2.Impact of hydroxy-safflower yellow A on regeneration and repair capabilities of human umbilical cord mesenchymal stem cells
Yu-kang SUN ; Yan-zhe DUAN ; Jian-lin HUA ; Wei-hao JIA ; Jie-zhong YU ; Cun-gen MA ; Lei JIA ; Rui-ping ZHANG ; Xiao-yan ZHAI
Chinese Pharmacological Bulletin 2025;41(9):1643-1650
Aim To investigate the effects of hydroxyl-safflor yellow A(HSYA)on the regenerative and re-pair functions of human umbilical cord mesenchymal stem cells(hUC-MSCs).Methods hUC-MSCs were mechanically isolated,and their morphology was ob-served.Cell surface marker expression was analyzed u-sing flow cytometry.Osteogenic differentiation was used to confirm the multipotency of the cells.The cells were treated with various concentrations of HSYA(0,100,200,400,600 μmol·L-1),and the optimal con-centration and duration of treatment were determined u-sing the CCK-8 assay.Cells were divided into four groups:control,100,200,and 400 μmol·L-1.The proliferative capacity of hUC-MSCs was assessed by EdU incorporation.Vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BD-NF)levels in the culture supernatant were measured u-sing enzyme-linked immunosorbent assays.Cell migra-tion ability was evaluated by Scratch assays.The ex-pression levels of VEGF,BDNF,and fibroblast growth factor 2(FGF2)were detected by Western blotting.Results The isolated cells exhibited characteristics consistent with stem cell surface markers and demon-strated osteogenic and adipogenic differentiation poten-tial.After 48 hours of treatment,no cytotoxicity was observed at concentrations of 100,200,and 400 μmol·L-1compared to the control group.HSYA signifi-cantly increased the number of EdU-positive cells and cell migration rate,with the most pronounced effect was achieved at 200 μmol·L-1(P<0.01).VEGF and BDNF levels in the supernatant were elevated,with the highest expression observed at 200 μmol·L-1(P<0.01).Similarly,the expression levels of BDNF,VEGF,and FGF2 were significantly upregulated in the HSYA groups,with the highest levels at 200 μmol·L-1(P<0.01).Conclusion HSYA promotes the proliferation,migration and angiogenesis of hUC-MSCs,with an optimal concentration of 200 μmol·L-1.
3.Effect of tetramethylpyrazine on neuroinflammation after cerebral ischemia and hypoxia based on mannose-binding lectin
Yan-zhe DUAN ; Yu-kang SUN ; Jian-lin HUA ; Chun-li WEN ; Hao TIAN ; Yi YANG ; Xiu LOU ; Cun-gen MA ; Yu-qing YAN ; Li-juan SONG
Chinese Pharmacological Bulletin 2025;41(4):668-676
Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.
4.Effect of tetramethylpyrazine on neuroinflammation after cerebral ischemia and hypoxia based on mannose-binding lectin
Yan-zhe DUAN ; Yu-kang SUN ; Jian-lin HUA ; Chun-li WEN ; Hao TIAN ; Yi YANG ; Xiu LOU ; Cun-gen MA ; Yu-qing YAN ; Li-juan SONG
Chinese Pharmacological Bulletin 2025;41(4):668-676
Aim To investigate the effect of tetrameth-ylpyrazine(TMP)on neuroinflammation after cerebral ischemia and hypoxia via mannose-binding lectin(MBL).Methods Patients diagnosed with ischaemic stroke at Shanxi Provincial People's Hospital were in-cluded in the study,and their clinicopathological data,as well as blood and urine samples,were collected with the consent of the patients and their families.Using these biological samples,differential proteins and tar-gets were identified by proteomic analysis and subse-quently verified with animal experiments.The mice were divided into the sham,dMCAO,and TMP(10,20,40 mg·kg-1)treatment groups.After seven days of drug administration,the modified neurological sever-ity score(mNSS)was used to assess the neurological function.TTC staining was used to detect the volume of cerebral infarction.Motor function was evaluated be-haviourally,and ELISA was used to detect MASP1,sC5b-9,TNF-α,IL-6,and IL-1β.Western blot was used to determine the expression of relevant proteins,such as MBL2,MASP2,and C3.Results Compared with the sham group,the dMCAO group exhibited in-creased neurological impairment,which was signifi-cantly ameliorated by TMP treatment.The expression levels of MBL2,C3 and MASP2 were elevated in the dMCAO group and were reduced following TMP treat-ment.Additionally,the dMCAO group showed elevat-ed expression of inflammatory factors IL-1 β,IL-6 and TNF-α,which were then suppressed by TMP treat-ment.Conclusion TMP inhibits the inflammatory re-sponse after ischemia and hypoxia by regulating MBL,thus attenuating brain injury.
