1.Efficacy and safety of avatrombopag in the treatment of thrombocytopenia after umbilical cord blood transplantation.
Aijie HUANG ; Guangyu SUN ; Baolin TANG ; Yongsheng HAN ; Xiang WAN ; Wen YAO ; Kaidi SONG ; Yaxin CHENG ; Weiwei WU ; Meijuan TU ; Yue WU ; Tianzhong PAN ; Xiaoyu ZHU
Chinese Medical Journal 2025;138(9):1072-1083
BACKGROUND:
Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
METHODS:
We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation.
RESULTS:
Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z = 2.095, P = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P = 0.003).
CONCLUSION
Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans
;
Female
;
Male
;
Thrombocytopenia/etiology*
;
Adult
;
Retrospective Studies
;
Cord Blood Stem Cell Transplantation/adverse effects*
;
Middle Aged
;
Adolescent
;
Young Adult
;
Thiazoles/adverse effects*
;
Platelet Count
;
Receptors, Thrombopoietin/agonists*
;
Child
;
Thiophenes
2.Avatrombopag for platelet engraftment after allogeneic hematopoietic stem cell transplantation in children: a retrospective clinical study.
Xin WANG ; Yuan-Yuan REN ; Xia CHEN ; Chao-Qian JIANG ; Ran-Ran ZHANG ; Xiao-Yan ZHANG ; Li-Peng LIU ; Yu-Mei CHEN ; Li ZHANG ; Yao ZOU ; Fang LIU ; Xiao-Juan CHEN ; Wen-Yu YANG ; Xiao-Fan ZHU ; Ye GUO
Chinese Journal of Contemporary Pediatrics 2025;27(10):1233-1239
OBJECTIVES:
To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO).
METHODS:
A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38).
RESULTS:
At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043).
CONCLUSIONS
In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans
;
Retrospective Studies
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Male
;
Female
;
Child
;
Child, Preschool
;
Infant
;
Adolescent
;
Transplantation, Homologous
;
Blood Platelets/drug effects*
;
Thiazoles/therapeutic use*
;
Thrombopoietin/therapeutic use*
;
Thiophenes
3.The Efficacy of Combination of Avatrombopag and rhIL-11 in Adult Patients of Acute Myeloid Leukemia with Cancer Treatment-Induced Thrombocytopenia.
Min-Na LUO ; Hai-Tao ZHANG ; Si-Jie ZHAO ; Jing LI ; Wen-Juan WANG ; Peng-Cheng HE
Journal of Experimental Hematology 2025;33(3):848-852
OBJECTIVE:
To investigate the safety and efficacy of avatrombopag(AVA) combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia.
METHODS:
The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups.
RESULTS:
D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups.
CONCLUSION
The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.
Humans
;
Leukemia, Myeloid, Acute/drug therapy*
;
Thrombocytopenia/chemically induced*
;
Interleukin-11/therapeutic use*
;
Retrospective Studies
;
Adult
;
Thiophenes/therapeutic use*
;
Platelet Count
;
Female
;
Male
;
Middle Aged
;
Thiazoles
4.Efficacy Analysis of Stanozolol Combined with Avatrombopag in the Treatment of Chemotherapy-Induced Thrombocytopenia in Relapsed/Refractory Tumors.
Yan HE ; Wei-Yi LIU ; Yan-Yu ZHANG ; Yan LYU ; Shan-Shan ZHANG ; Ri-Cheng QUAN
Journal of Experimental Hematology 2025;33(4):1127-1130
OBJECTIVE:
To investigate the efficacy and safety of stanozolol combined with avatrombopag in the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with relapsed/refractory tumors.
METHODS:
Twenty-five patients with relapsed/refractory CIT admitted to the Hematology Department of Xiyuan Hospital, China Academy of Chinese Medical Sciences between March 2023 to December 2023 were enrolled. These patients received a combined therapy of stanozolol and avatrombopag. The clinical efficacy, onset time, changes in platelet levels and blood cell counts before and after treatment, and adverse reactions of patients were evaluated.
RESULTS:
The combination therapy demonstrated remarkable efficacy with a total effective rate of 100%. Among the 25 patients, 19 achieved complete remission and 6 achieved partial remission. The median onset time was 42.5(range: 35-48)days. The average platelet count of the 25 patients increased from (25.73±17.75)×109/L before treatment to (146.4±49.59)×109/L after 3 months of treatment, with a statistically significant difference ( P < 0.05). 18 patients who previously required platelet transfusion were all weaned off platelet transfusion after 3 months of treatment, with a median time to be free from platelet transfusion was 26 (range: 18-51) days. During the treatment, both neutrophils and hemoglobin exhibited various degrees of elevation. Two patients experienced a slight increase in alanine aminotransferase(ALT) levels, which normalized after treatment with oral hepatoprotective drug. One patient had a PLT increase exceeding 350×109/L, and the treatment with avatrombopag was suspended, and aspirin and other drugs were given to prevent thrombosis. No thrombose events or CIT-related bleeding events were observed in all patients.
