1.Hypoglycemic Effect and Mechanism of ICK Pattern Peptides
Lin-Fang CHEN ; Jia-Fan ZHANG ; Ye-Ning GUO ; Hui-Zhong HUANG ; Kang-Hong HU ; Chen-Guang YAO
Progress in Biochemistry and Biophysics 2025;52(1):50-60
Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM1, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.
2.Effects of miR-204-3p inhibitor on epithelial-mesenchymal transition and silicosis fibrosis in silicon dioxide-induced alveolar epithelial cells
Fang CHEN ; Jing YU ; Wenxuan HU ; Yangyang PI ; Xi ZHANG ; Luning WANG ; Ping ZHAO ; Faxuan WANG
Journal of Environmental and Occupational Medicine 2025;42(5):622-629
Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL−1 silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.
3.Safety and puncture accuracy of visual dilated sheath combined with needle nephroscope percutaneous nephroscopy for renal calculi
Huaijun LIU ; Shaoshan WU ; Fang CHEN ; Wenlian HU ; Qilin SUN ; Cheng ZHANG ; Tao TAO
Journal of Modern Urology 2025;30(4):300-305
Objective: To compare the clinical efficacy of visual dilated sheath combined with needle nephroscope percutaneous nephrolithotomy (PCNL) with traditional PCNL for renal calculi,so as to enhance the intraoperative safety and puncture accuracy. Methods: A retrospective analysis was conducted on 100 patients with renal calculi treated on hospital during Sep.2022 to Sep.2023.Based on the surgical approaches,patients were divided into the needle nephroscope group (PCNL with visual dilator sheath and needle nephroscope,n=52) and traditional group (traditional PCNL,n=48).Clinical characteristics,surgical parameters,and outcomes were compared between the two groups. Results: There were no significant differences between the two groups in baseline data,total operation time and hospital stay (P>0.05).The needle nephroscope group had a longer channel establishment time compared to the traditional group [20.0(17.0-22.0) min vs.16.0 (15.0-21.0) min,P=0.002],but significantly shorter puncture time [2.0 (1.0-2.6) min vs. 2.8(2.0-3.5) min,P<0.001],and fewer adjustments of the puncture needle (9.6% vs. 64.6%,P<0.001).The channel was successfully established on the first attempt in all patients in the needle nephroscope group,while only 41 of patients in the traditional group achieved success on the first attempt,6 cases needed 2 attempts,and 1 case needed 3 attempts.Postoperative complications were absent in the needle nephroscope group,whereas postoperative bleeding requiring interventional treatment occurred in 1 case in the traditional group.There was no significant difference in the first-stage stone-clearance rate between the two groups (88.4%vs. 85.4%,P=0.872). Conclusion: PCNL using a visual dilator sheath combined with a needle nephroscope achieves a comparable first-stage stone-clearance rate to traditional PCNL.However,it offers significant advantages in terms of shorter puncture time,fewer adjustments of the puncture needle,and lower postoperative complication rate.These findings suggest superior safety and precision,making it a valuable technique for clinical application.
