1.Tranexamic acid-fatty alcohol polyoxyethylene ether conjugation/PVA foam for venous sclerotherapy via vascular damage and inhibiting plasmin system.
Jizhuang MA ; Keda ZHANG ; Wenhan LI ; Yu DING ; Yongfeng CHEN ; Xiaoyu HUANG ; Tong YU ; Di SONG ; Haoran NIU ; Huichao XIE ; Tianzhi YANG ; Xiaoyun ZHAO ; Xinggang YANG ; Pingtian DING
Acta Pharmaceutica Sinica B 2025;15(6):3291-3304
Venous system diseases mainly include varicose veins and venous malformations of lower limbs and the genital system. Most of them are chronic diseases that cause serious clinical symptoms to patients and affect their health and quality of life. Sclerotherapy has become the first-line therapy for venous system diseases. However, there are problems such as incomplete fibrosis and vascular recanalization after sclerotherapy, and improper operation will cause serious adverse consequences. Therefore, exploring a safe and effective sclerotherapy strategy is essential for developing clinically successful sclerotherapy. To solve the above problems, we proposed a new sclerotherapy strategy with a dual mechanism of "vascular damage and plasmin (PLA) system inhibition." We intended to construct a novel cationic surfactant (AEOx-TA) by reacting tranexamic acid (TA), a parent structure, with fatty alcohol polyoxyethylene ether (AEOx) by ester bonds. AEOx-TA could damage vascular endothelium and initiate a coagulation cascade effect to induce thrombus. Furthermore, AEOx-TA could be degraded by esterase and release the parent drug, TA, which could inhibit the PLA system to inhibit the degradation of thrombus and extracellular matrix and promote the process of vascular fibrosis. In addition, such surfactant-based sclerosants have foam-forming properties, and they can be blended with polyvinyl alcohol (PVA) to prepare a highly stable foam formulation (AEOx-TA/P), which can achieve a precise drug delivery and prolonged drug retention time, thereby improving drug efficacy and reducing the risk of ectopic embolism. Overall, the novel cationic surfactant AEOx-TA provides a new avenue to resolve the bottleneck: surfactant sclerosants' efficiency is relatively low in the current sclerotherapy.
2.Effects of Xuebijing injection on gut microbiota and intestinal barrier in lipopolysaccharide-induced sepsis mice
Zhigang ZUO ; Liu PEI ; Yanmin ZHANG ; Tianzhi LIU ; Xiujuan LIU ; Xiaoyu LI ; Congcong ZHAO ; Zhenjie HU
Chinese Journal of Microbiology and Immunology 2025;45(7):548-559
Objective:To investigate the effects of Xuebijing injection on gut microbiota and intestinal mechanical barrier in mice with lipopolysaccharide (LPS)-induced sepsis, and analyze the potential mechanism by which Xuebijing injection protects gastrointestinal tract.Methods:Twenty-four healthy and clean grade male C57BL/6N mice were divided into four groups, control group, LPS group, LPS+ 5 μl/g Xuebijing injection group (5 μl/g Xuebijing injection group), and LPS+ 10 μl/g Xuebijing injection group (10 μl/g Xuebijing injection group), with six mice in each group. A mouse model of sepsis was established by intraperitoneal injection of mice with 10 μg/g LPS. At 0 and 12 h after successful modeling, the mice were intraperitoneally injected with 5 or 10 μl/g Xuebijing injection. Blood, ileum, and colon fecal samples were collected 12 h after the second administration. ELISA was used to detect the levels of diamine oxidase (DAO), D-blood lactic acid (D-Lac), TNF-α, and IL-6. HE staining was used to observe the local ileum damage, and Chiu′s score was used to evaluate the degree of intestinal tissue damage. Immunohistochemical staining and Western blot were used to detect the expression of Claudin-1, Occludin, and zona occludins-1(ZO-1) in ileum tissues, followed by semi quantitative analysis. One-way analysis of variance was used for intergroup comparisons, and LSD or Tamhane′s T2 test was used for pairwise comparisons based on the homogeneity of variance. The diversity and species composition of mouse fecal microbiota, and the differences among groups were analyzed using 16S rRNA