CONCLUSION
The combination therapy of stanozolol and avatrombopag is significantly effective for treating relapsed/refractory CIT patients, with a high response rate and good safety, making it a suitable clinical treatment option.
Humans
;
Thrombocytopenia/chemically induced*
;
Stanozolol/therapeutic use*
;
Male
;
Female
;
Neoplasms/drug therapy*
;
Middle Aged
;
Thiophenes/therapeutic use*
;
Adult
;
Platelet Count
;
Treatment Outcome
;
Antineoplastic Agents/adverse effects*
;
Recurrence
;
Thiazoles
5.Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy.
Xiao Lin JIANG ; Xin YAN ; Hui Na SU ; Yan Hua LIU ; Ru Xue HAN ; Zi Yi SONG ; Xiao Wan SUN ; De Hui SU ; Xin YANG
Chinese Journal of Obstetrics and Gynecology 2023;58(4):286-292
Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.
Female
;
Humans
;
Adult
;
Menorrhagia/etiology*
;
Fibrinolytic Agents/adverse effects*
;
Levonorgestrel/adverse effects*
;
Amenorrhea/drug therapy*
;
Mifepristone/therapeutic use*
;
Quality of Life
;
Rivaroxaban/therapeutic use*
;
Hemoglobins
;
Intrauterine Devices, Medicated/adverse effects*
;
Contraceptive Agents, Female
6.Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty: a randomized controlled trial.
Can ZHANG ; Ying-Fei SHEN ; Shang-Ju XIE ; Ren-Fu QUAN
Chinese Acupuncture & Moxibustion 2023;43(2):144-148
OBJECTIVE:
To investigate the clinical effect of aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban for lower extremity venous thrombosis after total knee arthroplasty and the influence on hypercoagulation.
METHODS:
Seventy-three patients of knee osteoarthritis with lower extremity venous thrombosis after total knee arthroplasty (KOA) were randomly divided into an observation group (37 cases, 2 cases dropped off) and a control group (36 cases, 1 case dropped off). The patients in the control group took orally rivaroxaban tablets, 10 mg a time, once a day. On the basis of the treatment as the control group, the aconite-isolated moxibustion was applied to Yongquan (KI 1) for the patients of the observation group, once daily and 3 moxa cones were used in each treatment. The duration of treatment was 14 days in both groups. Before treatment and 14 days into treatment, the ultrasonic B test was adopted to determine the conditions of lower extremity venous thrombosis in the two groups. Before treatment, 7 and 14 days into treatment, the coagulation indexes (platelet [PLT], prothrombin time [PT], activated partial prothrombin time [APTT], fibrinogen [Fib] and D-dimer[D-D]), the blood flow velocity of the deep femoral vein and the circumference of the affected side were compared between the two groups separately, and the clinical effect was evaluated.
RESULTS:
Fourteen days into treatment, the venous thrombosis of the lower extremity was relieved in both groups (P<0.05), and that of the observation group was better than the control group (P<0.05). Seven days into treatment, the blood flow velocity of the deep femoral vein was increased compared with that before treatment in the observation group (P<0.05), and the blood flow rate in the observation group was higher than that in the control group (P<0.05). Fourteen days into treatment, PT, APTT and the blood flow velocity of the deep femoral vein were increased in the two groups compared with those before treatment (P<0.05); and PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all reduced in the two groups (P<0.05). Compared with the control group 14 days into treatment, the blood flow velocity of the deep femoral vein was higher (P<0.05), PLT, Fib, D-D and the circumference of the limb (knee joint, 10 cm above the patella and 10 cm below the patella) were all lower in the observation group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 85.7% (30/35) in the control group (P<0.05).
CONCLUSION
Aconite-isolated moxibustion at Yongquan (KI 1) combined with rivaroxaban can effectively treat lower extremity venous thrombosis after total knee arthroplasty, relieve hypercoagulation, accelerate the blood flow velocity and alleviate swelling of the lower extremity in the patients with knee osteoarthritis.
Humans
;
Rivaroxaban
;
Arthroplasty, Replacement, Knee
;
Moxibustion
;
Aconitum
;
Osteoarthritis, Knee/therapy*
;
Venous Thrombosis/surgery*
;
Lower Extremity
7.Safety and efficacy of combined antiplatelet and low-dose rivaroxaban in patients with chronic limb threatening ischaemia in Singapore.