4.Effect of Dictamni Cortex on Intestinal Barrier Damage by Untargeted Metabolomics and Targeted Metabolomics for Short-chain Fatty Acids
Xiaomin XU ; Donghua YU ; Yu WANG ; Pingping CHEN ; Jiameixue WO ; Suxia JIA ; Wenkai HU ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):40-47
ObjectiveThis study aims to investigate the effect of Dictamni Cortex on intestinal barrier damage in rats and its mechanism by untargeted metabolomics and targeted metabolomics for short-chain fatty acids (SCFAs). MethodsRats were randomly divided into a control group, a high-dose group of Dictamni Cortex (8.1 g·kg-1), a medium-dose group (2.7 g·kg-1), and a low-dose group (0.9 g·kg-1). Except for the control group, the other groups were administered different doses of Dictamni Cortex by gavage for eight consecutive weeks. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the ileal tissue. Enzyme-linked immunosorbent assay (ELISA) was employed to detect the level of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in the ileal tissue of rats. Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) technology was used to detect the expression level of tight junction proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1 mRNAs, in the ileal tissue of rats to preliminarily explore the effects of Dictamni Cortex on intestinal damage. The dose with the most significant toxic phenotype was selected to further reveal the effects of Dictamni Cortex on the metabolic profile of ileal tissue in rats by non-targeted metabolomics combined with targeted metabolomics for SCFAs. ResultsCompared with the control group, all doses of Dictamni Cortex induced varying degrees of pathological damage in the ileum, increased TNF-α (P<0.01), IL-6 (P<0.01), and IL-1β (P<0.01) levels in the ileal tissue, and decreased the expression level of ZO-1 (P<0.05, P<0.01), Occludin (P<0.01), and Claudin-1 (P<0.05) in the ileal tissue, with the high-dose group showing the most significant toxic phenotypes. The damage mechanisms of the high-dose group of Dictamni Cortex on the ileal tissue were further explored by integrating non-targeted metabolomics and targeted metabolomics for SCFAs. The non-targeted metabolomics results showed that 21 differential metabolites were identified in the control group and the high-dose group. Compared with that in the control group, after Dictamni Cortex intervention, the level of 14 metabolites was significantly increased (P<0.05, P<0.01), and the level of seven metabolites was significantly decreased (P<0.05, P<0.01) in the ileal contents. These metabolites collectively acted on 10 related metabolic pathways, including glycerophospholipids and primary bile acid biosynthesis. The quantitative data of targeted metabolomics for SCFAs showed that Dictamni Cortex intervention disrupted the level of propionic acid, butyric acid, acetic acid, caproic acid, isobutyric acid, isovaleric acid, valeric acid, and isocaproic acid in the ileal contents of rats. Compared with those in the control group, the level of isobutyric acid, isovaleric acid, and valeric acid were significantly increased, while the level of propionic acid, butyric acid, and acetic acid were significantly decreased in the ileal contents of rats after Dictamni Cortex intervention (P<0.05, P<0.01). ConclusionDictamni Cortex can induce intestinal damage by regulating glycerophospholipid metabolism, primary bile acid biosynthesis, and metabolic pathways for SCFAs.
5.Correlation between screen time, screen behavior type and anxiety, depression among children and adolescents in Jiangxi Province
CHEN Ting, LUO Yaling, HU Huaxiong, SONG Xiaoguang, CHEN Fuhui, FAN Yi, FANG Xiaoyan, ZHU Hui
Chinese Journal of School Health 2024;45(3):370-374
Objective:
To analyze the status and correlation between screen time, screen behavior type, and anxiety, depression among children and adolescents in Jiangxi Province, so as to provide a basis for effective intervention measures.
Methods:
Using the method of stratified random sampling, 8 851 primary and secondary school students in 11 districts of Jiangxi Province were investigated by questionnaire during September to December in 2020. Anxiety and depression status were investigated using the State Trait Anxiety Inventory (STAI) and the Center for Epidemiological Studies Depression Scale for Children(CES-DC), respectively. Single factor analysis using χ 2-test, t-test,analysis of variance,and multivariate analysis using generalized linear models.
Results:
On school days and weekends, 4.7% and 20.4% of primary and secondary school students in Jiangxi Province had a total screen time of over 2 hours per day, respectively. The weighted scores of the total screen time (primary school students: 1.88± 0.68, junior middle school students: 1.96±0.71, high school students: 2.03±0.80) and time spent for playing video games (primary school students: 1.51±0.64, junior middle school students: 1.62±0.69, high school students: 1.68±0.75) daily showed an upward trend with the increase of educational stage ( F =31.48, 42.13), and with significantly higher in boys (1.97±0.74, 1.66± 0.72) than girls (1.93±0.72, 1.53±0.66)( t =2.48, 9.07)( P <0.05). The average scores of state anxiety and trait anxiety were (42.20±9.05) and (40.65±9.85), which showed an upward trend with the increase of educational stage ( F =168.12, 241.98 ), and were higher in girls than boys ( t =6.63, 8.48)( P <0.01). The average score of depression was (11.99±11.00), which was lower in elementary school students than middle school students and high school students ( F =136.42), with significantly higher in girls ( t =6.85)( P <0.01). On school days, with the increase of total screen time and time spent for playing video games daily, the risk of state anxiety, trait anxiety, and depression among primary and secondary school students significantly increased ( OR = 6.70- 818.98, P <0.01). On weekends, among primary and secondary school students, the total screen time of >1-2 hours daily reduced the risk of state anxiety ( OR =0.30). The risk of developing trait anxiety among students playing video games for more than 2 hours daily was 2.50 times higher than those without screen behavior ( OR =2.50). The risk of developing depression with a total screen time of more than 2 hours daily was 3.15 times higher those whithout screen behavior ( OR =3.15). The risk of developing depression among students playing video games >0-1, >1-2, >2 h daily was 2.14, 2.50, 4.90 times that of those without screen behaviors ( OR =2.14, 2.50, 4.90), and showed an upward trend with the increase of educational stage ( P <0.05).
