1.Internal tension relieving technique assisted anterior cruciate ligament reconstruction to promote ligamentization of Achilles tendon grafts in small ear pigs in southern Yunnan province
Bohan XIONG ; Guoliang WANG ; Yang YU ; Wenqiang XUE ; Hong YU ; Jinrui LIU ; Zhaohui RUAN ; Yajuan LI ; Haolong LIU ; Kaiyan DONG ; Dan LONG ; Zhao CHEN
Chinese Journal of Tissue Engineering Research 2025;29(4):713-720
BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).
2.Characteristics analysis of pediatric medicines with priority review and approval for marketing in China
Haoyu YANG ; Kan TIAN ; Xue YOU ; Hongwei DAN ; Qian WANG ; Xiaoyong YU
China Pharmacy 2025;36(5):519-523
OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China, providing a reference for promoting enterprise R&D and production, as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval, Pharnexcloud biomedical database, and National Medical Insurance Drug Directory, this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30, 2024, a total of 68 pediatric medicines had been approved through the priority review and approval process, covering 12 therapeutic areas, with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days, with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years, with an average of 1.42 years. This included 12 domestic new medicines, 21 domestic generic medicines, 35 imported medicines, as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally, 31 of these medicines had been included in the medical insurance catalog, representing a proportion of 45.59%. CONCLUSIONS Currently, a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding, and the dosage forms are becoming more tailored to children’s needs. However, there are still issues such as slow progress in new medicine development, insufficient stability in the medicine review and approval process, and a need to increase the proportion of medicines included in medical insurance.
3.Mechanism of Kaixuan Jiedu Core Prescription in Regulating PTGS2 to Improve Skin Lesions in Psoriasis Mouse Models
Xue XIAO ; Liping KANG ; Dan DAI ; Yidi MA ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):49-59
ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription (KXJD) and investigate its effective components and therapeutic targets in the treatment of common psoriasis
4.Mechanism of Kaixuan Jiedu Core Prescription in Regulating PTGS2 to Improve Skin Lesions in Psoriasis Mouse Models
Xue XIAO ; Liping KANG ; Dan DAI ; Yidi MA ; Bin YANG ; Ping SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):49-59
ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription (KXJD) and investigate its effective components and therapeutic targets in the treatment of common psoriasis
5.Herbal Textual Research on Asteris Radix et Rhizoma in Famous Classical Formulas
Hengyang LI ; Wenjie LI ; Xiaoying DING ; Dan ZHANG ; Zijing XUE ; Qi AN ; Zhilai ZHAN ; Yuguang ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):20-30
By reviewing the ancient and modern literature, the name, origin, scientific name evolution, place of origin, quality, harvesting, processing, efficacy and toxicity of Asteris Radix et Rhizoma(ARR) were systematically sorted out, so as to provide reference for the development and utilization of the relevant famous classical formulas. According to textual research, ARR was first contained in Shennong Bencaojing, all generations are Ziwan for its proper name, and there are still aliases such as Ziyuan, Ziqian and Xiaobianer. Its mainstream origin in successive generations was Aster tataricus, and there are also Ligularia fischeri and others in local area of use. The medicinal parts of ARR are root and rhizome, but in modern times, the rhizome is mostly used for propagation and cultivation, so some of ARR medicinal materials only have the root without the rhizome. The earliest recorded ancient origin of ARR was now Fangxian(Hubei), Zhengding and Handan(Heibei), then the range of production areas gradually expanded, the mainstream production areas from the Song dynasty to the Ming and Qing dynasties included Hebei, Jiangsu, Anhui, Henan and other places, since modern times, two major producing areas have been formed in Anguo, Hebei province and Bozhou, Anhui province. From the quality evaluation, it is clear that from ancient times, flexible roots and purple color are the best. The ancient harvesting was mainly in lunar February or March, and then dried in the shade, and the modern harvesting is mostly in spring and autumn, and the roots are braided into pigtails and then dried in the sun or dried in the sun after 1-2 d. The ancient and modern processing method of ARR are basically the same, mainly honey processing, there are still methods of frying, steaming, vinegar sizzling, etc. Based on the results, it is recommended that the dried roots and rhizomes of A. tataricus should be used in clinical and the development of related famous classical formulas, and those whose original formulas specify the processing requirements can be processed according to the relevant requirements, while whose processing requirements are not specified should be used in the form of raw products.
6. Mechanism of ellagic acid improving cognitive dysfunction in APP/PS double transgenic mice based on PI3K/AKT/GSK-3β signaling pathway
Li-Li ZHONG ; Xin LU ; Ying YU ; Qin-Yan ZHAO ; Jing ZHANG ; Tong-Hui LIU ; Xue-Yan NI ; Li-Li ZHONG ; Yan-Ling CHE ; Dan WU ; Hong LIU
Chinese Pharmacological Bulletin 2024;40(1):90-98
Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg
7. Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology
Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU ; Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU ; Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU
Chinese Pharmacological Bulletin 2024;40(3):565-573
Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.
