1.Yinqiao Powder affects macrophage polarization-mediated herpes simplex keratitis through the cGAS-STING-IRF3 molecular pathway
Ning YAO ; Rongli ZHAO ; Xuemei YANG ; Yuhuan LIU ; Yaqin DING ; Yan DAI
International Eye Science 2025;25(8):1227-1233
AIM: To investigate the specific molecular mechanism of Yinqiao Powder in affecting macrophage polarization in herpes simplex keratitis(HSK)through the cyclic GMP-AMP synthetase(cGAS)-stimulator of interferon genes(STING)-interferon regulatory factor 3(IRF3)molecular pathway.METHODS:Human corneal epithelial cells(HCE-T)were divided into control, HSK, and HSK + Yinqiao Powder groups. M0 macrophages were grouped as Ctrl, HSV-1, HSV-1+oe-cGAS, HSV-1+Yinqiao Powder, and HSV-1+oe-cGAS+Yinqiao Powder. Conditional medium(CM)from each group of M0 macrophages was collected to intervene in HCE-T cells and divided into Ctrl-CM, HSV-1-CM, HSV-1+oe-cGAS-CM, and HSV-1+Yinqiao Powder-CM groups. Cell viability was detected by MTT assay, and apoptosis was detected by TUNEL assay. ELISA was used to detect the concentrations of Arg-1 and iNOS in cell supernatants, and Western blotting was used to detect the relative protein expressions of cGAS, STING, and IRF3. Balb/c mice were divided into control, model, and drug groups. The model and drug groups were inoculated with HSV-1 on the cornea of Balb/c mice using the corneal scratch method to construct an HSK mouse model, and the drug group was treated with Yinqiao Powder. The incidence and mortality of the three groups were compared on days 1, 3, 5, 7, and 14 after modeling.RESULTS:Compared with the control group, the HCE-T cell viability in the HSK group was decreased but apoptosis was increased, which was reversed by Yinqiao Powder intervention. Compared with the Ctrl group, the Arg-1 concentration in the cell supernatant of the HSV-1 group was decreased, the iNOS concentration was increased, and the protein expressions of cGAS, STING, and IRF3 were decreased. Compared with the HSV-1 group, the Arg-1 concentration was increased, the iNOS concentration was decreased, and the protein expressions of cGAS, STING, and IRF3 were enhanced in the HSV-1+oe-cGAS group and the HSV-1+Yinqiao Powder group, and the same results were obtained in the HSV-1+oe-cGAS+Yinqiao Powder group. Compared with the Ctrl-CM group, the HCE-T cell viability was decreased and apoptosis was increased in the HSV-1-CM group, which was reversed by overexpressing cGAS in macrophages or intervening with Yinqiao Powder. In vivo experiments found that Yinqiao Powder intervention could improve the pathological progression of keratitis.CONCLUSION:Yinqiao Powder inhibits M1 polarization of macrophages through the cGAS-STING-IRF3 molecular pathway, thereby delaying the progression of HSK.
2.Clinical Efficacy and Mechanism of Shengmai Jiuxin Decoction in Treating Chronic Heart Failure with Qi and Yin Deficiency, Yang Deficiency, and Blood Stasis
Yiming YAO ; Hongjun ZHU ; Yang ZHAO ; Man SHI ; Yujin GONG ; Yuan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):151-158
ObjectiveTo investigate the clinical efficacy and potential mechanism of Shengmai Jiuxin decoction in the treatment of acute decompensated heart failure (ADHF) with the traditional Chinese medicine (TCM) pattern of Qi and Yin deficiency, Yang deficiency, and blood stasis. MethodsA total of 68 patients diagnosed with ADHF of Qi and Yin deficiency, Yang deficiency, and blood stasis type were randomly assigned to an observation group (34 cases) and a control group (34 cases). Both groups received conventional Western medical treatment, while the observation group was additionally administered Shengmai Jiuxin decoction. Parameters compared before and after treatment included: TCM syndrome score, TCM syndrome efficacy, New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), six-minute walk distance (6MWD), hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor A (VEGF-A), Caspase-3, and the number of rehospitalizations for heart failure within one month after discharge. ResultsThere were no significant differences in sex, age, vital signs, or underlying diseases between the two groups. Compared with baseline, both groups exhibited significant reductions in TCM syndrome scores, NT-proBNP, and HIF-1α levels (P<0.01), as well as significant increases in 6MWD, LVEF, VEGF-A, and Caspase-3 levels (P<0.05, P<0.01). After treatment, the observation group showed significantly greater reductions in TCM syndrome score, NT-proBNP, HIF-1α, and Caspase-3 levels compared with the control group (P<0.05) and significantly greater increases in 6MWD, TCM syndrome efficacy, and VEGF-A levels (P<0.05). No significant differences were observed between the groups in NYHA functional classification, LVEF, or the number of rehospitalizations for heart failure within one month after discharge. No drug-related adverse events were reported in either group during the treatment period. ConclusionShengmai Jiuxin decoction can improve cardiac function and clinical symptoms in patients with ADHF of Qi and Yin deficiency, Yang deficiency, and blood stasis type. Its mechanisms may be related to the regulation of the HIF-1 signaling pathway by modulating targets such as HIF-1α, VEGF-A, and Caspase-3.
