1.Oral Herombopag Olamine and subcutaneous recombinant human thrombopoietin after haploidentical hematopoietic stem cell transplantation
Dai KONG ; Xinkai WANG ; Wenhui ZHANG ; Xiaohang PEI ; Cheng LIAN ; Xiaona NIU ; Honggang GUO ; Junwei NIU ; Zunmin ZHU ; Zhongwen LIU
Chinese Journal of Tissue Engineering Research 2025;29(1):1-7
BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an important treatment for malignant hematological diseases,and delayed postoperative platelet implantation is a common complication that seriously affects the quality of patient survival;however,there are no standard protocols to improve platelet implantation rates and prevent platelet implantation delays. OBJECTIVE:To compare the safety and efficacy of oral Herombopag Olamine versus subcutaneous recombinant human thrombopoietin for promoting platelet implantation in patients with malignant hematological diseases undergoing haploid hematopoietic stem cell transplantation. METHODS:Clinical data of 163 patients with malignant hematological diseases who underwent haploidentical hematopoietic stem cell transplantation from January 2016 to October 2022 were retrospectively analyzed.A total of 72 patients who started to subcutaneously inject recombinant human thrombopoietin at+2 days were categorized into the recombinant human thrombopoietin group;a total of 27 patients who started to orally take Herombopag Olamine at+2 days were categorized into the Herombopag Olamine group;and 64 patients who did not apply Herombopag Olamine or recombinant human thrombopoietin were categorized into the blank control group.The implantation status,incidence of acute graft-versus-host disease of degree II-IV within 100 days,1-year survival rate,1-year recurrence rate,and safety were analyzed in the three groups. RESULTS AND CONCLUSION:(1)The average follow-up time was 52(12-87)months.The implantation time of neutrophils in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group was(12.95±3.88)days,(14.04±3.71)days,and(13.89±2.74)days,respectively,with no statistically significant difference(P=0.352);the implantation time of platelets was(15.16±6.27)days,(17.67±6.52)days,and(17.00±4.75)days,with no statistically significant difference(P=0.287).(2)The complete platelet implantation rate on day 60 was 64.06%,90.28%,and 92.59%,respectively,and the difference was statistically significant(P<0.001).The subgroup analysis showed that the difference between the blank control group and the recombinant human thrombopoietin group was statistically significant(P<0.001),and the difference between the blank control group and the Herombopag Olamine group was statistically significant(P=0.004).The difference was not statistically significant between the recombinant human thrombopoietin group and Herombopag Olamine group(P=0.535).(3)100-day II-IV degree acute graft-versus-host disease incidence in the blank control group,recombinant human thrombopoietin group,and Herombopag Olamine group were 25.00%,30.56%,and 25.93%,respectively,and the difference was not statistically significant(P=0.752).(4)The incidence of cytomegalovirus anemia,cytomegalovirus pneumonia,and hepatic function injury had no statistical difference among the three groups(P>0.05).(5)During the follow-up period,there was no thrombotic event in any of the three groups of patients.(6)The results showed that recombinant human thrombopoietin and Herombopag Olamine could improve the platelet implantation rate of malignant hematological disease patients after haploidentical hematopoietic stem cell transplantation,with comparable efficacy and good safety.
