1.Research progress on the mechanism of action of rosmarinic acid in the prevention of cardiovascular diseases
Ke CAI ; Sheng-ru HUANG ; Fang-fang GAO ; Xiu-juan PENG ; Sheng GUO ; Feng LIU ; Jin-ao DUAN ; Shu-lan SU
Acta Pharmaceutica Sinica 2025;60(1):12-21
With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.
2.Bugansan Regulates R-spondin1/Wnt3a-mediated Intestinal Injury to Ameliorate Digestion and Absorption Dysfunction in Rat Model of Aging Induced by D-galactose
Yixuan WANG ; Ran HUO ; Jin TIAN ; Fang FANG ; Na LIU ; Jiepeng WANG ; Chaoyi FANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):19-27
ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway, and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups: blank control, model, low-, medium-, and high-dose (7.03, 14.06, 28.12 g·kg-1, respectively) Bugansan, and vitamin E (suspension, 27 mg·kg-1), with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose (400 mg·kg-1), while the blank control group was injected with normal saline. Since the day of modeling, rats in intervention groups received corresponding agents by gavage, and those in blank control and model groups received an equal volume of normal saline (10 mL·kg-1). General biological features such as fur color, activity, body mass, water intake, and food intake were observed. Meanwhile, the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the serum were measured to assess aging. Grip strength and the content of total bile acids (TBA) and the activity of α-amylase (AMY) in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase (β-gal) in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 (GLP-1), vasoactive intestinal peptide (VIP), and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi1) and leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) in the duodenal tissue. Moreover, Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to quantify the mRNA levels of Ki67, Bmi1, and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally, the mRNA levels of R-spondin1, Wnt3a, β-catenin, and glycogen synthase kinase-3β (GSK-3β) and the protein levels of R-spondin1, Wnt3a, β-catenin, and phosphorylated GSK-3β (p-GSK-3β) in the duodenum were determined by Real-time PCR and Western blot, respectively, to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group, the model group showed decreases in body mass, water intake, food intake, grip strength, activities of SOD, GSH-Px, and AMY in the serum and content of GLP-1, VIP and D-xylose in the serum (P<0.05), increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum (P<0.05), reductions in villus length, villus width, crypt depth, and villi/crypt (V/C) value, down-regulated mRNA and protein levels of Ki67, Lgr5, Bmi1, R-spondin1, Wnt3a, β-catenin, and up-regulated level of GSK-3β, phosphorylation (p)-GSK-3β (P<0.05). Compared with the model group, Bugansan increased the body mass, water intake, food intake, grip strength, and activities of SOD, GSH-Px, and AMY and levels of GLP-1, VIP and D-xylose in the serum (P<0.05), while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum (P<0.05). Furthermore, Bugansan increased the villus length, villus width, crypt depth, and V/C value, up-regulated the mRNA and protein levels of Ki67, Lgr5, Bmi1, R-spondin1, Wnt3a, β-catenin, and down-regulated the level of GSK-3β and p-GSK-3β (P<0.05). ConclusionAging rats exhibit obvious impairments in digestion and absorption functions, accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions, ultimately contributing to the delay of aging.