sequencing.Results:The levels of DAO, D-Lac, TNF-α, and IL-6 in the LPS group were higher than those in the control group (all P<0.000 1). After the intervention with Xuebijing injection, the levels of DAO, D-Lac, TNF-α, and IL-6 decreased (all P<0.05) and showed no significant differences with those in the control group (all P>0.05). Besides, 10 μl/g Xuebijing injection was more effective than 5 μl/g Xuebijing injection in reducing the concentrations (all P<0.05). Chiu′s score was higher in the LPS group than in the control group and the 10 μl/g Xuebijing injection group (both P<0.05). Western blot showed that the expression levels of Occludin, Claudin-1, and ZO-1 in the LPS group were lower than those in the control group (all P<0.01), and Xuebijing injection intervention significantly increased the expression levels of these proteins in a dose-dependent manner as compared with the LPS group (all P<0.000 1). Apart from the expression level of ZO-1, which showed no significant difference between the two Xuebijing injection groups ( P>0.05), the results of immunohistochemical staining were consistent with those of Western blot. The 16S rRNA sequencing results showed that there were differences in the Alpha and Beta diversity indices, and the composition and structure of gut microbiota among the four groups. The structure of gut microbiota in the mice treated with Xuebijing injection was similar to that in the mice of the control group and it was in a dose-dependent manner. Wilcoxon rank sum test showed that there were statistically significant differences in six gut microbiota groups at the phylum level, and 32 gut microbiota groups at the genus level among the mice of four groups (all P<0.05). Conclusions:Xuebijing injection can provide protective effects on the gastrointestinal tract by protecting the structure of gut microbiota and intestinal barrier function, and the protective effect is somewhat correlated with the drug dosage.
3.Clinicopathological analysis and literature review of 7 cases of polymorphous low-grade neuroepithelial tumor of the young
Tianzhi ZHANG ; Dingzhun LIAO ; Li YUAN ; Cheng ZHI ; Wanming HU
Chinese Journal of Clinical and Experimental Pathology 2025;41(9):1180-1186
Purpose To explore the clinical and pathological characteristics,diagnostic features,differential diag-nosis,and prognosis of polymorphous low-grade neuroepithelial tumor of the young(PLNTY).Methods Clinical and imaging data from 7 patients with PLNTY were collected.Morphological evaluation was performed using HE staining.Immunohistochemistry with the EnVision method was used to detect the expression of including CD34,BRAF,IDH1,GFAP,Ki67,and other proteins.BRAF gene mutations were detected by real-time PCR,CDKN2A/B and 1p/19q co-deletion were assessed by FISH,and next-generation sequencing(NGS)was performed on selected cases.Results Among the seven patients,six were male and one was female,aged 8-29 years(median age:22 years).Tumors were located in the temporal lobe(5 cases),left insula and anterior temporal lobe(1 case),and frontotemporal lobe(1 case).Six patients had a history of epilepsy.Histologically,all tumors displayed oligodendroglioma-like areas.Two cases exhibited perivascular pseudorosette-like arrangements,and two showed focal cellular pleomorphism.Calcifica-tion and capillary networks were observed in all cases.Immunohistochemically,all tumors were positive for GFAP and Olig-2 and negative for IDH1(R132H).CD34 showed diffuse positivity in all cases.BRAF was positive in five cases.The Ki67 proliferation index ranged from 1%to 5%.Molecularly,all cases were IDH-wild type,with no 1p/19q co-deletion or CDKN2A/B deletion.BRAF V600E mutants were identified in five cases,and FGFR alterations in two.During follow-up(5-48 months),all patients survived;five remained recurrence-free,while two experienced recur-rence.Conclusion As a rare low-grade neuroepithelial tumor,clinicians and pathologists should master the diagnostic key points and differential diagnosis of PLNTY to avoid misdiagnosis and missed diagnosis.