5.Impact of hydroxy-safflower yellow A on regeneration and repair capabilities of human umbilical cord mesenchymal stem cells
Yu-kang SUN ; Yan-zhe DUAN ; Jian-lin HUA ; Wei-hao JIA ; Jie-zhong YU ; Cun-gen MA ; Lei JIA ; Rui-ping ZHANG ; Xiao-yan ZHAI
Chinese Pharmacological Bulletin 2025;41(9):1643-1650
Aim To investigate the effects of hydroxyl-safflor yellow A(HSYA)on the regenerative and re-pair functions of human umbilical cord mesenchymal stem cells(hUC-MSCs).Methods hUC-MSCs were mechanically isolated,and their morphology was ob-served.Cell surface marker expression was analyzed u-sing flow cytometry.Osteogenic differentiation was used to confirm the multipotency of the cells.The cells were treated with various concentrations of HSYA(0,100,200,400,600 μmol·L-1),and the optimal con-centration and duration of treatment were determined u-sing the CCK-8 assay.Cells were divided into four groups:control,100,200,and 400 μmol·L-1.The proliferative capacity of hUC-MSCs was assessed by EdU incorporation.Vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BD-NF)levels in the culture supernatant were measured u-sing enzyme-linked immunosorbent assays.Cell migra-tion ability was evaluated by Scratch assays.The ex-pression levels of VEGF,BDNF,and fibroblast growth factor 2(FGF2)were detected by Western blotting.Results The isolated cells exhibited characteristics consistent with stem cell surface markers and demon-strated osteogenic and adipogenic differentiation poten-tial.After 48 hours of treatment,no cytotoxicity was observed at concentrations of 100,200,and 400 μmol·L-1compared to the control group.HSYA signifi-cantly increased the number of EdU-positive cells and cell migration rate,with the most pronounced effect was achieved at 200 μmol·L-1(P<0.01).VEGF and BDNF levels in the supernatant were elevated,with the highest expression observed at 200 μmol·L-1(P<0.01).Similarly,the expression levels of BDNF,VEGF,and FGF2 were significantly upregulated in the HSYA groups,with the highest levels at 200 μmol·L-1(P<0.01).Conclusion HSYA promotes the proliferation,migration and angiogenesis of hUC-MSCs,with an optimal concentration of 200 μmol·L-1.
6.Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study
Ding-Hua CHEN ; Chao-Fan LI ; Yue NIU ; Li ZHANG ; Yong WANG ; Zhe FENG ; Han-Yu ZHU ; Jian-Hui ZHOU ; Zhe-Yi DONG ; Shu-Wei DUAN ; Hong WANG ; Meng-Jie HUANG ; Yuan-Da WANG ; Shuo-Yuan CONG ; Sai PAN ; Jing ZHOU ; Xue-Feng SUN ; Guang-Yan CAI ; Ping LI ; Xiang-Mei CHEN
Chinese Journal of Infection Control 2024;23(3):257-264
Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P<0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P>0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P>0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.
7. Relationship between Fok polymorphism of vitamin-D receptor gene and hypertensive disorder complicating pregnancy in Han nationality of Qinghai province
Zhen WU ; Qian DUAN ; Ming YUAN ; Xue-Ni WANG ; Wen-Jing CHEN ; Jian-Hua LI ; Zhen WU ; Yu-Qin LI ; Yu-Qin E-LUO-JI
Acta Anatomica Sinica 2023;54(3):313-318
[ Abstract] Objective To investigate the relationship between single nucleotide polymorphism (SNP) Fok (rs2228570 / rs10735810) of vitamin D receptor (VDR) gene and hypertensive disorder complicating pregnancy (HDCP) in Han nationality women of Qinghai province. Methods A total of 137 Han nationality HDCP subjects (HDCP group) and 146 Han nationality normal pregnant subjects (control group) were selected from Qinghai province. The Fok polymorphism typing in HCDP group and control group was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The mutation was confirmed by sequencing. SPSS 19. 0 statistical software was used to test whether there were significant differences between two groups in general clinical data, genotype and allele frequency distribution. Results The frequency of FF Ff ff genotype of Fok in HDCP group and control group were 51. 82%, 37. 96%, 10. 22% and 34. 93%, 43. 15%, 21. 92% respectively (
8. Molecular analysis of interleukin 10 promoter region-592A/C polymorphism in hypertensive disorders of pregnancy in Qinghai Han nationality
Qian DUAN ; Jian-Hua LI ; Wen-Jia LI ; Ru WANG ; Zhen WU ; Ming YUAN
Acta Anatomica Sinica 2023;54(1):63-69
Objective To investigate the association between the interleukin 10 (IL-10) gene promoter region-592A/C (rs1800872) polymorphism and hypertensive disorders of pregnancy (HDP) in Han women of Qinghai province and to determine the expression of this gene in two groups (HDP group and healthy control group) preliminarily. Methods A total of 140 HDP patients (HDP group) and 140 normal pregnant women (control group) in Qinghai Province were selected. Using blood DNA as template, the IL-10-592A/C polymorphism typing of HDP group and control group was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified by sequencing. The expression of IL-10 mRNA in the placental tissues of the two groups was detected by Real-time PCR. Plasma IL-10 levels of the two groups were detected by ELISA. Results The frequencies of AA, AC and CC genotypes of IL-10 gene in HDP group and control group were 24. 29%, 44. 29%, 31. 42% and 13. 57%, 41. 43%, 45. 00% respectively, the difference in genotype distribution between the two groups was statistically significant (P<0. 05);AA genotype frequency in HDP group(24. 29%)was higher than that of control group(13. 57%)(P<0. 05), CC genotype frequency in HDP group (31. 42%) was lower than that in control group (45. 00%) (P < 0. 05), while there was no significant difference in genotype frequency of AC between the two groups (P<0. 05); The distribution of A and C allele frequencies of IL-10592A/C polymorphism was different between the two groups, and the A allele frequency of HDP group was higher than that of control group (
9.Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma.
