods Serum from twenty new-onset SLE patients and 20 healthy donors were collected .CD1+9 B cells from the normal controls were co-cultured with serum from SLE patients in the presence or absence of IL-21-R-FC(4 μg/ml).Supernatant IgG and IgM concentration were measured by immunoturbidimetric assay on day 5.Supernatant anti-dsDNA level was determined by ELISA .The percentage of apoptotic cells was detected by flow cytometer.Results IgG,IgM and anti-dsDNA levels in normal B cells with SLE serum were significantly higher than those in the serum of SLE patients alone [ ( 5.84 ±1.79 ) g/L vs ( 4.25 ± 1.48)g/L,P=0.000;(0.46 ±0.21)g/L vs (0.43 ±0.21)g/L,P=0.003;(127.76 ±70.24)IU/ml vs (115.15 ±63.88) IU/ml,P=0.014 respectively].However, no significant differences were found in the group of normal B cells with non-homologous serum from normal controls (P>0.05).Supernatant IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum significantly decreased while IL-21R-fusion protein was added [(5.26 ±1.62)g/L vs (5.84 ±1.79)g/L, P=0.006;(0.42 ±0.20)g/L vs (0.46 ±0.21)g/L, P=0.002;( 118.00 ±69.62 ) IU/ml vs ( 127.76 ±70.24 ) IU/ml, P =0.012 respectively ] .The apoptotic rate of B cells with SLE serum was significantly higher than that with normal serum [ ( 47.88 ± 12.65)%vs (38.86 ±10.32)%,P =0.004].But adding IL-21R-fusion conversed the apoptotic rates [(42.08 ±12.52)%vs (47.88 ±12.65)%,P=0.001].Conclusions SLE serum could induce normal B cells to form immunoglobulin secreting cells and producing autoantibodies , or apoptosis in pathological conditions.IL-21 might be considered as a potential therapeutic target of SLE .
10.Effects of constant light exposure on obesity in high fat diet rats
Fangzhi YUE ; Ke XIA ; Fulin LIU ; Yingying ZHENG ; Qian HOU ; Cai PENG ; Dongmei ZHANG
Chinese Journal of Endocrinology and Metabolism 2017;33(12):1057-1062
Objective To observe the effects of constant light exposure on the obesity in high fat diet rats. Methods Thirty-two male SD rats were randomly divided into four groups:rats on a normal chow exposed to standard light-dark cycle ( group A) , rats on a normal chow exposed to constant light ( group B) , rats on a high fat diet exposed to standard light-dark cycle ( group C) , and rats on a high fat diet exposed to constant light ( group D) . Body weights and food intakes were recorded weekly throughout the 12-week study. Body weight, fat mass, visceral adipose tissue weight, intraperitoneal glucose tolerance test ( IPGTT) results, insulin resistance parameters, serum lipids and levels of interleukin 6 (IL-6), tumor necrosis factor-α(TNF-α) were compared among groups. Epididymal adipose tissues mRNA expression of circadian clock genes, i. e. clock, bmal1, rorα, rev-erbα, cry1, per1, and per2 were analyzed by realtime PCR. Results From the 9th week, body weights of rats in group D were significantly higher than those in group C (all P<0. 05). At the 12th week, area under curve of IPGTT (AUC-IPGTT) in groups B, C, and D were significantly higher than that in group A. AUC-IPGTT in group D was significantly higher than that in group C (all P<0.05). Compared with group C,asignificant increase in fat mass,visceral adipose tissue weight,homeostasis model assessment for insulin resistance, serum cholesterol, TNF-α levels were observed in group D ( all P<0. 05). And a significant decrease in quantitative insulin sensitivity check index ( QUICKI) and high density lipoprotein-cholesterol were observed in group D in comparison with group C (both P<0. 05). Circadian clock genes (clock, rorα, rev-erbα, cry1, per1) mRNA expressions in group B and D were significantly different from those in group A (all P<0. 05) . Expression of cry1 in group D was significantly higher than that in group C. In group C, rev-erbαmRNA expression was significantly down-regulated in comparison with group A (P<0. 05). Conclusion Constant light exposure exaggerates obesity, glycolipid metabolism abnormality, inflammation, and insulin resistance in high fat diet rats.

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