2.The predictive value of CT pulmonary angiography combined with echocardiography for the degree of pulmonary hypertension
Ningli DONG ; Honggang YANG ; Huanhuan HEI ; Youmin GUO ; Xiaoyi DUAN ; Cong SHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(2):275-282
【Objective】 To compare the value of CT pulmonary angiography (CTPA) and echocardiography in predicting the degree pulmonary hypertension (PH). 【Methods】 Fifty-four patients in our hospital who underwent right heart catheterization, CTPA and echocardiography for suspected or confirmed PH from November 2013 to April 2021 were retrospectively recruited. Pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (PAMP) were measured by right heart catheterization. According to PAMP, the patients were divided into non-PH group and mild, moderate, and severe PH groups. The three-dimensional model of the pulmonary artery was obtained by computer-aided segmentation, and the best fitting circle diameter (Dfit), inscribed circle diameter (Dmin), circumscribed circle diameter (Dmax), hydraulic diameter (Dh), cross-sectional area (Area), circumference (Scf), and the largest area and largest short diameter of the right ventricle were measured. Echocardiography was used to estimate PASP. The differences in the above parameters between different PH groups were compared, the correlations of the above parameters with PASP and PAMP were analyzed, and statistically significant indicators were included to establish three predictive models of PAMP (Model 1: CTPA pulmonary artery; Model 2: CTPA pulmonary artery+CTPA right ventricle; Model 3: CTPA pulmonary artery+CTPA right ventricle+echocardiography), and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance of the three models. 【Results】 Some parameters of main pulmonary artery (Dfit, Dmin, Dmax, Dh, Area, Scf), right pulmonary artery (Dmax, Dh, Area, Scf), left pulmonary artery (Dfit), and right ventricular short diameter increased with the increase of PAMP (P<0.05). Dfit, Dmin, Dh, and area of main pulmonary artery, right pulmonary artery and left pulmonary artery were positively correlated with PASP and PAMP (P<0.05). Right ventricular short diameter and right ventricular maximum area were positively correlated with PASP (P<0.05), and right ventricular short diameter was positively correlated with PAMP (P<0.05). The estimated value of pulmonary artery systolic blood pressure in echocardiography was positively correlated with PASP and PAMP (P<0.05). Model 1, Model 2 and Model 3 could all be used to identify mild PH and moderate PH, among which Model 3 had the best performance in identifying non-PH and mild PH, moderate PH and severe PH. 【Conclusion】 CTPA and echocardiography are helpful in assessing the degree of PH, and the combination of the two has better accuracy in distinguishing non-PH from mild PH, moderate and severe PH.
3.Histological Characteristics of the Kidney in Mongolian Gerbils of Different Ages
Lingqun LU ; Honggang GUO ; Qiaojuan SHI ; Fangwei DAI ; Xiaofeng CHU
Laboratory Animal and Comparative Medicine 2023;43(1):61-66
ObjectiveTo explore the histological characteristics of the kidney in Mongolian gerbils of different ages. MethodsTen Mongolian gerbils of 2, 6, and 12 months old (half male and half female) were selected. After euthanasia, the kidneys were taken and paraffin sections were made. After HE, MASSON and PAS staining, the structural differences of different parts of the kidney tissue in gerbils of different ages were observed by digital scanning, and the relevant data of the kidney tissue were measured by image analysis software. ResultsThe number of proximal convoluted tubules was more than that of distal convoluted tubules in the renal cortex and outer medulla of gerbils. With age, the glomerular density decreased, the glomerular diameter increased, the basement membrane of renal tubules thickened, and the fibrous components between renal tubules increased. ConclusionThe histological structure of Mongolian gerbil's kidney varies with age, which may be related to glomerulosclerosis and parenchymal cell reduction. The specific mechanism needs further study.
4.Effects of cysteinyl leukotrienes receptor antagonists on chronic brain injury after global cerebral ischemia/reperfusion.
Hao WANG ; Honggang GUO ; Qi LOU ; Qiaojuan SHI
Journal of Zhejiang University. Medical sciences 2018;47(1):19-26
OBJECTIVE:
: To investigate the effects of cysteinyl leukotrienes receptor (CysLTR) antagonists on global cerebral ischemia/reperfusion (CI/R) injury in gerbils, and to explore its mechanism.
METHODS:
: Totally 40 gerbils weighting 45-65 g were randomized into sham, saline, Pranlukast and HAMI 3379 groups with 10 animals in each. The CI/R model was established in gerbils by bilateral common carotid occlusion for 10 min followed by reperfusion. After ischemia, the CysLTR antagonists Pranlukast (0.1 mg/kg) and HAMI 3379 (0.1 mg/kg) were injected intraperitoneally for 5 consecutive days in the last two groups,while the former two groups were injected with saline only (10 mL/kg). After 24 h or 14 d reperfusion, neurological deficit score was evaluated and the behavioral dysfunction was assessed, respectively. And 14 d after reperfusion, the neuron morphology of cerebral cortex was observed in brain sections stained with Cresyl violet. In addition, the Iba-1 (microgila) and GFAP (astrocyte) positive cells in cerebral cortex were observed by using immunohistochemitry method.
