1.A study of the dynamic evolution of macrophage infiltration behavior after acute carotid artery thrombosis
Shikai LI ; Jia LIANG ; Yanyan HE ; Qianhao DING ; Chenqing LI ; Yang LIU ; Yingpu FENG ; Wenli ZHAO ; Yumeng HUANG ; Lina SUO ; Tianxiao LI ; Yingkun HE
Chinese Journal of Cerebrovascular Diseases 2024;21(7):433-443
Objective To explore the changes in macrophage infiltration behavior during the dynamic evolution of thrombi following the formation of acute carotid artery thrombosis occlusion(ACTO).Methods 15 healthy male New Zealand rabbits were selected to establish an ACTO model by causing injury to the rabbit carotid artery using surgical sutures treated with ferric chloride.All rabbits were randomly divided into 5 groups according to the end-point time using the random number table method,namely 24-hour group,1 week group,4week group,8 week group,and 12week group postoperatively,with 3 rabbits in each group.At 24 hours post-operation,the ACTO model was examined by DS A.At 24 hours,1 week,4 weeks,8 weeks,and 12 weeks post-operation,samples were taken from the thrombotic arterial segment of the 3 rabbits in each group and embedded in paraffin.The thrombus samples were stained with hematoxylin-eosin(HE)and Martius scarlet blue(MSB)to analyze changes in thrombus morphology and composition(including red blood cells,fibrin and collagen fibers).Orbit Imaging Analysis software was used for semi-quantitative analysis of the thrombus composition components.Using immunohistochemistry to detect the distribution of MO and M2 macrophages in thrombi,aimed to summarize the dynamic evolution of thrombus morphology,composition,and macrophage infiltration behavior at different stages following ACTO occurrence.Results The 24-hour DSA results indicated that all experimental rabbits successfully established the ACTO model.(1)HE staining showed a continuous increase in thrombus size from 24 hours to 1 week.By 4 weeks,signs of thrombus dissolution appeared,and at 8 weeks,neovascularization was observed within the thrombus.By 12 weeks,signs of fibrosis were evident in the thrombus.(2)MSB staining revealed that during the acute phase of thrombus formation(within 24 hours after surgery),red blood cells were the predominant component initially,but after this period,fibrin and collagen fibers became the main components.(3)The detection results of MO macrophages showed that 24 hours after surgery,MO macrophages in the thrombus were not evenly distributed throughout the thrombus,but mainly gathered at the thrombus edge;at 1 week after surgery,the positive area percentage of MO macrophage in the thrombus increased compared with 24 hours after surgery(thrombus edge:[41.7±27.0]%vs.[24.6±16.7]%,thrombus core:[35.7±19.6]%vs.[11.1±10.4]%,all P<0.001),and evenly distributed within the thrombus;at 4 weeks after surgery,MO macrophages in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.7±6.1]%vs.[41.7±27.0]%,thrombus core:[12.1±8.5]%vs.[35.7±19.6]%,all P<0.001),the differences were statistically significant.At 4,8,and 12 weeks after surgery,MO macrophages within the thrombus did not change significantly with time(thrombus edge:[10.7±6.1]%,[8.0±7.7]%,and[8.9±5.3]%;thrombus core:[12.1±8.5]%,[9.5±4.2]%,and[15.7±11.0]%),and the differences were not statistically significant(all P>0.05).In addition,at 12 weeks after surgery,MO macrophages at the thrombus edge was less than the thrombus core([8.9+5.3]%vs.[15.7±11.0]%,P<0.01).The detection results of M2 macrophages showed that 24 hours after surgery,M2 macrophages in the thrombus were widely distributed throughout the thrombus;at 1 week after surgery,the positive area percentage of M2 macrophages in the thrombus increased compared with 24 hours after surgery(thrombus edge:[22.1±11.3]%vs.[11.4±8.7]%,P<0.001;thrombus core:[24.5±9.8]%vs.[7.6±6.0]%,P<0.001);at 4 weeks after surgery,M2 macrophage in the thrombus decreased compared with 1 week after surgery(thrombosis edge:[10.6±3.7]%vs.[22.1±11.3]%,P<0.001;thrombus core:[9.2±4.3]%vs.[24.5±9.8]%,P<0.001);at 8 weeks after surgery,M2 macrophages in the thrombus increased compared with 4 weeks after surgery([17.9±8.8]%vs.[9.2±4.3]%,P<0.001),and the differences were statistically significant.However,M2 macrophages in the thrombus did not change significantly from 8 weeks to 12 weeks after surgery(thrombus edge:[9.4±6.3]%vs.[8.5±5.3]%,P>0.05;thrombus core:[17.9±8.8]%vs.[14.4±10.0]%,P>0.05).In addition,at 8 and 12 weeks after surgery,M2 macrophages in the thrombus core was greater than the thrombus edge(8 weeks after surgery:[17.9±8.8]%vs.[9.4±6.3]%,P<0.001;12weeks after surgery:[14.4±10.0]%vs.[8.5±5.3]%,P<0.001).Conclusions This study successfully established an ACTO animal model and demonstrated for the first time the dynamic evolution of macrophages within 12 weeks post-thrombus formation.Macrophages may played a significant role in both thrombus formation and fibrinolysis,as well as in the promotion of thrombus dissolution and the formation of new blood vessels within the thrombus which may potentially promote the spontaneous reperfusion of the occluded vessels.The results of this study need further verification.