Claire Alexandra CHEW ; Julian Chi Leung WONG ; Charyl Jia Qi YAP ; Shereen Xue Yun SOON ; Tjun Yip TANG
Annals of the Academy of Medicine, Singapore 2022;51(9):580-582
8.Effect of electroacupuncture at "Zusanli" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia.
Jia-Zi DONG ; Pei-Jing RONG ; Xiao-Tong WANG ; Dan WANG ; Ming-Hui LENG ; Lu-Jia XIAO
Chinese Acupuncture & Moxibustion 2022;42(7):767-772
OBJECTIVE:
To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD).
METHODS:
Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg-1•d-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA.
RESULTS:
Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01).
CONCLUSION
EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.
Acupuncture Points
;
Animals
;
Duodenum/metabolism*
;
Dyspepsia/therapy*
;
Electroacupuncture
;
Ketotifen
;
Mast Cells/metabolism*
;
Nerve Growth Factor/metabolism*
;
RNA, Messenger
;
Rats
;
Rats, Sprague-Dawley
;
Receptor, trkA/genetics*
9.Investigation on the growth factor regulatory network of dermal fibroblasts in mouse full-thickness skin defect wounds based on single-cell RNA sequencing.
Li Xiang SUN ; Shuai WU ; Xiao Wei ZHANG ; Wen Jie LIU ; Ling Juan ZHANG
Chinese Journal of Burns 2022;38(7):629-639
Objective: To explore the heterogeneity and growth factor regulatory network of dermal fibroblasts (dFbs) in mouse full-thickness skin defect wounds based on single-cell RNA sequencing. Methods: The experimental research methods were adopted. The normal skin tissue from 5 healthy 8-week-old male C57BL/6 mice (the same mouse age, sex, and strain below) was harvested, and the wound tissue of another 5 mice with full-thickness skin defect on the back was harvested on post injury day (PID) 7. The cell suspension was obtained by digesting the tissue with collagenase D and DNase Ⅰ, sequencing library was constructed using 10x Genomics platform, and single-cell RNA sequencing was performed by Illumina Novaseq6000 sequencer. The gene expression matrices of cells in the two kinds of tissue were obtained by analysis of Seurat 3.0 program of software R4.1.1, and two-dimensional tSNE plots classified by cell group, cell source, and gene labeling of major cells in skin were used for visual display. According to the existing literature and the CellMarker database searching, the expression of marker genes in the gene expression matrices of cells in the two kinds of tissue was analyzed, and each cell group was numbered and defined. The gene expression matrices and cell clustering information were introduced into CellChat 1.1.3 program of software R4.1.1 to analyze the intercellular communication in the two kinds of tissue and the intercellular communication involving vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) signal pathways in the wound tissue, the relative contribution of each pair of FGF subtypes and FGF receptor (FGFR) subtypes (hereinafter referred to as FGF ligand receptor pairs) to FGF signal network in the two kinds of tissue, and the intercellular communication in the signal pathway of FGF ligand receptor pairs with the top 2 relative contributions in the two kinds of tissue. The normal skin tissue from one healthy mouse was harvested, and the wound tissue of one mouse with full-thickness skin defect on the back was harvested on PID 7. The multiple immunofluorescence staining was performed to detect the expression and distribution of FGF7 protein and its co-localized expression with dipeptidyl peptidase 4 (DPP4), stem cell antigen 1 (SCA1), smooth muscle actin (SMA), and PDGF receptor α (PDGFRα) protein. Results: Both the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7 contained 25 cell groups, but the numbers of cells in each cell group between the two kinds of tissue were different. Genes PDGFRα, platelet endothelial cell adhesion molecule 1, lymphatic endothelial hyaluronic acid receptor 1, receptor protein tyrosine phosphatase C, keratin 10, and keratin 79 all had distinct distributions on two-dimensional tSNE plots, indicating specific cell groups respectively. The 25 cell groups were numbered by C0-C24 and divided into 9 dFb subgroups and 16 non-dFb groups. dFb subgroups included C0 as interstitial progenitor cells, C5 as adipose precursor cells, and C13 as contractile muscle cells related fibroblasts, etc. Non-dFb group included C3 as neutrophils, C8 as T cells, and C18 as erythrocytes, etc. Compared with that of the normal skin tissue of healthy mice, the intercellular communication in the wound tissue of full-thickness skin defected mice on PID 7 was more and denser, and the top 3 cell groups in intercellular communication intensity were dFb subgroups C0, C1, and C2, of which all communicated with other cell groups in the wound tissue. In the wound tissue of full-thickness skin defected mice on PID 7, VEGF signals were mainly sent by the dFb subgroup C0 and received by vascular