RESULTS:
: CI/R models were successfully established in 21 out of 30 gerbils with 7 in saline group, 6 in Pranlukast group, and 8 in HAMI 3379 group. Compared with saline group, Pranlukast and HAMI 3379 significantly attenuated neurological deficits, improved the behavioral function 24 h after reperfusion(all <0.01); Pranlukast and HAMI 3379 also significantly improved the behavioral function 14 days after reperfusion(<0.05 or <0.01). Compared with saline group, the neurological symptom scores in Pranlukast and HAMI 3379 groups presented a trend of amelioration 14 d after reperfusion, but it was not significant(>0.05). In addition, Pranlukast and HAMI 3379 also inhibited the neuron loss and injury, suppressed microgila and astrocyte activation 14 d after reperfusion(all <0.01).
CONCLUSIONS
: CysLTR antagonists Pranlukast and HAMI 3379 have long-term neuroprotective effect on chronic brain injury induced by global cerebral ischemia/reperfusion in gerbils.
Animals
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Behavior, Animal
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drug effects
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Brain Injury, Chronic
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drug therapy
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Brain Ischemia
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Gerbillinae
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Leukotriene Antagonists
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pharmacology
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therapeutic use
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Neuroprotective Agents
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pharmacology
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therapeutic use
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Random Allocation
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Receptors, Leukotriene
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metabolism
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Reperfusion Injury
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drug therapy
5.Cysteinyl leukotriene receptor antagonist alleviates global cerebral ischemia/reperfusion injury in gerbils through down?regulating autophagy
Qiaojuan SHI ; Honggang GUO ; Qi LOU ; Lingqun LU ; Ruozhen PAN ; Huazhong YING ; Wenwei ZHOU ; Xiaofeng CHU
Acta Laboratorium Animalis Scientia Sinica 2018;26(1):57-64
Objective Cysteinyl leukotrienes are potent inflammatory mediators. Their actions are mediated by specific receptors,the CysLT receptors(CysLT1R and CysLT2R),which have been cloned and characterized. In this stud-y,we investigated the protective effects of the CysLTR antagonist Pranlukast and HAMI 3379 on global cerebral ischemia/reperfusion(CI/R)injury in gerbils and its underlying mechanisms. Methods The gerbil model of CI/R was established by bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion. Then the animals were equally ran-domized into four groups: sham, model, Pranlukast(0.1 mg/kg)and HAMI 3379(0.1 mg/kg)groups. The later two groups were treated with intraperitoneal injection of Pranlukast and HAMI 3379,respectively,once daily for 4 days before carotid artery occlusion,while the former two groups with saline only,all at 10 mL/kg. After 24 h reperfusion,neurologi-cal deficit scores were observed and the behavioral dysfunction was assessed. The neuron morphology of cerebral cortex and CA1 subregion of hippocampus were observed in brain sections stained with cresyl violet. The expression of autophagy-relat-ed proteins beclin-1 and LC3 in the homogenate of cerebral cortex and hippocampus were determined using western blotting analysis. The ultrastructure of autophagosomes in the CA1 subregion of hippocampus was observed by electron microscopy. Results Compared with the model group, Pranlukast and HAMI 3379 attenuated neurological deficits, improved the be-havioral dysfunction,inhibited the neuron injury and loss, decreased the expression of autophagy-related protein beclin-1 and LC3 and the number of autophagosomes. Conclusions cysteinyl Leukotriene receptor antagonist Pranlukast and HAMI 3379 can alleviate global cerebral ischemia/reperfusion injury in gerbils. The protective effects of Pranlukast and HAMI 3379 appear to be associated with the inhibition of autophagy.