2.Experience summary of coagulation rebalancing therapy for heat stroke-induced coagulopathy
Qingwei LIN ; Xingping DENG ; Huiqiang LIU ; Shikai YU ; Jingchun SONG
Chinese Journal of Hematology 2024;45(S1):97-99
This case report describes the treatment process of a severe exertional heat stroke-induced coagulopathy in a 20-year-old firefighter. Through a comprehensive treatment strategy of five early and one prevention, including early cooling, early anticoagulation, early coagulation factor supplementation, early anti-inflammation, early blood purification, and prevention of complications, the patient was successfully treated. For the management of heat stroke-induced coagulopathy, based on the coagulation rebalancing strategy-namely anticoagulation combined with goal-directed replacement therapy, along with plasma diafiltration (PDF) treatment-the patient's coagulation function was effectively improved without any bleeding or thrombotic events. The patient's coagulation function returned to normal by day 4 of hospitalization, the tracheal tube was removed on day 6, transferred to the general ward after 11 days, and was discharged after 21 days of rehabilitation.
3.Experience summary of coagulation rebalancing therapy for heat stroke-induced coagulopathy
Qingwei LIN ; Xingping DENG ; Huiqiang LIU ; Shikai YU ; Jingchun SONG
Chinese Journal of Hematology 2024;45(S1):97-99
This case report describes the treatment process of a severe exertional heat stroke-induced coagulopathy in a 20-year-old firefighter. Through a comprehensive treatment strategy of five early and one prevention, including early cooling, early anticoagulation, early coagulation factor supplementation, early anti-inflammation, early blood purification, and prevention of complications, the patient was successfully treated. For the management of heat stroke-induced coagulopathy, based on the coagulation rebalancing strategy-namely anticoagulation combined with goal-directed replacement therapy, along with plasma diafiltration (PDF) treatment-the patient's coagulation function was effectively improved without any bleeding or thrombotic events. The patient's coagulation function returned to normal by day 4 of hospitalization, the tracheal tube was removed on day 6, transferred to the general ward after 11 days, and was discharged after 21 days of rehabilitation.
4.Feasibility of interim multipoint core needle biopsy pathological evaluation to predict effect of neoadjuvant therapy for breast cancer (with video)
Shikai HONG ; Shuhan WANG ; Zhengzhi ZHU ; Jianjun LIU ; Kuojun REN ; Shengying WANG
Chinese Journal of Endocrine Surgery 2023;17(5):524-529
Objective:To investigate the feasibility of multipoint core needle biopsy (CNB) at mid-stage to predict the treatment effect of neoadjuvant systemic therapy for breast cancer.Methods:A total of 67 breast cancer cases with indications of neoadjuvant systemic therapy were selected from Mar. 2021 to Nov. 2022.In the fourth cycle of neoadjuvant systemic therapy, core needle biopsy was performed at 3, 6, 9, 12 points of tumor bed and residual tumor foci of breast respectively.The results of CNB were compared with the results of routine pathology of surgery after the completion of neoadjuvant therapy. Matched biopsy and surgical specimens were compared to assess pCR. The accuracy and false negative rate (FNR) of interim pathological assessment were analyzed. The coincidence probability of interim biopsy pathology and pathology of standard surgical excision was verified.Results:The median age of enrolled patients was 49.2 years (21-69 years) .Median maximum tumor diameter before neoadjuvant systemic therapy and residual tumor diameter after neoadjuvant therapy were 40.4 mm (range 21-93mm) and 19.6 mm (range 0-41mm) respectively. A total of 28 patients achieved pCR, and the PCR rates of hormone receptor-positive and HER2-nagative,triple-negative,hormone receptor negative and HER2-positive and hormone receptor-positive and HER2-positive disease were 4/24 (16.7%) ,6/14 (42.9%) ,11/18 (61.1%) ,7/11 (63.6%), respectively. Two cases had no preoperative imaging abnormalities. The results of core needle biopsy pathology of residual tumor lesions in 55 patients were consistent with those of routine post-operation pathology.The results of core needle biopsy pathology of tumor bed of 56 patients was consistent with the routine pathology of surgery. The false negative rate of interim multipoint biopsy pathology of residual tumor foci was 17.9% (12/67). The false negative rate of tumor bed with core needle biopsy was 5.9% (4/67) .Conclusions:CNB guided under ultrasound is feasible in predicting tumor retreat situation in the tumor bed area and residual tumor foci at mid-stage of neoadjuvant therapy. Increasing the number of core needles and improving biopsy techniques may improve the accuracy of pathological evaluation of interim multipoint biopsy.