Conclusions
Screen behaviors of primary and middle school students in Jiangxi Province are positively associated with the risk of anxiety and depression, but the total daily video time of >1-2 h on weekends was negatively associated with state anxiety. It is necessary to control the screen time as much as possible and reduce the risk of anxiety and depression.
6.Intervention effect of miR-204-3P on silica dust-induced silicosis fibrosis in rats
Wenxuan HU ; Jing YU ; Fang CHEN ; Yangyang PI ; Ziming JIAO ; Faxuan WANG
Journal of Environmental and Occupational Medicine 2024;41(4):367-374
Background Long-term exposure to free silica particles will lead to fibrosis of lung tissue, and abnormal expression of microRNA (miRNA) may affect the occurrence and process of fibrosis. Objective To observed possible intervention effect of miR-204-3p overexpression adenovirus on silicosis fibrosis induced by silica dust using a silicosis rat model via non-exposed intratracheal instillation. Methods Forty SD rats were randomly divided into four groups: control group, silicosis model group, miRNA-NC group, and miR-204-3p intervention group. Under ether anesthesia, rats in the silicosis model group, miRNA-NC group, and miR-204-3p intervention group were injected with 1 mL (50 mg·mL−1) of free silica dust suspension into the trachea, while the control group was injected with the same volume of normal saline. After 30 d of dust exposure, the miR-204-3p intervention group was injected with rno-mir-204 adenovirus vector to overexpress miR-204-3p, and the miRNA-NC group was given empty virus vector. After 30 d of normal feeding, the animals were sacrificed by chloral hydrate anesthesia, and the lung tissue was taken for subsequent experiments. The relative expression level of miR-204-3p in lung tissue of rats in each group was detected by real-time fluorescence quantitative PCR (RT-qPCR). HE staining, Masson staining, and Sirius red staining were used for pathological observation. Immunohistochemistry was used to detect the expression of Fibronectin and Collagen I in lung tissue of rats in each group. RT-qPCR was used to detect the relative gene expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Western blot was used to detect the protein expression levels of fibrosis markers Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in each group. Results The anatomical features of lung tissue in the control group were pink lung tissue with soft texture and smooth surface, while those in the silicosis model were grayish white tissue with hard texture and scars and grayish white silicon nodules on the surface. Compared with the silicosis model group, the color of lung tissue in the miR-204-3p intervention group became ruddy, the surface was smooth, and the texture became soft. The staining results showed that the alveolar wall of the control group was thin, there were a small number of capillaries in the alveoli, and the alveolar structure was clear and complete. In the silicosis model group, the alveolar wall became thicker, the pulmonary septum was partially broken, the alveolar structure was defective, and a large amount of collagen fibers were deposited. The alveolar structure of the miR-204-3p intervention group was relatively clear and there was a small amount of collagen fiber deposition. RT-qPCR results showed that compared with the control group, the relative expression levels of miR-204-3p in lung tissue of the silicosis model group and the miRNA-NC group were decreased (P<0.05), and the relative expression level of miR-204-3p in lung tissue of the miR-204-3p intervention group was increased (P<0.05). The results of immunohistochemistry showed that compared with the control group, the expression levels of Fibronectin and Collagen I in lung tissue of the silicosis model group were increased (P<0.05). Compared with the silicosis model group, the relative expression levels of Fibronectin and Collagen I in lung tissue of the rats in the miR-204-3p intervention group were significantly decreased (P<0.05). The results of RT-qPCR and Western blot showed that compared with the control group, the relative protein and gene expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of the silicosis model group increased (P<0.05). Compared with the silicosis model group, the relative gene and protein expression levels of fibrosis factors Fibronectin, Vimentin, Collagen I, and Collagen III in lung tissue of rats in the miR-204-3p intervention group were decreased (P<0.05). Conclusion Silica dust can cause lung fibrosis in rats, and overexpression of miR-204-3P in vivo can reduce silicosis fibrosis in rats caused by silica dust.