6.Berberine exerts pro-apoptotic effects on PC-9 cells via activation of JNK/FOXO3 signaling
LIU HONGGANG ; LAI YUANYANG ; ZHU YIFANG ; TONG LIPING ; DONG XIAOPING ; XU JUAN ; ZHANG YONG ; GUO HAIHUA ; LI XIAOFEI ; YAN XIAOLONG
Chinese Journal of Clinical Oncology 2017;44(17):846-850
Objective:To investigate the pro-apoptotic effect of berberine (Ber) on human lung adenocarcinoma PC-9 cell line, and to detect the role of c-Jun N-terminal kinase (JNK)/forkhead box protein O3 (FOXO3) signaling in this process. Methods:The PC-9 cells were randomly divided into the control group and the Ber group, which was treated with 30 and 60μM Ber. The survival rate, apoptot-ic rate, ROS generation, caspase-3 activity, and mitochondrial membrane potential of cells were detected. Western blot was per-formed to detect the expression of JNK/FOXO3 signaling and apoptosis-related proteins. A JNK-specific activation inhibitor, SP600125, was used to block the phosphorylation of FOXO3 in PC-9 cells, and then treated with Ber (30 and 60μM) for further detection after 24 h. Results:Ber treatment resulted in an obvious reduction in cell viability, promotion of cell apoptosis, downregulation of mitochondri-al membrane potential, and an increase of ROS and caspase-3 in a dose-dependent manner. Western blot analysis demonstrated that Ber treatment resulted in a significant upregulation of p-JNK, FOXO3, and Bax expression, and a downregulation of p-FOXO3 and Bcl2 levels. Moreover, the inhibition of JNK activation by SP600125 antagonized the anti-FOXO3 phosphorylation role and the pro-apoptotic role of Ber on PC-9 cells. Conclusion:Ber treatment effectively inhibits the viability of PC-9 cells and enhances apoptosis and oxidative stress injury, which may be related to the upregulation of p-JNK and FOXO3 and the downregulation of p-FOXO3.
7.Study on apoptosis of breast cancer cells induced by green tea
Chinese Journal of Primary Medicine and Pharmacy 2017;24(15):2371-2375
Objective To study the apoptosis of breast cancer cells induced by green tea and the preventive effect of green tea on cancer.Methods Catecholamine,the main components of green tea was added into human breast cancer cell line(MDA-MB-231) with different concentrations,and then human breast cancer cell line was measured by MTT assay,comet assay,flow cytometry and caspase-3 activity assay respectively.Results After treatment with 0.2mmol/L EGCG for 48 h,the cell proliferation was inhibited in the experimental group in MTT assay[minimum absorbance value (0.391±0.041),t=4.223 P<0.01].In comet assay,cells treated with 0.2mmol/L EGCG for 48 h in the experimental group showed a fairly long tail[control group average value (4.92±0.64)μm,the experimental group average value (18.76±1.37)μm,P=0.003].The rate of cell apoptosis increased significantly by testing MDA-MB-231 exposed to EGCG with flow cytometry.The apoptotic rate of the cells exposed to 0.2mmol/L EGCG for 48 h in the experimental group was (29.370±1.485)(t=11.125,P<0.01).EGCG induced apoptosis and caspase-3 activity rate was dependent on time and dose.The OD value of caspase-3 observed by the colorimetric method in cells exposed to 0.2mmol/L EGCG for 48 h in the experimental group was (0.144±0.045)(t=5.321,P<0.01).Conclusion EGCG may play a role in the treatment and prevention of breast cancer by affecting apoptosis.