4.Clinicopathological analysis and literature review of 7 cases of polymorphous low-grade neuroepithelial tumor of the young
Tianzhi ZHANG ; Dingzhun LIAO ; Li YUAN ; Cheng ZHI ; Wanming HU
Chinese Journal of Clinical and Experimental Pathology 2025;41(9):1180-1186
Purpose To explore the clinical and pathological characteristics,diagnostic features,differential diag-nosis,and prognosis of polymorphous low-grade neuroepithelial tumor of the young(PLNTY).Methods Clinical and imaging data from 7 patients with PLNTY were collected.Morphological evaluation was performed using HE staining.Immunohistochemistry with the EnVision method was used to detect the expression of including CD34,BRAF,IDH1,GFAP,Ki67,and other proteins.BRAF gene mutations were detected by real-time PCR,CDKN2A/B and 1p/19q co-deletion were assessed by FISH,and next-generation sequencing(NGS)was performed on selected cases.Results Among the seven patients,six were male and one was female,aged 8-29 years(median age:22 years).Tumors were located in the temporal lobe(5 cases),left insula and anterior temporal lobe(1 case),and frontotemporal lobe(1 case).Six patients had a history of epilepsy.Histologically,all tumors displayed oligodendroglioma-like areas.Two cases exhibited perivascular pseudorosette-like arrangements,and two showed focal cellular pleomorphism.Calcifica-tion and capillary networks were observed in all cases.Immunohistochemically,all tumors were positive for GFAP and Olig-2 and negative for IDH1(R132H).CD34 showed diffuse positivity in all cases.BRAF was positive in five cases.The Ki67 proliferation index ranged from 1%to 5%.Molecularly,all cases were IDH-wild type,with no 1p/19q co-deletion or CDKN2A/B deletion.BRAF V600E mutants were identified in five cases,and FGFR alterations in two.During follow-up(5-48 months),all patients survived;five remained recurrence-free,while two experienced recur-rence.Conclusion As a rare low-grade neuroepithelial tumor,clinicians and pathologists should master the diagnostic key points and differential diagnosis of PLNTY to avoid misdiagnosis and missed diagnosis.
5.Effects of Xuebijing injection on gut microbiota and intestinal barrier in lipopolysaccharide-induced sepsis mice
Zhigang ZUO ; Liu PEI ; Yanmin ZHANG ; Tianzhi LIU ; Xiujuan LIU ; Xiaoyu LI ; Congcong ZHAO ; Zhenjie HU
Chinese Journal of Microbiology and Immunology 2025;45(7):548-559
Objective:To investigate the effects of Xuebijing injection on gut microbiota and intestinal mechanical barrier in mice with lipopolysaccharide (LPS)-induced sepsis, and analyze the potential mechanism by which Xuebijing injection protects gastrointestinal tract.Methods:Twenty-four healthy and clean grade male C57BL/6N mice were divided into four groups, control group, LPS group, LPS+ 5 μl/g Xuebijing injection group (5 μl/g Xuebijing injection group), and LPS+ 10 μl/g Xuebijing injection group (10 μl/g Xuebijing injection group), with six mice in each group. A mouse model of sepsis was established by intraperitoneal injection of mice with 10 μg/g LPS. At 0 and 12 h after successful modeling, the mice were intraperitoneally injected with 5 or 10 μl/g Xuebijing injection. Blood, ileum, and colon fecal samples were collected 12 h after the second administration. ELISA was used to detect the levels of diamine oxidase (DAO), D-blood lactic acid (D-Lac), TNF-α, and IL-6. HE staining was used to observe the local ileum damage, and Chiu′s score was used to evaluate the degree of intestinal tissue damage. Immunohistochemical staining and Western blot were used to detect the expression of Claudin-1, Occludin, and zona occludins-1(ZO-1) in ileum tissues, followed by semi quantitative analysis. One-way analysis of variance was used for intergroup comparisons, and LSD or Tamhane′s T2 test was used for pairwise comparisons based on the homogeneity of variance. The diversity and species composition of mouse fecal microbiota, and the differences among groups were analyzed using 16S rRNA sequencing.Results:The levels of DAO, D-Lac, TNF-α, and IL-6 in the LPS group were higher than those in the control group (all P<0.000 1). After the intervention with Xuebijing injection, the levels of DAO, D-Lac, TNF-α, and IL-6 decreased (all P<0.05) and showed no significant differences with those in the control group (all P>0.05). Besides, 10 μl/g Xuebijing injection was more effective than 5 μl/g Xuebijing injection in reducing the concentrations (all P<0.05). Chiu′s score was higher in the LPS group than in the control group and the 10 μl/g Xuebijing injection group (both P<0.05). Western blot showed that the expression levels of Occludin, Claudin-1, and ZO-1 in the LPS group were lower than those in the control group (all P<0.01), and Xuebijing injection intervention significantly increased the expression levels of these proteins in a dose-dependent manner as compared with the LPS group (all P<0.000 1). Apart from the expression level of ZO-1, which showed no significant difference between the two Xuebijing injection groups ( P>0.05), the results of immunohistochemical staining were consistent with those of Western blot. The 16S rRNA sequencing results showed that there were differences in the Alpha and Beta diversity indices, and the composition and structure of gut microbiota among the four groups. The structure of gut microbiota in the mice treated with Xuebijing injection was similar to that in the mice of the control group and it was in a dose-dependent manner. Wilcoxon rank sum test showed that there were statistically significant differences in six gut microbiota groups at the phylum level, and 32 gut microbiota groups at the genus level among the mice of four groups (all P<0.05). Conclusions:Xuebijing injection can provide protective effects on the gastrointestinal tract by protecting the structure of gut microbiota and intestinal barrier function, and the protective effect is somewhat correlated with the drug dosage.