7.Network meta-analysis of the modeling effects of different factors on rabbit models of steroid-induced osteonecrosis of femoral head
Zhixing HU ; Qun LI ; Chao YANG ; Xiaoxiao WANG ; Luochangting FANG ; Wuqiong HOU ; Na LIN ; Weiheng CHEN ; Chunfang LIU ; Ya LIN
Chinese Journal of Tissue Engineering Research 2024;28(6):976-984
OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.
8.Effect and mechanism of pachymic acid on renal function and fibrosis in rats with chronic renal failure
Bin PENG ; Xue FENG ; Li FENG ; Wei XIONG ; Xi HU ; Shuangyi ZHU ; Yang XIAO ; Fang CHEN ; Zhi GAO
China Pharmacy 2024;35(12):1489-1494
OBJECTIVE To investigate the effect of pachymic acid (PA) on renal function and fibrosis in chronic renal failure (CRF) rats and its potential mechanism based on the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway. METHODS Using male SD rats as subjects, the CRF model was established by 5/6 nephrectomy; the successfully modeled rats were divided into model group, PA low-dose, medium-dose and high-dose groups (5, 10, 20 mg/kg PA), high-dose PA+ROCK pathway activator lysophosphatidic acid (LPA) group (20 mg/kg PA+1 mg/kg LPA), with 15 rats in each group. Another 15 rats were selected as the sham operation group with only the kidney exposed but not excised. The rats in each drug group were gavaged and/or injected with the corresponding liquid via the caudal vein, once a day, for 12 consecutive weeks. During the experiment, the general condition of rats was observed in each group. After the last administration, the serum renal function indexes (blood urea nitrogen, serum creatinine, uric acid) of rats in each group were detected, the renal histopathological changes were observed; the renal tubule injury score and the area of renal fibrosis were quantified. The levels of oxidative stress indexes [malondialdehyde (MDA), superoxide dismutase (SOD)] and inflammatory factors (tumor necrosis factor-α, interleukin-1β, interleukin-6), the positive expression rates of connective tissue growth factor (CTGF) and collagen Ⅰ were detected as well as the expression levels of pathway-related proteins (RhoA, ROCK1) and fibrosis- related proteins (transforming growth factor-β1, bare corneum homologs 2, α-smooth muscle actin) were determined. RESULTS Compared with the sham operation group, the rats in model group had reduced diet, smaller body size, listless spirit and sluggish response, reduced and atrophied glomeruli, dilated renal tubules with chaotic structure, and a large number of inflammatory cells infiltrated interstitium; the serum levels of renal function indexes, renal tubule injury score, renal fibrosis area proportion, the levels of MDA and inflammatory factors, the positive expression rates of CTGF and collagen Ⅰ, and the expression levels of pathway-related proteins and fibrosis-related proteins in renal tissues were significantly increased, while SOD level was significantly decreased (P<0.05). Compared with the model group, the general condition and pathological injuries of kidney tissue of rats in PA groups were improved to varying degrees,and the above quantitative indexes were significantly improved in a dose-dependent manner (P<0.05). LPA could significantly reverse the improvement effect of PA on the above indicators (P<0.05). CONCLUSIONS PA can improve renal function and alleviate renal fibrosis in CRF rats, which may be related to inhibiting the activation of RhoA/ROCK signaling pathway.