3.Improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis
Pengfei XIA ; Di JIN ; Jin LIANG ; Yi YU ; Jinjun DU ; Zhanyong JIN ; Jun FANG ; Xia YANG ; Huiwu LIU
China Pharmacy 2025;36(11):1311-1316
OBJECTIVE To investigate the improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis (CAG). METHODS Rats were randomly assigned into normal control group, model group, Xiangsha yiwei tang low-, medium- and high-dose groups (6, 12, 18 g/kg, calculated by crude drug), and high-dose group of Xiangsha yiwei tang+740 Y-P [Xiangsha yiwei tang 18 g/kg+transforming growth factor β1/phosphatidyl inositol 3 kinase/ protein kinase B(TGF-β1/PI3K/Akt) pathway activator group 740 Y-P 10 mg/kg], with 18 rats in each group. Rats in each group were administered the corresponding drugs via oral gavage or injection, once daily, for 4 consecutive weeks. Gastric mucosal blood flow, the levels of serum gastrointestinal hormones [including motilin (MTL), gastrin (GAS), and pepsinogen (PP)], as well as inflammatory cytokines [including tumor necrosis factor- α (TNF- α), interleukin-1β (IL-1β), IL-6] in rats were measured. Pathological damage to gastric mucosal tissue was observed in rats; the apoptotic rate of gastric mucosal cells was detected. The expressions of TGF-β1/PI3K/Akt signaling pathway-related proteins and apoptosis-related proteins [including B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax)] in the gastric mucosal tissues of rats were assessed. RESULTS Compared with normal control group, model group had abnormal gastric mucosal tissue structure, with shedding of gastric mucosal epithelial cells, and prominent infiltration of inflammatory cells. Gastric mucosal blood flow, the serum levels of MTL, GAS, PP, and Bcl-2 protein expression were lowered significantly, while serum levels of TNF-α, IL-1β and IL-6, apoptosis rate, protein expressions of Bax and TGF-β1, the phosphorylations of PI3K and Akt were increased significantly (P<0.05). Compared with model group, Xiangsha yiwei decoction groups exhibited attenuated histopathological injuries in gastric mucosal tissues, reduced inflammatory cell infiltration, and significant improvements in the aforementioned quantitative parameters (P<0.05). Compared with high-dose group of Xiangsha yiwei tang, high-dose group of Xiangsha yiwei decoction combined with 740 Y-P exhibited significantly aggravated histopathological injuries in gastric mucosal tissues, and the aforementioned quantitative parameters were markedly reversed (P<0.05). CONCLUSIONS Xiangsha yiwei tang can alleviate gastric mucosal damage in CAG rats, and its mechanism of action is related to the inhibition of TGF-β1/PI3K/Akt signaling pathway.
4.Preliminary application of foldable pedicled latissimus dorsi myocutaneous flap for repairing soft tissue defects in shoulder and back.
Jian ZHOU ; Yucen ZHENG ; Shune XIAO ; Zairong WEI ; Kaiyu NIE ; Zhiyuan LIU ; Shusen CHANG ; Wenhu JIN ; Wei CHEN ; Fang ZHANG
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(1):69-73
OBJECTIVE:
To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back.
METHODS:
Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage.
RESULTS:
All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site.
CONCLUSION
The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.
Male
;
Female
;
Humans
;
Young Adult
;
Adult
;
Middle Aged
;
Plastic Surgery Procedures
;
Myocutaneous Flap/surgery*
;
Shoulder/surgery*
;
Skin Transplantation
;
Superficial Back Muscles/transplantation*
;
Soft Tissue Injuries/surgery*
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Wound Healing
;
Treatment Outcome
;
Perforator Flap
5.Budget impact analysis for adjusting the price of carotid endarterectomy over the next five years
Zhe-Yi FANG ; Jin-Yu LIU ; Jia-Yan HUANG
Fudan University Journal of Medical Sciences 2024;51(2):230-237
Objective To analyze the budget impact of a price increase for carotid endarterectomy(CEA)on the total expenditure of health insurance expenditure in China.Methods We set 2021 as the base year,and 2022-2026 as the study years.A budget impact analysis model was developed to calculate the expenditure of health insurance funds over the next 5 years following a 30%price increase for carotid endarterectomy.Data on the target population,treatment costs,and market share changes both nationwide and in four sample cities were used.The data was collected in May to Jul 2022.Results The price increase for carotid endarterectomy will reduce total health insurance fund expenditures nationwide by 143.176 2 million yuan over five years.Total health insurance fund expenditures in the sample cities will also decrease to varying degrees.The higher the price increase for the surgical procedure,the greater the decrease in total expenditure of the health insurance fund.The market share of the surgical procedure has the greatest impact on the total expenditure of the health insurance fund.Conclusion Increasing the price of carotid endarterectomy may lead to increase in its market share and decline in the health insurance fund expenditures in future five years.
6.Finite element model establishment and stress analysis of lumbar-sacral intervertebral disc in ankylosing spondylitis
Zhijie KANG ; Zhenhua CAO ; Yangyang XU ; Yunfeng ZHANG ; Feng JIN ; Baoke SU ; Lidong WANG ; Ling TONG ; Qinghua LIU ; Yuan FANG ; Lirong SHA ; Liang LIANG ; Mengmeng LI ; Yifei DU ; Lin LIN ; Haiyan WANG ; Xiaohe LI ; Zhijun LI
Chinese Journal of Tissue Engineering Research 2024;28(6):840-846
BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.