6.Gastrodin improves renal hypertension in rats possibly by inhibiting autophagy signals
Lifang SI ; Tianzhi ZHAO ; Yumin SONG ; Mengyun LI ; Xiang LI ; Feiyao WANG
Chinese Journal of Pharmacology and Toxicology 2024;38(5):369-374
OBJECTIVE To explore the mechanism by which gastrodin improves renal hyperten-sion in rats.METHODS A rat model of renal hypertension was established by ligating the renal artery.seventy-five rats were randomly divided into 5 groups(n=15):control group(sham operation group),model group,model+ramipril 1 mg·kg-1,model+gastrodin 100 and 200 mg·kg-1.The systolic blood pressure of the tail artery after modeling>18.12 kPa was regarded as the success of modeling.After the model was established,rats in the model+ramipril group were ig given ramipril 1 mg·kg-1 while the model+gastrodin group was ig given gastrodin 100 and 200 mg·kg-1 respectively for 4 weeks.Colori-metric assay kit was used to detect the serum superoxide dismutase(SOD)activity and malondialde-hyde(MDA)content in rats.ELISA was used to detect serum angiotensin-2(Ang-2)and aldosterone(ALD)contents,as well as serum and thoracic aortic tissue interleukin-1β(IL-1β),IL-6 and tumor necrosis factor α(TNF-α)content.HE staining was performed to detect pathological changes in thoracic aorta tissue of rats.The expressions of autophagy protein miceotubule associated protein light chain 3(LC3)-Ⅱand LC3-Ⅰwere detected by Western blotting.RESULTS The systolic pressure of the tail artery of rats after modeling exceeded 18.12 kPa,indicating that the modeling was successful.Compared with the control group,the contens of Ang-2(P<0.01)and ALD(P<0.01)in the model group were significantly increased,the activity of SOD(P<0.01)in serum and thoracic aorta tissue was significantly decreased,the content of MDA(P<0.01)was significantly increased,the contents of IL-1β,IL-6 and TNF-α in serum and thoracic aorta tissue were significantly decreased(P<0.01)and the ratio of LC-32/LC-31 in thoracic aorta tissue was significantly increased(P<0.01).Compared with the model group,gastrodin significantly increased the systolic pressure of the tail artery(P<0.01),the contents of Ang-2(P<0.01)and ALD(P<0.01)and the activity of SOD(P<0.01)in serum,as well as decreased the contents of MDA,IL-1β,IL-6 and TNF-α(P<0.01)in serum and thoracic aorta tissue.Meanwhile,gastrodin signifi-cantly decreased the ratio of LC3-Ⅱ/LC3-Ⅰ in rat thoracic aorta(P<0.01).CONCLUSION Gastrodin can improve the blood pressure of renal hypertensive rats,and the mechanism is possibly related to the reduction of autophagy protein LC3-Ⅱ/LC3-Ⅰratio.
7.A survey on clinical applications of transradial access for peripheral interventions in 2022
Xin ZHOU ; Minjie YANG ; Xiaoqian MENG ; Jiarui LI ; Yonghui HUANG ; Tianzhi AN ; Jian YOU ; Ersheng LI ; Wen ZHANG ; Zhiping YAN
Chinese Journal of Clinical Medicine 2024;31(3):440-444
Objective To investigate the current status,obstacles,and specific needs associated with the application of transradial access(TRA)in peripheral interventions in Chinese hospitals,with the aim of promoting the broader adoption of TRA in interventional procedures.Methods The Committee of Interventional Oncology of China Anti-Cancer Association conducted a cross-sectional questionnaire survey to investigate and analyze the nationwide situation of TRA in peripheral interventional surgeries in 2022.Results Personnel from 60 hospitals participated in the questionnaire.The results showed that the number of peripheral interventionals performed using TRA was significantly lower than that performed using transfemoral access(TFA),with considerable variability among hospitals.The primary obstacles to the adoption of TRA were the lack of suitable catheters and the difficulty of radial artery puncture.Approximately 86.67%of the institutions expressed a high expectation for the innovation of new TRA-specific devices,particularly catheters,microcatheters,and guidewires.60.00%of medical institutions indicated a strong desire for systematic training and participation in multi-center clinical trials.Conclusions TRA peripheral intervention is feasible in many hospitals in China,however,systematic training and further promotion of TRA are essential.The innovation of new TRA-specific devices and TRA in peripheral intervention is urgent.