9.Quantitative analysis of early lumbar disc degeneration in young adults by intravoxel incoherent motion in body diffusion-weighted imaging
Fang CHEN ; Mingzhe HU ; Hai WU ; Yaomeng CHEN ; Peipei ZHU
China Modern Doctor 2024;62(12):24-27,36
Objective To explore the predictive value of slow apparent diffusion coefficient(ADCslow),fast apparent diffusion coefficient(ADCfast)and perfusion fraction(f)value of intravoxel incoherent motion in body diffusion-weighted imaging(IVIM-DWI)sequence in early lumbar disc degeneration in young people.Methods The IVIM-DWI technique was used as quantitative magnetic resonance imaging for 120 patients(596 lumbar intervertebral discs)with lower back pain included in Wenzhou People's Hospital.The ADCslow,ADCfast and f values of all lumbar intervertebral discs were measured,and then they were divided into 3 groups according to the Pfirrmann grading standard.SPSS 20.0 statistical software was used to analyze the data.Results The ADCfast value has statistical significance in distinguishing the lumbar intervertebral discs of each group:The area under the curve(AUC)of the normal group vs.the early degenerative group was 0.766,with a sensitivity of 64.2%and a specificity of 78.5%;The AUC of the normal group vs.the mid to late stage degenerative group was 0.822,with a sensitivity of 67.9%and a specificity of 91.3%;The AUC of the early degeneration group vs.the middle and late stage degeneration group was 0.797,with a sensitivity of 62.1%and a specificity of 92.1%.The ADCslow value has statistical significance in distinguishing the lumbar intervertebral discs of each group:AUC=0.707 in the normal group vs.the early degenerative group,with a sensitivity of 83.6%and a specificity of 61.0%;The AUC of the normal group vs.the mid to late stage degenerative group was 0.701,with a sensitivity of 84.5%and a specificity of 58.6%;The AUC of the early degeneration group vs.the middle and late stage degeneration group was 0.668,with a sensitivity of 86.6%and a specificity of 51.0%.The f value cannot distinguish between different groups of lumbar intervertebral discs.Conclusion ADCslow and ADCfast of IVIM-DWI sequence have certain accuracy and specificity in distinguishing the early degeneration of lumbar intervertebral disc in young people,which provides a reliable basis for early clinical treatment.
10.Bioequivalence of amoxicillin clavulanate potassium tablet in healthy volunteers
Yi-Ting HU ; Yu-Fang XU ; Wan-Jun BAI ; Hao-Jing SONG ; Cai-Yun JIA ; Shao-Chun CHEN ; Zhan-Jun DONG
The Chinese Journal of Clinical Pharmacology 2024;40(3):419-424
Objective To evaluate the bioequivalence of test product and reference product in a single dose of amoxicillin clavulanate potassium tablet under fasting and fed conditions in healthy volunteers.Methods An open label,randomized,single dose,four-period,crossover bioequivalence study was designed.Fasting and postprandial tests were randomly divided into 2 administration sequence groups according to 1:1 ratio,amoxicillin clavulanate potassium tablet test product or reference product 375 mg,oral administration separately,liquid chromatography tanden mass spectrometry was applied to determine the concentration of amoxicillin and clavulanate potassium in plasma of healthy subjects after fasting or fed administration,while Phoenix WinNonlin 8.2 software were used for pharmacokinetics(PK)parameters calculation and bioequivalence analysis.Results Healthy subjects took the test product and the reference product under fasting condition,the main PK parameters of amoxicillin are as follows:Cmax were(5 075.57±1 483.37)and(5 119.86±1 466.73)ng·mL-1,AUC0_twere(1.32 × 104±2 163.76)and(1.30 × 104±1 925.11)ng·mL-1,AUC0-∞were(1.32 × 104±2 175.40)and(1.31 ×104±1 935.86)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(3 298.27±1 315.23)and(3 264.06±1 492.82)ng·mL-1,AUC0-twere(7 690.06±3 053.40)and(7 538.39±3 155.89)ng·mL-1,AUC0-∞were(7 834.81±3 082.61)and(7 671.67±3 189.31)ng·mL-1;the 90%confidence intervals of Cmax,AUC0-tand AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00%-125.00%.Healthy subjects took the test and reference product under fed condition,the main PK parameters of amoxicillin are as follows:Cmax were(4 514.08±1 324.18)and(4 602.82±1 366.48)ng·mL-1,AUC0-twere(1.15 × 104±1 637.95)and(1.15 × 104±1 665.69)ng·mL-1,AUC0-∞ were(1.16 × 104±1 646.26)and(1.15 × 104±1 607.20)ng·mL-1;the main PK parameters of clavulanic acid are as follows:Cmax were(2 654.75±1 358.29)and(2 850.51±1 526.31)ng·mL-1,AUC0-twere(5 882.82±2 930.06)and(6 161.28±3 263.20)ng·mL-1,AUC0-∞ were(6 022.70±2 965.05)and(6 298.31±3 287.63)ng·mL-1;the 90%confidence intervals of Cmax,AUC0-t and AUC0-∞ after logarithmic conversion of amoxicillin and clavulanate potassium of the two products were all within 80.00%-125.00%.Conclusion The two formulations were bioequivalent to healthy adult volunteers under fasting and fed conditions.


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