3.Clinical Efficacy and Mechanism of Shengmai Jiuxin Decoction in Treating Chronic Heart Failure with Qi and Yin Deficiency, Yang Deficiency, and Blood Stasis
Yiming YAO ; Hongjun ZHU ; Yang ZHAO ; Man SHI ; Yujin GONG ; Yuan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):151-158
ObjectiveTo investigate the clinical efficacy and potential mechanism of Shengmai Jiuxin decoction in the treatment of acute decompensated heart failure (ADHF) with the traditional Chinese medicine (TCM) pattern of Qi and Yin deficiency, Yang deficiency, and blood stasis. MethodsA total of 68 patients diagnosed with ADHF of Qi and Yin deficiency, Yang deficiency, and blood stasis type were randomly assigned to an observation group (34 cases) and a control group (34 cases). Both groups received conventional Western medical treatment, while the observation group was additionally administered Shengmai Jiuxin decoction. Parameters compared before and after treatment included: TCM syndrome score, TCM syndrome efficacy, New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), six-minute walk distance (6MWD), hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor A (VEGF-A), Caspase-3, and the number of rehospitalizations for heart failure within one month after discharge. ResultsThere were no significant differences in sex, age, vital signs, or underlying diseases between the two groups. Compared with baseline, both groups exhibited significant reductions in TCM syndrome scores, NT-proBNP, and HIF-1α levels (P<0.01), as well as significant increases in 6MWD, LVEF, VEGF-A, and Caspase-3 levels (P<0.05, P<0.01). After treatment, the observation group showed significantly greater reductions in TCM syndrome score, NT-proBNP, HIF-1α, and Caspase-3 levels compared with the control group (P<0.05) and significantly greater increases in 6MWD, TCM syndrome efficacy, and VEGF-A levels (P<0.05). No significant differences were observed between the groups in NYHA functional classification, LVEF, or the number of rehospitalizations for heart failure within one month after discharge. No drug-related adverse events were reported in either group during the treatment period. ConclusionShengmai Jiuxin decoction can improve cardiac function and clinical symptoms in patients with ADHF of Qi and Yin deficiency, Yang deficiency, and blood stasis type. Its mechanisms may be related to the regulation of the HIF-1 signaling pathway by modulating targets such as HIF-1α, VEGF-A, and Caspase-3.
4.Observation on the distribution of macular cone in healthy adult using adaptive optics scanning laser ophthalmoscope system
Yue ZHAO ; Tingting YANG ; Jin YAO
International Eye Science 2024;24(3):473-478
AIM: To observe the distribution of cone in the macular of healthy adult in different ages using adaptive optics scanning laser ophthalmoscope(AO-SLO)system, and analyze its relationship with age.METHODS: A total of 100 healthy examinees(200 eyes)in our hospital from June to July 2023 were selected, and they were divided into four groups according to their age, with 25 cases(50 eyes)in each group, including 18-30 years in group A, 31-40 years in group B, 41-50 years in group C, 51-65 years in group D. AO-SLO was performed in both eyes and cone density was measured.RESULTS: The density of cone in the foveal eccentricity of 3° and 2.4°×2.4° in each group was different(P<0.001), and the cone density in each area showed a relatively regular distribution characteristics, with the highest density in the temporal side, and the temporal>nasal>inferior>superior sides from high to low. The mean cone density in the macular area of both eyes was 14 144.38±1 082.40, 13 241.24±535.32, 12 930.29±727.73, and 10 907.50±490.86 cell/mm2, respectively(P<0.001), indicating that the cone density decreased with age. The correlation analysis showed that the mean cone density in the macular area was negatively correlated with age(r=-0.578, P<0.001).CONCLUSION: AO-SLO is a quantitative non-invasive detection of cones, and there is a negative correlation between cone density and age in healthy human. Furthermore, density of cone in healthy people over 50 years was significantly decreased.