8.Kehuang capsule inhibits MAPK and AKT signaling pathways to mitigate CCl4-induced acute liver injury
Qinyu NI ; Jiacheng LIN ; Weifan HUANG ; Liu YANG ; Ran LI ; Tianzhi TU ; Guangfu HE ; Yueqiu GAO ; Xuehua SUN ; Xiaoni KONG ; Xiaojun ZHU
Liver Research 2024;8(4):269-281
Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.
9.Quality Evaluation of Aurantii Fructus from Sichuan by Specific Chromatogram Combined with Chemometrics and Grey Correlation Analysis
Chunying RAN ; Jie WANG ; Yingxin CHEN ; Yanhong MA ; Lili YIN ; Haohan WANG ; Xiaoyang CAI ; Zhi LI ; Min LI ; Tianzhi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):121-127
ObjectiveHigh performance liquid chromatography (HPLC) was used to establish the specific chromatograms of Aurantii Fructus from different origins, and the quality variability of Aurantii Fructus from Sichuan was analyzed and evaluated by combining entropy weighting method and grey correlation method. MethodHPLC was performed on an Agilent Eclipse Plus C18 column (4.6 mm×250 mm, 5 μm) with a gradient elution of methanol (A)-0.1% phosphoric acid aqueous solution as the mobile phase (0-12 min, 25%-33%A; 12-21 min, 33%-41%A; 21-30 min, 41%-42%A; 30-40 min, 42%-59%A; 40-53 min, 59%-72%A; 53-60 min, 72%A; 60-65 min, 72%-100%A; 65-70 min, 100%A; 70~71 min, 100%-25%A; 71-80 min, 25% A) at a flow rate of 1.0 mL·min-1, the injection volume was 10 μL and the detection wavelength was 330 nm. Fifty batches of Aurantii Fructus samples from different origins (Sichuan, Chongqing, Jiangxi and Hunan) were tested, and the similarity evaluation software is used to generate characteristic profiles and compare them with control profile for peak identification, and then to evaluate the similarity of the samples. IBM SPSS 19.0 and SIMCA 14.1 were used to perform multivariate statistical analysis on the results of the samples, and then the entropy weighting method and grey correlation were used to calculate the overall quality score of samples from Sichuan. ResultHPLC specific chromatogram of Aurantii Fructus was established, and 14 common peaks were identified as eriocitrin, neoeriocitrin, narirutin, naringin, hesperidin, neohesperidin, meranzin hydrate, poncirin, meranzin, marmin, nobiletin, 3,3′,4′,5,6,7,8-heptamethoxyflavone, tangeretin and auraptene. And the similarities between the samples from Sichuan and the control chromatogram were all above 0.980. The samples could be classified into four categories according to their main origins by chemical pattern recognition, and the results of cluster analysis, principal component analysis and orthogonal partial least squares-discriminant analysis were all able to discriminate the samples of different main origins effectively. The comprehensive evaluation results of entropy weighting method combined with grey correlation showed that the quality of Aurantii Fructus from Sichuan varied greatly among different origins, and the quality of Aurantii Fructus from Sichuan was ranked as Bazhong>Luzhou>Chongqing>Neijiang. ConclusionIn this study, the characteristic mapping of Aurantii Fructus from Sichuan is established, and combined with the analytical methods of chemometrics and grey correlation, the quality of samples from different origins can be effectively differentiated, which can provide a reference for the comprehensive evaluation and control of the quality of Aurantii Fructus from Sichuan.
10.Working memory deficits in Parkinson's disease mouse model
Tingting ZHAO ; Huating GU ; Miao ZHAO ; Tianzhi CHEN ; Yingjie AN ; Xian ZHANG ; Jincan HOU ; Peng CAO ; Linghui ZENG ; Chengyu LI
Chinese Journal of Pharmacology and Toxicology 2023;37(7):517-518
OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.

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