Yingqiang LIU ; Zhengsheng ZHAN ; Zhuang KANG ; Mengyuan LI ; Yongcong LV ; Shenglan LI ; Linjiang TONG ; Fang FENG ; Yan LI ; Mengge ZHANG ; Yaping XUE ; Yi CHEN ; Tao ZHANG ; Peiran SONG ; Yi SU ; Yanyan SHEN ; Yiming SUN ; Xinying YANG ; Yi CHEN ; Shanyan YAO ; Hanyu YANG ; Caixia WANG ; Meiyu GENG ; Wenbin LI ; Wenhu DUAN ; Hua XIE ; Jian DING
Acta Pharmaceutica Sinica B 2023;13(12):4748-4764
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).
10.Clinical efficacy of da Vinci Xi robotic surgical system assisted pylorus and vagus preser-ving partial gastrectomy for early gastric cancer
Yichuan FAN ; Chi ZHANG ; Maohua WEI ; Hua ZHONG ; Haitao DUAN ; Weifeng SUN ; Liang CAO ; Jian ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of Digestive Surgery 2023;22(8):1014-1020
Objective:To investigate the clinical efficacy of da Vinci Xi robotic surgical system assisted pylorus and vagus preserving partial gastrectomy (RaPPG) for early gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 40 patients with early gastric cancer who were admitted to the First Affiliated Hospital of Dalian Medical University from December 2020 to November 2022 were collected. There were 26 males and 14 females, aged (64±8)years. Of the 40 patients, 19 patients undergoing da Vinci Xi RaPPG were divided into the robotic assisted group, and 21 patients undergoing laparoscopic assisted pylorus and vagus preserving partial gastrectomy (PPG) were divided into the laparoscopic control group. Observation indicators: (1) surgical situations; (2) postoperative complications; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or 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 rank sum test. Results:(1) Surgical situations. All patients in the two groups underwent surgery successfully, without conversion to laparotomy. The operation time, volume of intraoperative blood loss, time to postoperative first flatus, time to postoperative first liquid food intake, time to post-operative drainage tube removal, duration of postoperative hospital stay, tumor diameter, distance from distal resection margin to tumor were (298±52)minutes, 10(10, 10)mL, 3.0(3.0, 3.0)days, 3.0(3.0,4.0)days, 6.0(6.0,8.0)days, 7.0(6.0,8.0)days, (2.3±0.7)cm, 3.0(2.0,3.0)cm in patients of the robotic assisted group, versus (236±37)minutes, 25(15,50)mL, 5.0(4.0,5.0)days, 6.0(5.5,7.0)days, 8.0(8.0,9.5)days, 8.0(7.5,9.5)days, (2.9±1.1)cm ,2.0(1.5,2.0)cm in patients of the laparoscopic control group, showing significant differences in the above indicators between the two groups ( t=4.41, Z=-3.38, -4.75, -4.38, -2.98, -2.58, t=-2.10, Z=-3.03, P<0.05). (2) Postoperative complications. Cases with postoperative complications, cases with delayed gastric emptying, cases with acid regurgita-tion, cases with atelectasis, cases with infection of incision, cases with hyperamylasemia, cases with uroschesis were 6, 1, 1, 0, 1, 3, 0 in patients of the robotic assisted group. The above indicators were 20, 4, 3, 2, 1, 9, 1 in patients of the laparoscopic control group. There was a significant difference in the postoperative complications between the two groups ( χ2=17.77, P<0.05). (3) Follow-up. Of the 40 patients, 34 patients were followed up. There were 16 patients in the robotic assisted group who were followed up for 9(range, 6-18)months, and there were 18 patients in the laparoscopic control group who were followed up for 16(range, 9-23)months. During the follow-up period, all patients had good anastomosis healing, pyloric contraction function, and gastric emptying function. Conclusions:da Vinci Xi RaPPG is safe and feasible for the treatment of early gastric cancer. Compared with laparoscopic assisted PPG, treatment of gastric cancer with da Vinci Xi RaPPG can significantly reduce the volume of intraoperative blood loss, shorten the time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative drainage tube removal, duration of postoperative hospital stay, benefit the distance from distal resection margin to tumor, and reduce the incidence of postoperative complications.

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