7.Biomechanical features of posterior"Y"osteotomy and fixation in treatment of ankylosing spondylitis based on finite element simulation analysis
Le ZHANG ; Zhenhua CAO ; Yunfeng ZHANG ; Yangyang XU ; Feng JIN ; Baoke SU ; Lidong WANG ; Xing WANG ; Ling TONG ; Qinghua LIU ; Yuan FANG ; Lirong SHA ; Haiyan WANG ; Xiaohe LI ; Zhijun LI
Chinese Journal of Tissue Engineering Research 2024;28(12):1842-1848
BACKGROUND:Ankylosing spondylitis is a progressive inflammation of spinal stiffness deformity caused by tissue ossification and fibrosis.The posture of ankylosing spondylitis patients is abnormal and their activities are limited that minor injuries can lead to thoracolumbar fractures.Traditional medical image observation limits doctors'preoperative decision planning and postoperative disease prevention for ankylosing spondylitis treatment. OBJECTIVE:Based on the spinal model of ankylosing spondylitis patients before and after posterior spinal cancellous ossification osteotomy("Y"osteotomy for short),to explore the biomechanical changes of"Y"osteotomy and fixation in the treatment of ankylosing spondylitis. METHODS:Based on the preoperative and postoperative CT images of an ankylosing spondylitis patient who went to the Second Affiliated Hospital of Inner Mongolia Medical University,a three-dimensional spine model(T11-S1)before and after"Y"osteotomy(L3 osteotomy)was reconstructed in Mimics 19.0 software.A 7.5 Nm torque was applied to the top of T11 vertebral body to simulate the movement of the spine under six conditions:flexion,extension,left bending,right bending,left rotation and right rotation.Finally,the range of motion of each vertebral body,the stress of each intervertebral disc,and the stress of the screw rod system were simulated. RESULTS AND CONCLUSION:(1)After"Y"type osteotomy and posterior fixation,the range of motion of all vertebrae in the spine decreased,and the loss rate of upper vertebrae was large(L1:77.95%).(2)The maximum stress of the spinal intervertebral disc before operation occurred at the L1-L2 segment(0.55 MPa),and the maximum stress of the spinal intervertebral disc after operation occurred at the T11-T12 segment(0.50 MPa),and the stress of intervertebral disc below T12 was far less than that before operation.(3)The maximum stress of the screw rod system(166.67 MPa)occurred in the upper and middle segments of the rod body and the root of the pedicle screw.(4)In conclusion,the"Y"type posterior fixation operation enhances the stability of the spine and reduces the range of motion of the spine.The vertebral body decompression of the fixed segment is great and the stress-shielding phenomenon of the lower vertebral body is significant.The stiffness of the rod body and the stress concentration area of the pedicle screw should be strengthened to avoid the fracture of the rod caused by stress fatigue.
8.Best evidences for postpartum follow-up in patients with gestational diabetes
Liu YANG ; Jing QIAN ; Lijuan YANG ; Fang XUE ; Mengfan JIANG ; Jin GAO ; Jinzhi LI
Modern Clinical Nursing 2024;23(2):65-71
Objective To summarise the best evidence for postpartum follow-up acquired from patients with gestational diabetes mellitus so as to provide an evidence-based reference for establishment of a postpartum follow-up program.Methods Literature on postpartum blood glucose follow-up in patients with gestational diabetes mellitus was retrieved from 17 major databases including BMJ Best Practice,UpToDate,Joanna Briggs Institute(JBI),International Guide Collaboration Network,National Institute for Health and Care Excellence(NICE),American Diabetes Association website,Medlive,Cochrane Library,Embase,OVID,PubMed,Web of Science,Quanfang local PubMed,CNKI,Wanfang Data,VIP,and Sinomed from the inception of databases to July 2023.The literature to be retrieved included guidelines,expert consensus,evidence summaries,systematic reviews,clinical decisions,and the original studies.Results A total of 9 articles,five practice guidelines,a systematic review,an evidence summaries,an expert consensus and a clinical decisions,were included.Totally,17 pieces of best evidence were summarised from the five aspects:postpartum blood glucose,lifestyle guidance,breastfeeding,drug treatment and health education.Conclusions The summarised best evidences can provide evidence-based references for postpartum follow-up of patients with gestational diabetes.Nursing staff in hospitals and community health centres should formulate relevant follow-up plans according to the actual postpartum conditions of patients in order to prevent the incidence of postpartum Type Ⅱ diabetes.