8.Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway
Jiaxin GAO ; Jianbo WANG ; Yanan XUE ; Jie SUN ; Dan WANG ; Kun HAN ; Yunyu ZHANG ; Yiran YIN ; Xiaofan FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):10-17
ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan(QWBZS) on diabetic encephalopathy(DE) rat model, and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase-3β(GSK-3β) signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group(8 rats) and high-fat diet group(40 rats). After 12 weeks of feeding, rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin(STZ) for 2 consecutive days to construct a DE model, and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling, according to blood glucose and body weight, model rats were randomly divided into model group, low, medium and high dose groups of QWBZS(3.15, 6.3, 12.6 g·kg-1), combined western medicine group(metformin+rosiglitazone, 0.21 g·kg-1), with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage, and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage, 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin (FINS) level was detected by enzyme-linked immunosorbent assay(ELISA) and insulin resistance index(HOMA-IR) was calculated. Hematoxylin-eosin(HE) staining was used to observe the morphological changes of hippocampus in rats, ELISA was used to detect the indexes of oxidative stress in hippocampal tissues, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to detect mRNA expression levels of PI3K, Akt, nuclear transcription factor-κB(NF-κB), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in hippocampus, and Western blot was used to detect the protein expression of PI3K, Akt, phosphorylated(p)-Akt, GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group, FINS and HOMA-IR values of the model group were significantly increased(P<0.01), the path of finding the original position of the platform was significantly increased, and the escape latency was significantly prolonged(P<0.01), the morphology of neuronal cells in hippocampal tissues was disrupted, the levels of reactive oxygen species(ROS) and malondialdehyde(MDA) in hippocampus of rats were increased, and the activity of superoxide dismutase(SOD) was decreased(P<0.05, P<0.01), mRNA expression levels of PI3K and Akt were decreased(P<0.01), mRNA expression levels of NF-κB, TNF-α and IL-1β were increased(P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly decreased, and the protein expression of GSK-3β was significantly increased(P<0.01). Compared with the model group, the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased(P<0.01), the path of finding the original position of the platform and the escape latency were significantly shortened(P<0.01), the hippocampal tissue structure of rats was gradually recovered, and the morphological damage of nerve cells was significantly improved, the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased(P<0.01), the mRNA expression levels of PI3K and Akt were increased(P<0.01), and the mRNA expression levels of NF-κB, TNF-α and IL-1β were decreased (P<0.05, P<0.01), the protein expression levels of PI3K, p-Akt and p-GSK-3β were significantly increased(P<0.01), and the expression of GSK-3β was significantly decreased(P<0.01). ConclusionQWBZS can alleviate insulin resistance in DE rats, it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.
9.Effects of alfentanil on myocardial fibrosis in rats with acute myocardial infarction by regulating the SphK1/S1P signaling pathway
Jinliang XIAO ; Xue ZOU ; Jiapeng DAN
China Pharmacy 2024;35(8):955-960
OBJECTIVE To explore the effects of alfentanil (ALF) on myocardial fibrosis in rats with acute myocardial infarction (AMI) by regulating sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P) signaling pathway. METHODS Male SD rats were collected to construct AMI model by the ligation of anterior descending branch of left coronary artery. The successfully modeled rats were randomly divided into AMI model group (Model group), ALF low-dose group (ALF-L group, 0.25 mg/kg ALF), ALF high-dose group (ALF-H group, 0.5 mg/kg ALF), high dose of ALF+SphK1 activator group (ALF-H+K6PC-5 group, 0.5 mg/kg ALF+1 μg/g K6PC-5). At the same time, a sham operation group (Sham group) was set up to perform only chest opening/closing operations without ligating the anterior descending branch of left coronary artery, with 15 rats in each group. Rats in each drug group were intraperitoneally injected with the corresponding drug solution, once a day, for 4 consecutive weeks. Twelve hours after the last medication, cardiac function indicators [left ventricular systolic pressure (LVSP), left ventricular ejection fraction (LVEF), left ventricular systolic diameter (LVSD), left ventricular fractional shortening (LVFS)] of rats were detected in each group; the condition of myocardial infarction, pathological changes in myocardial tissue, and degree of fibrosis were observed; serum levels of brain natriuretic peptide (BNP) and cardiac troponin Ⅰ (cTnⅠ) in rats were detected. The protein expressions of collagen Ⅰ , collagen Ⅲ , matrix metalloproteinase-2 (MMP-2), SphK1 and S1P were alsodetected in the myocardial tissue of rats. RESULTS Compared with the Sham group, the arrangement of myocardial cells in the Model group was disordered, with a large number of inflammatory cells infiltrating. The levels of LVSP, LVFS and LVEF in the Model group were significantly reduced (P<0.05); LVSD level, myocardial infarction area, collagen volume fraction, serum levels of BNP and cTnⅠ, the protein expressions of collagen Ⅰ, collagen Ⅲ, MMP-2, SphK1 and S1P in myocardial tissue were significantly increased or enlarged (P<0.05). Compared with the Model group, the pathological changes and degree of fibrosis in the myocardial tissue of rats in each dose group of ALF were improved or relieved, while the quantitative indicators of rats in the ALF-H group were significantly improved and significantly better than those in ALF-L group (P<0.05). K6PC-5 could significantly reverse the improvement effect of high-dose ALF on the above quantitative indicators in rats (P<0.05). CONCLUSIONS ALF can reduce myocardial fibrosis and improve cardiac function in AMI rats, and the effect may be related to the inhibition of the SphK1/S1P signaling pathway.
10.Study on the Mechanism of Guanyuan Mingmen Sequential Acupuncture Activating FSHR/cAMP/PKA Pathway to Promote Granulosa Cell Proliferation in POI Model Rats
Jiang-Hong XU ; Yue-Lai CHEN ; Ping YIN ; Xue-Dan ZHAO ; Hui-Min ZHENG ; Jun-Wei HU ; Lu-Min LIU
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):965-972
Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P<0.01),and the E2 level was significantly decreased(P<0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P>0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P<0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P<0.05),had no difference with the blank group(P>0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P<0.01),still being lower than the blank group(P<0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P>0.05),while the protein expression level of P450arom was lower than that in the model group(P<0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P<0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P<0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P<0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P<0.05 or P<0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.

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