Objective: To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Methods: Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3–28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6–95.3) and the DCR was 95.8% (95% CI=78.9–99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4–34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Conclusion Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative firstline treatment option for patients with R/M CC.

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.

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.

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.

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.

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.

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.

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.

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.

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.