9.The effect of levocarnitine on fibrotic proliferation, apoptosis and migration of myocardial cells
Zhaojie LIU ; Li JIN ; Yiwen GU ; Jue SHI ; Haiya WANG ; Ningyuan FANG ; Jin SHU
Chinese Journal of Geriatrics 2024;43(2):203-208
Objective:To investigate the mechanisms underlying the effect of levocarnitine on myocardial cell fibrosis, proliferation, apoptosis and migration.Methods:Between June and December 2022, an overexpression vector for tissue inhibitor-1 of metalloproteinase(TIMP-1)and siRNA TIMP-1 were used to transfect rat H9c2 cardiomyocytes(from the cell bank of the Chinese Academy of Sciences), and transfection efficiency was measured using fluorescence reverse transcription quantitative PCR(RT-qPCR). After treating H9c2 cells with angiotensin Ⅱ(AngⅡ), the expression of the MMP3 and TIMP-1 genes in the cells was detected by RT-qPCR.A CCK8 kit was used to assess the effect of levocarnitine intervention on the proliferation of myofibroblasts after overexpression or knockdown of TIMP-1.The effects of levocarnitine on apoptosis and migration of myofibroblasts were detected by flow cytometry and Transwell assays.Results:The RT-qPCR results showed that the expression level of the MMP3 gene(1.38±0.05)in cardiomyocytes treated with AngⅡ for 24 hours exhibited an upward trend( P<0.01), while the expression level of the TIMP-1 gene(0.71±0.03)showed a downward trend( P<0.01). In addition, H9c2 cells with TIMP-1 overexpression(905.98±24.17)and knockdown(0.18±0.01)%, respectively, were successfully constructed.Based on CCK-8 detection results, knockdown of TIMP-1(86.56±7.98)% was able to promote the proliferation of H9c2 cells induced by levocarnitine( P<0.01). Apoptosis experiments showed that inhibition of TIMP-1 expression(23.22±2.69)significantly reduced the apoptosis level of H9c2 cells induced by levocarnitine( P<0.01). Migration experiments showed that inhibition of TIMP-1 expression(217.67±23.44)significantly promoted the migration ability of H9c2 cells induced by levocarnitine( P<0.01). Conclusions:After intervention to reduce TIMP-1 expression, levocarnitine can promote proliferation, inhibit apoptosis and promote migration of myofibroblasts and may therefore ameliorate myocardial fibrosis.
10.Extraction process,enzymatic properties and practical application of glucuronic hydrolase in Scutellaria baicalensis stems and leaves
Yu-Jie CHENG ; Xu CHEN ; Yun-Hua LIU ; Zhi-Fang HUANG ; Yan CHEN ; Yu-Hong LIU ; Jin-Hai YI
Chinese Traditional Patent Medicine 2024;46(1):35-40
AIM To study the extraction process,enzymatic properties and practical application of glucuronic hydrolase in Scutellaria baicalensis stems and leaves(sbsl GUS).METHODS With granularity,water consumption,extraction time and extraction frequency as influencing factors,enzymatic activity as an evaluation index,the extraction process was optimized by orthogonal test on the basis of single factor test.The relationship between substrate(baicalin)concentration and enzymolysis rate,after which Vmax and Km were calculated,the effects of pH value,temperature and metal ion on enzymatic activity were investigated,pH stability and heat stability were evaluated.sbsl GUS was adotped in the enzymolysis of baicalin to prepare baicalein,then the effects of pH value,temperature,reaction time,initial substrate concentration and enzyme addition on transfer rate were investigated.RESULTS The optimal extraction process was determined to be 40 mesh for granularity,10 times for water consumption,15 min for extraction time,and 3 times for extraction frequency.The enzymolysis accorded with the kinetics of enzymatic reaction,Km was 0.006 3 mol/L,Vmax was 70.42 μmol/h,the strongest enzymatic activity was found at the pH value of 6.0,temperature of 45℃and metal ion of 100 mmol/L Cu2+,sbsl GUS demonstrated good stability at the ranges of 4.0-7.0 for pH value and 4-30℃for temperature.The optimal preparation process was determined to be 6.0 for pH value,45℃for temperature,more than 12 h for reaction time,67.2 mmol/L for initial substrate concentration,and 1 mL/0.269 mmol baicalin for enzyme addition,the transfer rate was 97.83%.CONCLUSION sbsl GUS enzymolysis exhibits high efficiency and mild condition,which can provide a simple preparation method for obtaining baicalein,and expand the application path of Scutellaria baicalensis stems and leaves.

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