related cell groups C19 and C21, PDGF signals were mainly sent by peripheral cells C14 and received by multiple dFb subgroups, EGF signals were mainly sent by keratinocyte subgroups C9 and C11 and received by the dFb subgroup C0, and the main sender and receiver of FGF signals were the dFb subgroup C6. In the relative contribution rank of FGF ligand receptor pairs to FGF signal network in the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7, FGF7-FGFR1 was the top 1, and FGF7-FGFR2 or FGF10-FGFR1 was in the second place, respectively; compared with those in the normal skin tissue, there was more intercellular communication in FGF7-FGFR1 signal pathway, while the intercellular communication in FGF7-FGFR2 and FGF10-FGFR1 signal pathways decreased slightly or did not change significantly in the wound tissue; the intercellular communication in FGF7-FGFR1 signal pathway in the wound tissue was stronger than that in FGF7-FGFR2 or FGF10-FGFR1 signal pathway; in the two kinds of tissue, FGF7 signal was mainly sent by dFb subgroups C0, C1, and C2, and received by dFb subgroups C6 and C7. Compared with that in the normal skin tissue of healthy mouse, the expression of FGF7 protein was higher in the wound tissue of full-thickness skin defected mouse on PID 7; in the normal skin tissue, FGF7 protein was mainly expressed in the skin interstitium and also expressed in the white adipose tissue near the dermis layer; in the two kinds of tissue, FGF7 protein was co-localized with DPP4 and SCA1 proteins and expressed in the skin interstitium, co-localized with PDGFRα protein and expressed in dFbs, but was not co-localized with SMA protein, with more co-localized expression of FGF7 in the wound tissue than that in the normal skin tissue. Conclusions: In the process of wound healing of mouse full-thickness skin defect wound, dFbs are highly heterogeneous, act as potential major secretory or receiving cell populations of a variety of growth factors, and have a close and complex relationship with the growth factor signal pathways. FGF7-FGFR1 signal pathway is the main FGF signal pathway in the process of wound healing, which targets and regulates multiple dFb subgroups.
Animals
;
Dipeptidyl Peptidase 4
;
Epidermal Growth Factor
;
Fibroblasts
;
Imidazoles
;
Ligands
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Receptor, Platelet-Derived Growth Factor alpha
;
Sequence Analysis, RNA
;
Skin Abnormalities
;
Soft Tissue Injuries
;
Spinocerebellar Ataxias
;
Sulfonamides
;
Thiophenes
;
Vascular Endothelial Growth Factor A
10.Safety of early surgery for geriatric hip fracture patients taking clopidogrel: a retrospective case-control study of 120 patients in China.
Ming-Hui YANG ; Bo LI ; Dong-Chen YAO ; Yan ZHOU ; Wen-Chao ZHANG ; Geng WANG ; Ping ZHANG ; Shi-Wen ZHU ; Xin-Bao WU
Chinese Medical Journal 2021;134(14):1720-1725
BACKGROUND:
Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal.
METHODS:
Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued <5 days before surgery constituted the clopidogrel group. The control group constituted 60 patients not taking antiplatelet or anticoagulant drugs and matched 1:1 with the clopidogrel group for sex, fracture type, operative procedure, and time from injury to operation (±10 h). The primary outcome was perioperative blood loss and the secondary outcomes were transfusion requirement, complications, and mortality. The Student's t test or Wilcoxon signed rank sum test was used for continuous variables and the Chi-square test was used for categorical variables.
RESULTS:
Age, body mass index, American Society of Anesthesiologists score, and percentage undergoing general anesthesia were comparable between the groups (P > 0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P < 0.001) and cerebrovascular disease (45.0% vs. 15.0%; P < 0.010) were significantly higher in the clopidogrel vs. control groups, respectively. The median clopidogrel discontinuation time before operation was 73.0 (range: 3.0-120.0) h. There was no significant difference in the estimated perioperative blood loss between the clopidogrel group (median: 745 mL) and control group (median: 772 mL) (P = 0.866). The intra-operative transfusion rate was higher in the clopidogrel group (22/60, 36.7%) than that in the control group (12/60, 20.0%) (P < 0.050). However, there was no significant difference in the blood transfusion rate during the entire perioperative period (26/60, 43.3% vs. 20/60, 33.3%; clopidogrel group vs. control group, respectively; P > 0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups.
CONCLUSIONS
Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.
Aged
;
Case-Control Studies
;
Clopidogrel/therapeutic use*
;
Hip Fractures/surgery*
;
Humans
;
Platelet Aggregation Inhibitors/adverse effects*
;
Retrospective Studies
;
Ticlopidine/adverse effects*

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