5. Study on relationship of target organ injury of mechanism and "structure-effect-dose" of Hedysari Radix during radiotherapy-chemotherapy induced
Sha-Sha ZHAO ; Hai HE ; Zi-Yang WANG ; Yao-Ying XING ; Yuan REN ; Jing SHAO ; Sha-Sha ZHAO ; Hai HE ; Zi-Yang WANG ; Yao-Ying XING ; Jing SHAO ; Yuan REN ; Jing SHAO ; Jing SHAO
Chinese Pharmacological Bulletin 2024;40(2):371-380
Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "
6.Scutellarin inhibitting BV-2 microglia-mediated neuroinflammation via the cyclic GMP-AMP synthase-stimulator of interferon gene pathway
Zhao-Da DUAN ; Li YANG ; Hao-Lun CHEN ; Teng-Teng LIU ; Li-Yang ZHENG ; Dong-Yao XU ; Chun-Yun WU
Acta Anatomica Sinica 2024;55(2):133-142
Objective To explore the effect of scutellarin on lipopolysaccharide(LPS)induced neuroinflammation in BV-2 microglia cells.Methods BV-2 microglia were cultured and randomly divided into 6 groups:control group(Ctrl),cyclic GMP-AMP synthetase(cGAS)inhibitor RU320521 group(RU.521 group),LPS group,LPS+RU.521 group,LPS+scutellarin pretreatment group(LPS+S)and LPS+S+RU.521 group.The expressions of cGAS,stimulator of interferon gene(STING),nuclear factor kappa B(NF-κB),phosphorylated NF-κB(p-NF-κB),neuroinflammatory factors PYD domains-containing protein 3(NLRP3)and tumor necrosis factor α(TNF-α)in BV-2 microglia were detected by Western blotting and immunofluorescent double staining(n= 3).Results Western blotting and immunofluorescent double staining showed that compared with the control group,the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in BV-2 microglia increased significantly after LPS induction(P<0.05),while the expression of cGAS,STING,p-NF-κB,NLRP3 and TNF-α in LPS+S group were significantly lower than those in LPS group(P<0.05).Treatment with cGAS pathway inhibitor RU.521 showed similar effects as the pre-treatment group with scutellarin.In addition,the change of NF-κB in each group was not statistically significant(P>0.05).Conclusion Scutellarin inhibits the neuroinflammation mediated by BV-2 microglia cells,which may be related to cGAS-STING signaling pathway.
7.Intervention of muscle strength training combined with neuromuscular electrical stimulation on lower limb function and biomechanical changes in patients with patellofemoral pain
Jing WU ; Yingce YAO ; Xiaowei YANG ; Boshi XUE ; Jianbin ZHAO ; Chen YANG ; Tianfeng LUAN ; Zhipeng ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(9):1365-1371
BACKGROUND:Lower limb peri-knee muscle strength training and neuromuscular electrical stimulation are generally safe and effective rehabilitation methods for patellofemoral joint pain,but the mechanism of their intervention is still unclear. OBJECTIVE:To determine the effect of muscle strength training combined with neuromuscular electrical stimulation on pain,lower extremity function and biomechanical characteristics in patients with patellofemoral pain. METHODS:Thirty-seven patients with patellofemoral pain were randomly divided into muscle strength training combined with electrical stimulation group(trial group,n=19)and muscle strength training group(control group,n=18).Both groups underwent intervention training for 6 weeks,three times a week.The visual analog scale and anterior knee pain scale were used to evaluate the pain level and functional level of the knee.Kinematic and kinetics data during running were collected by using an infrared motion capture system and a three-dimensional force platform simultaneously.A two-way analysis of variance with repeated measures(group*time)was applied to analyze the data. RESULTS AND CONCLUSION:(1)After the intervention,the visual analog scale scores of the trial group and the control group were significantly decreased(P<0.001),and the anterior knee pain scale scores were significantly increased(Ptrial group<0.001,Pcontrol group=0.001)in the trial group and control group.The anterior knee pain scale scores of the trial group were significantly higher compared to the control group after the intervention(P=0.001).(2)The peak knee flexion angle(P=0.011),peak knee extension moment(P<0.001),the peak knee internal rotation moment(P=0.008),the peak patellofemoral stress(P<0.001)and the peak patellofemoral contact force(P<0.001)were significantly decreased in the trial and control groups during running after the intervention compared with those before the intervention.(3)In conclusion,both muscle strength training and muscle strength training combined with electrical stimulation training are helpful to improve the subjective pain and lower limb function of patellofemoral pain patients,enhance the movement pattern during running and reduce the stress of the patellofemoral joint.Compared with muscle strength training alone,muscle strength training combined with electrical stimulation can improve lower limb function more significantly.