5.Myelodysplastic syndrome associated with olaparib
Adverse Drug Reactions Journal 2023;25(11):702-704
A 58-year-old female patient underwent ovarian cancer tumor cell reduction surgery for advanced ovarian serous carcinoma in stage ⅣB for more than 3 years and received chemotherapy with paclitaxel and carboplatin regimen for a total of 6 cycles and chemotherapy with doxorubicin liposome and carboplatin regimen for a total of 6 cycles successively. After that, olaparib 300 mg was administered twice daily orally for maintenance treatment. Twenty-five days later, due to the occurrence of grade Ⅱ bone marrow suppression in the patient, the dose of olaparib was reduced to 150 mg in the morning and 300 mg in the evening. After 13 months of olaparib treatment, the patient developed pancytopenia, with the lowest platelet count of 2×10 9/L. Olaparib was stopped immediately.The symptomatic and supportive treatments such as infusion of suspended red blood cells and fresh platelets, elevation of white blood cells,iron replenishment, and platelet elevation were given, but the efficacy was not obvious. Bone marrow flow cytometry detection suggested a high possibility of myelodysplastic syndrome. After discontinuing olaparib for 47 days, the patient died of circulatory failure due to massive abdominal and pelvic bleeding and hemorrhagic shock.
6.Myelodysplastic syndrome associated with olaparib
Adverse Drug Reactions Journal 2023;25(11):702-704
A 58-year-old female patient underwent ovarian cancer tumor cell reduction surgery for advanced ovarian serous carcinoma in stage ⅣB for more than 3 years and received chemotherapy with paclitaxel and carboplatin regimen for a total of 6 cycles and chemotherapy with doxorubicin liposome and carboplatin regimen for a total of 6 cycles successively. After that, olaparib 300 mg was administered twice daily orally for maintenance treatment. Twenty-five days later, due to the occurrence of grade Ⅱ bone marrow suppression in the patient, the dose of olaparib was reduced to 150 mg in the morning and 300 mg in the evening. After 13 months of olaparib treatment, the patient developed pancytopenia, with the lowest platelet count of 2×10 9/L. Olaparib was stopped immediately.The symptomatic and supportive treatments such as infusion of suspended red blood cells and fresh platelets, elevation of white blood cells,iron replenishment, and platelet elevation were given, but the efficacy was not obvious. Bone marrow flow cytometry detection suggested a high possibility of myelodysplastic syndrome. After discontinuing olaparib for 47 days, the patient died of circulatory failure due to massive abdominal and pelvic bleeding and hemorrhagic shock.
7.Clinical characteristics and prognosis of 44 cases of infantile neuroblastoma
Jia HE ; Ying LIU ; Kang HUANG ; Dajun FU ; Shikai CHENG
Chinese Journal of Primary Medicine and Pharmacy 2022;29(4):490-494
Objective:To investigate the clinical characteristics of infantile neuroblastoma (NB) and the factors that affect prognosis.Methods:We retrospectively analyzed the clinical data collected from 44 cases of NB who received treatment in The Fourth Affiliated Hospital of China Medical University from March 2008 to March 2017 to summarize the clinical characteristics of NB and the factors that affect prognosis.Results:Among the 44 cases, 21 were male and 23 were female, with a median age of 5.5 months (range, 0 days-12 months). Four cases had stage I NB, seven cases stage II NB, five cases stage III NB, 15 cases stage IV NB, and 13 cases stage IVs NB. The tumors were located in the adrenal glands and retroperitoneum ( n = 26, 59.1%), posterior mediastinum ( n = 15, 34.1%), pelvis ( n = 2, 4.5%), and neck ( n = 1, 2.3%). The median follow-up time was 90 months (range, 2-144 months). The 3-year and 5-year overall survival rates were 93.2% and 90.9%, respectively. Among 35 cases who survived more than 5 years, 30 cases survived healthily, 5 cases survived with tumor, and 4 cases died. Bone marrow metastasis, bone metastasis, and the extent of tumor resection greatly affect the prognosis of NB ( χ2 = 6.92, 12.19, 4.70, all P < 0.05). Conclusion:The overall prognosis of NB is good in infants. NB mainly occurs in the abdomen. The survival rate of infants with stage IVs NB is lower than that of infants with stages I, II, and III NB. The prognosis of NB occurring in the abdomen is poorer than that occurring in other regions. Bone marrow metastasis, bone metastasis, and the extent of tumor resection are adverse factors affecting the prognosis.