8.Osteoporotic hip fractures in the elderly: yesterday, today and tomorrow
Chinese Journal of Tissue Engineering Research 2017;21(15):2438-2443
BACKGROUND: Senile hip fracture is a common disease, and its high disability and lethality severely affect the lifetime and quality of life of the elderly.OBJECTIVE: To summarize the research progress of senile osteoporotic hip fractures.METHODS: A computer-based search of CNKI, CqVip, WanFang and PubMed databases was performed for relevant basic research published from January 1995 to September 2016 using the keywords of osteoporosis,hip fracture, epidemiology in Chinese and English, respectively. Meanwhile, references in the searched articles were retrieved, finally 27 eligible articles were enrolled for analysis.RESULTS AND CONCLUSION: (1) The occurrence of senile osteoporotic hip fractures is closely related to the bone mineral density, proximal femur geometry, and fall-strain. (2) The preventions of osteoporotic fractures include primary prevention aiming at risk factors for osteoporosis and secondary prevention for osteoporotic patients. (3) The surgical treatment of femoral neck fracture is divided into open/closed reduction and internal fixation, femoral head arthroplasty and total hip arthroplasty. (4) Sliding hip screw fixation, proximal femoral intramedullary nail, external fixator and femoral head arthroplasty are used to treat intertrochanteric fracture. (5) There are various drugs used for hip fracture, such as calcium, vitamin D, estrogens, calcitonin and bisphosphonates. Indeed, individual treatment contributes to postoperative rehabilitation.
9.The experimental study on osteogenic potential of goat adipose derived stromal cells induced by PRP with rhBMP-2
Honggang GUO ; Fanglian YAO ; Tao WANG ; Yuzhu LIANG ; Shaoguang YANG ; Qiqing ZHANG ; Yongfa ZHENG
Chinese Journal of Microsurgery 2016;39(2):138-142
Objective To evaluate the feasibilty of modified osteogenic culturing of goat adipose derived stromal cells(ADSCs).Methods From March,2013 to September,2014,platelet-rich plasma(PRP) was made from goat autogenous vein blood,and abodimoneal fat was aspirated,following aspetic procedure,primary and series passage of ADSCs was established.Osteoinduced ADSCs was carried out according to following group:combinative osteoinduction group(PRP+rhBMP-2 +ADSCs),growth factor group(rhBMP-2+ADSCs),conventional inductive group(dexamathasone+ascorbic acid + ADSCs) and noninductive group(blank group).Converted microscope was used to observe cellular pattern,cell activity,osteocalcin and collagen type Ⅰ level were detected at 1,3,5,7,9,13,17,21 days.Red Alazarin and Von Kossa staining were also assayed at different interval.Results Under observation of converted microscopy,remarkable cell proliferation with abundant ECM was noticed in combinative osteoinduction group,compared with other groups,level of cell activity,osteocalcin,collagen type Ⅰ [(0.82 ± 2.19)AU,(79.82 ± 1.36)U/L at,(78.51 ± 4.32)μ g/ml at]were significantly higher than other groups (P <0.05),and remarkable ALP expression and calcifed nodules were also seen.Conclusion PRP can enhance the inductive effect of rhBMP-2,and combinative osteoinduction procedure acts as a satisfactory culturing method.
10.Establishment of a primary culture protocol of Mongolian gerbil hepatic stellate cells
Qi LOU ; Wei LI ; Qiaojuan SHI ; Lingqun LU ; Honggang GUO ; Jiangtao DU ; Xiaoying SA
Chinese Journal of Comparative Medicine 2016;26(3):29-34
Objective To investigate the method to isolate and culture hepatic stellate cells ( HSCs) for studying the cellular mechanisms of hepatic frbrosis.Methods HSCs were isolated by nycodenz density gradient centrifugation after the hepatocytes obtained from adult male gebils were digested with pronase, collagenase and DNase, infused via portal vein.The cell viability was determined by trypan blue exclusion test.The purity of HSCs was identified by detectingα-SMA, desmin immunohistochemical staining.Results The yield rate of HSCs was 0.5~1 ×107 per gerbil liver, and the cell viability was more than 90%.The percentage ofα-SMA-positive cells was more than 75%after 3 days primary culture and almost 100% cells were α-SMA and desmin positive in passage culture.Conclusion The successful protocol of primary culture of Mongolian gerbil HSC provide a technical support for research of relevant liver diseases and drug development in the future.

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