8.Application of 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle
Lihang WANG ; Tingsheng LU ; Qiling CHEN ; Shudan YAO ; Xingwei PU ; Linsong JI ; Guoquan ZHAO ; Beiping OUYANG ; Bin ZHANG ; Zaisong YANG ; Chunshan LUO
Chinese Journal of Tissue Engineering Research 2024;28(18):2859-2864
BACKGROUND:The pedicle navigation template has many advantages,but there are still some problems.For example,poor soft tissue dissection leads to poor adhesion of the pedicle navigation template,resulting in screw path deviation;careful dissection of soft tissue to fit the pedicle navigation template leads to prolonged surgery time and increased bleeding;the design of the pedicle navigation template cannot predict the vertebral rotation and the impact of body position changes,resulting in the poor fitting. OBJECTIVE:To explore the utility of a new 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle. METHODS:A total of 20 patients with scoliosis and complicated pedicle admitted to the Department of Spinal Surgery,Guizhou Hospital,Beijing Jishuitan Hospital from February 2020 to February 2023 were selected for scoliosis orthopedics.During the operation,the 5-point positioning point-contact pedicle navigation template was used to guide the screws.According to the inclusion and exclusion criteria,34 cases were matched as the empirical nail placement group,and conventional barehanded nail placement was performed.The time of placement,the amount of bleeding,the number of fluoroscopies,the number of manual diversions,the level and accuracy of pedicle screws,the complications of placement,and the rate of correction of main curvature were compared between the two groups. RESULTS AND CONCLUSION:(1)There were no significant differences in sex,age,coronal Cobb's angle of the main curvature,bending Cobb's angle of the main curvature,pedicle variation,apex rotation,fusion segment,number of screws,level of screws,accuracy of screws,and rate of correction of main curvature between the navigation template group and the empirical nail placement group(P>0.05).(2)Compared with the empirical nail placement group,the navigation template group had more advantages in time of placement(P=0.034),amount of bleeding(P=0.036),number of fluoroscopies(P=0.000)and number of manual diversions(P=0.021).(3)There were 0 cases of screw-related complications in both groups.(4)In conclusion,the 5-point positioning point-contact 3D printing pedicle navigation template has a claw-like structure.It can firmly adapt to various deformities of the lamina articular process,avoid drift,and accurately place the screws.It has a point-like contact lamina structure to avoid extensive and complete dissection of the posterior structure,and reduce bleeding,operation time,and trauma.Pre-designed screw entry points and directions can reduce the number of fluoroscopy and operation time.Segmental design can avoid discomfort due to changes in anesthesia position.The operation is simple and the accuracy of screw placement is high.
9.Correlation between sagittal curvature parameters and pain threshold for neck-shoulder muscles in degenerative cervical spondylosis
Yunxiao YANG ; Chenglan HUANG ; Yutong HOU ; Yuan YAO ; Yu ZHAO ; Yuanjing XU ; Zezheng YANG ; Jinwu WANG
Chinese Journal of Tissue Engineering Research 2024;28(24):3879-3884
BACKGROUND:Patients with degenerative cervical spondylosis often suffer from changed varicosity of the cervical spine,unbalanced neck-shoulder muscular strength,and descending power. OBJECTIVE:To probe into the correlation between sagittal curvature parameters and pain threshold for neck-shoulder muscles in degenerative cervical spondylosis. METHODS:Totally 50 patients with degenerative cervical spondylosis received treatment at the 3D Printed Outpatient Center of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to March 2023 were included in the study.After excluding the 10 patients of cervical lateral projection that failed to meet the measurement conditions,the cervical lateral projections were shot to measure the following iconography parameters:Borden value and C2-7 Cobb angle as well as pain thresholds on the midpoint of the superior trapezius muscle in bilateral bundles and at 1 cm beside the C5-6 interspike.The correlation between sagittal curvature parameters and pain threshold of neck-shoulder muscles in degenerative cervical spondylosis was analyzed. RESULTS AND CONCLUSION:(1)The Borden value of sagittal curvature showed a moderately positive correlation with the bundle pain threshold in the left upper trapezius muscle,the bundle pain threshold in the right upper trapezius muscle,and the pain threshold at the 1 cm of the left side beside the C5-6 interspike(r=0.498,P<0.01;r=0.448,P<0.05;r=0.405,P<0.05)and a weak positive correlation with the pain threshold at the 1 cm of the right side beside the C5-6 interspike(r=0.322,P<0.05).(2)The C2-7 Cobb angle showed a weak positive correlation with the left squared myalgia threshold(r=0.355,P<0.05),and there was no correlation with the pain threshold of the left trapezius muscle and the pain threshold at the 1 cm of both sides beside the C5-6 interspike.(3)There was a correlation between the pain threshold of the neck-shoulder muscles,and a high correlation between the pain threshold of the left and right muscles and the pain threshold within the left and right side muscles,indicating that the neck-shoulder muscles are consistent and may be related to the coordination of the neck-shoulder movements.