8.Death due to interstitial pneumonia associated with bleomycin
Bingli QI ; Yanli MA ; Shikai LIU
Adverse Drug Reactions Journal 2022;24(12):670-672
A 51-year-old patient with yolk sac tumor received BEP regimen [intramuscular injection of bleomycin 30 mg, on day 2, 9, and 16), IV infusions of etoposide 100 mg/(m 2· d) and cisplatin 20 mg/m 2 on day 1 to 5] after comprehensive staging surgery for ovarian cancer, 21 days was a cycle. No interstitial changes in her lungs were found on chest CT before operation and before each chemotherapy cycle. On the 12th day of the 4th treatment cycle, the patient developed cough, expectoration. Laboratory tests showed white blood cell count 0.63×10 9/L, neutrophil count 0.16×10 9/L, hemoglobin 82 g/L, platelet count 42×10 9/L. Chest CT showed a little grid shadow in both lungs. The patient was diagnosed with myelosuppression (grade Ⅳ) and pulmonary infection. Bleomycin treatment in the 3rd week of the 4th cycle was stopped. Granulocyte colony stimulating factor, thrombopoietin, meropenem, bromhexine, blood transfusion, fluid infusion, and other symptomatic and supportive treatment were given. Bone marrow suppression was relieved, but cough and expectoration were aggravated. Chest CT showed a little grid shadow in both lungs. Glucocorticoid and amphotericin B were added, and non-invasive ventilator assisted ventilation and other symptomatic support treatments were given, but the patient′s condition worsened, and respiratory failure and death occurred 45 days after the 4th cycle of chemotherapy.
9.Death due to interstitial pneumonia associated with bleomycin
Bingli QI ; Yanli MA ; Shikai LIU
Adverse Drug Reactions Journal 2022;24(12):670-672
A 51-year-old patient with yolk sac tumor received BEP regimen [intramuscular injection of bleomycin 30 mg, on day 2, 9, and 16), IV infusions of etoposide 100 mg/(m 2· d) and cisplatin 20 mg/m 2 on day 1 to 5] after comprehensive staging surgery for ovarian cancer, 21 days was a cycle. No interstitial changes in her lungs were found on chest CT before operation and before each chemotherapy cycle. On the 12th day of the 4th treatment cycle, the patient developed cough, expectoration. Laboratory tests showed white blood cell count 0.63×10 9/L, neutrophil count 0.16×10 9/L, hemoglobin 82 g/L, platelet count 42×10 9/L. Chest CT showed a little grid shadow in both lungs. The patient was diagnosed with myelosuppression (grade Ⅳ) and pulmonary infection. Bleomycin treatment in the 3rd week of the 4th cycle was stopped. Granulocyte colony stimulating factor, thrombopoietin, meropenem, bromhexine, blood transfusion, fluid infusion, and other symptomatic and supportive treatment were given. Bone marrow suppression was relieved, but cough and expectoration were aggravated. Chest CT showed a little grid shadow in both lungs. Glucocorticoid and amphotericin B were added, and non-invasive ventilator assisted ventilation and other symptomatic support treatments were given, but the patient′s condition worsened, and respiratory failure and death occurred 45 days after the 4th cycle of chemotherapy.
10.Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy
Xuran ZHAO ; Liang XUAN ; Jun YIN ; Yu TANG ; Huiru SUN ; Shikai WU ; Hao JING ; Hui FANG ; Yongwen SONG ; Jing JIN ; Yueping LIU ; Hua REN ; Bo CHEN ; Shunan QI ; Ning LI ; Yuan TANG ; Ningning LU ; Yong YANG ; Yexiong LI ; Bing SUN ; Shulian WANG
Chinese Journal of Oncology 2021;43(11):1203-1208
Objective:To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment.Methods:A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained.Results:Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval ( HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment ( HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status ( HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval ( HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment ( HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence ( HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status ( HR=1.69, 95% CI: 1.02-2.81), the recurrence interval ( HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence ( HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions:Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

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