10.Influence of PVE and PVE combined with TACE on secondary hepatectomy and prognosis of hepatocellular carcinoma
Junsheng NI ; Yao LI ; Xue LIU ; Guojun HOU ; Linghao ZHAO ; Yuan YANG ; Yefa YANG ; Weiping ZHOU
Chinese Journal of Digestive Surgery 2024;23(2):257-264
Objective:To investigate the influencing of portal vein embolization (PVE) and PVE combined with transcatheter arterial chemoembolization (TACE) on secondary hepatectomy and prognosis of patients with initially unresectable hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 102 patients with initially unresectable HCC who were admitted to the Third Affiliated Hospital of Naval Medical University from October 26,2015 to December 31,2022 were collected. There were 82 males and 20 females, aged 52(range,25?73)years. Of 102 patients, 72 cases undergoing PVE combined with TACE were set as the PVE+TACE group, and 30 cases undergoing PVE were set as the PVE group. Observation indicators: (1) surgical resection rate of secondary hepatectomy and increase of future liver remnant (FLR); (2) situations of secondary hepatectomy; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Surgical resection rate of secondary hepatectomy and increase of FLR. The surgical resection rate of secondary hepatectomy in the PVE+TACE group and the PVE group were 72.2%(52/72) and 53.3%(16/30), respectively, showing no significant difference between the two groups ( χ2=3.400, P>0.05). The surgical waiting time, increasing volume of FLR, growth rate of FLR in the 52 patients of PVE+TACE group receiving secon-dary hepatectomy were 20(range, 14?140)days, 140(range, 62?424)mL, 9.8(range, 1.5?26.5)mL/day, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 16(range, 12?35)days, 160(range, 95?408)mL, 10.5(range, 1.2?28.0)mL/day, respectively. There was no significant difference in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=1.830, 1.498, 1.266, P>0.05). (2) Situations of secondary hepatectomy. The operation time, rate of tumor necrosis (>90%, 60%?90%,<60%), cases with complications ≥ grade Ⅲa in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 200(range, 125?420)minutes, 8, 4, 40, 28, respectively. The above indicators in the 16 patients of PVE group receiving secondary hepatectomy were 170(range, 105?320)minutes, 0, 0, 16, 4, respectively. There were significant differences in the above indicators between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( Z=2.132, ?2.093, χ2=4.087, P<0.05). (3) Follow-up. Sixty-eight patients who completed the surgery were followed up for 40(range, 10?84)months. The 1-, 3-, 5-year recurrence free survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 73.0%, 53.3%, 35.4%, respectively. The above indicators in the 16 patients of PVE group were 62.5%, 37.5%, 18.8%, respectively. There was a significant difference in the recurrence free survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.035, P<0.05). The 1-, 3-, 5-year overall survival rate in the 52 patients of PVE+TACE group receiving secondary hepatectomy were 82.5%, 61.2%, 36.6%, respectively. The above indica-tors in the 16 patients of PVE group receiving secondary hepatectomy were 68.8%, 41.7%,20.8%, respectively. There was a significant difference in the overall survival rate between the 52 patients of PVE+TACE group and the 16 patients of PVE group ( χ2=4.767, P<0.05). Conclusion:Compared with PVE, PVE+TACE as stage Ⅰ surgery can increase the surgical resection rate of secondary hepatec-tomy and the recurrence free survival rate of patients with initially unresectable HCC, prolong the long-term survival time, but not influence the growth rate of FLR.

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