1.The role of polyunsaturated fatty acid lipid peroxidation in ferroptosis after intracerebral hemorrhage: a review of mecha-nisms and therapeutic implications.
Man GUO ; Guohui ZHAO ; Zhibiao CAI ; Zhenyu ZHANG ; Jie ZHOU
Journal of Zhejiang University. Medical sciences 2025;54(5):694-704
Ferroptosis, a regulated cell death process distinct from apoptosis, is characterized by iron dysregulation and reactive oxygen species (ROS) accumulation. After intracerebral hemorrhage (ICH), decreased cerebral blood flow and iron released from erythrocytes trigger lipid peroxidation-particularly of polyunsaturated fatty acids (PUFAs)-through a cascade of reactions in local brain tissues, promoting ferroptosis. Mitochondrial dysfunction and neuroinflammation further elevate ROS, exacerbating lipid peroxidation and accelerating neuronal ferroptosis. Thus, PUFA peroxidation and associated metabolic pathways play a critical role in ICH-related neuronal damage. This review summarizes current understanding of how PUFA peroxidation contributes to ferro-ptosis after ICH, discusses key regulatory mechanisms involving lipid and iron metabolism, and highlights potential therapeutic strategies targeting ferroptosis to improve neurological outcomes.
Ferroptosis/physiology*
;
Humans
;
Cerebral Hemorrhage/pathology*
;
Lipid Peroxidation
;
Fatty Acids, Unsaturated/metabolism*
;
Reactive Oxygen Species/metabolism*
;
Iron/metabolism*
;
Animals
;
Mitochondria/metabolism*
2.IgA vasculitis with necrosis of the small intestine secondary to monoclonal gammopathy of renal significance: A case report.
Yan DING ; Chaoran LI ; Wensheng HUANG ; Linzhong ZHU ; Lifang WANG ; Doudou MA ; Juan ZHANG ; Lianjie SHI
Journal of Peking University(Health Sciences) 2024;56(6):1101-1105
Monoclonal gammopathy of undetermined significance combined with renal damage is named monoclonal gammopathy of renal significance. There are few reports about IgA vasculitis in patients with monoclonal gammopathy of undetermined significance. Here, we report a case of monoclonal gammopathy of renal significance, who had manifestations of IgA vasculitis, including purpura, gastrointestinal bleeding and joint pain. The patient had elevated serum creatinine levels, prompting further investigation through immunofixation electrophoresis and bone marrow aspiration biopsy. Immunofixation electrophoresis showed IgA-λ-type monoclonal immunoglobulin, while the bone marrow aspiration biopsy suggested plasmacytosis. Kidney biopsy indicated membranous hyperplastic glomerulonephritis, light and heavy chain deposition, IgA-λ. The patient was diagnosed with monoclonal gammopathy of renal significance. In light of the elevated serum creatinine, the patient was treated with chemotherapy regimen (bortezomib +cyclophosphamide +dexamethasone). After chemotherapy, there was no significant improvement in the patient's renal function. Subsequently, the patient experienced abdominal pain, skin purpura, joint pain and severe gastrointestinal bleeding. Gastroenteroscopy did not find the exact bleeding position. Angiography revealed hyperplasia of left jejunal artery. Surgical operation found that the bleeding site was located between the jejunum and ileum, where scattered hemorrhagic spots and multiple ulcers were present on the surface of the small intestine, with the deepest ulcers reaching the serosal layer. And the damaged intestine was removed during the operation. Intestinal pathology showed multiple intestinal submucosal arteritis, rusulting in intestinal wall necrosis and multiple ulcers. Considering intestinal lesions as gastrointestinal involvement of IgA vasculitis, methylprednisolone was used continually after the operation, and the patient's condition was improved. However, after half a year, the patient suffered a severe respiratory infection and experienced a recurrence of serious gastrointestinal bleeding. It was considered that the infection triggered the activity of IgA vasculitis, accompanied by gastrointestinal involvement. Finally, the patient died from gastrointestinal bleeding. The present case represented a patient with monoclonal gammopathy of renal significance and IgA vasculitis, prominently presenting with renal insufficiency and severe gastrointestinal bleeding, making the diagnosis and treatment process complex. Patients with IgA monoclonal gammopathy who presented with abdominal pain, purpura, and arthralgia should be vigilant for the possibility of concomitant IgA vasculitis. The treatment of cases with IgA vasculitis combined with monoclonal gammopathy of renal significance was rather challenging. Plasma cell targeting therapy might be an effective regimen for IgA vasculitis with monoclonal gammopathy. However, patients with poor renal response to the treatment indicated poor prognosis.
Humans
;
Cyclophosphamide/administration & dosage*
;
Gastrointestinal Hemorrhage/etiology*
;
IgA Vasculitis/complications*
;
Immunoglobulin A
;
Intestine, Small/pathology*
;
Kidney/pathology*
;
Kidney Diseases/pathology*
;
Monoclonal Gammopathy of Undetermined Significance/complications*
;
Necrosis
;
Paraproteinemias/complications*
;
Vasculitis/etiology*
3.Endolymphatic sac tumor with intralabyrinthine hemorrhage: a case report.
Cheng ZHANG ; Feitian LI ; Guoming ZHANG ; Chunfu DAI
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2023;37(5):386-388
A 27-year-old female patient suffering endolymphatic sac tumor with intralabyrinthine hemorrhage was reported. The patient had hearing loss in the left ear with continuous tinnitus, and MRI showed the soft tissue shadow of endolymphatic sac. Considering that the tumor involved semicircular canal and vestibule,endolymphatic cyst tumor resection was performed by labyrinth route. After surgery, there was no cerebrospinal fluid leakage and facial nerve function was normal. More importantly, enhanced MRI of temporal bone showed no tumor recurrence 1 year after surgery.
Female
;
Humans
;
Adult
;
Endolymphatic Sac/surgery*
;
Neoplasm Recurrence, Local/pathology*
;
Labyrinth Diseases
;
Tinnitus
;
Ear Neoplasms/pathology*
;
Bone Neoplasms
;
Hemorrhage
4.Risk factors for massive hemorrhage after radical nephrectomy and removal of venous tumor thrombus.
Dong LAN ; Zhuo LIU ; Yu Xuan LI ; Guo Liang WANG ; Xiao Jun TIAN ; Lu Lin MA ; Shu Dong ZHANG ; Hong Xian ZHANG
Journal of Peking University(Health Sciences) 2023;55(5):825-832
OBJECTIVE:
To investigate and analyze the risk factors of massive hemorrhage in patients with renal cell carcinoma and venous tumor thrombus undergoing radical nephrectomy and removal of venous tumor thrombus.
METHODS:
From January 2014 to June 2020, 241 patients with renal cancer and tumor thrombus in a single center of urology at Peking University Third Hospital were retrospectively analyzed. All patients underwent radical nephrectomy and removal of venous tumor thrombus. The relevant preoperative indicators, intraoperative conditions, and postoperative data were statistically analyzed by using statistical software of SPSS 18.0. The main end point of the study was intraoperative bleeding volume greater than 2 000 mL. Logistic regression analysis was used to determine the relevant influencing factors. First, single factor Logistic regression was used for preliminary screening of influencing factors, and variables with single factor Logistic regression analysis P < 0.05 were included in multivariate Logistic regression. In all statistical analyses, P < 0.05 is considered statistically significant.
RESULTS:
Among the 241 patients included, there were 60 cases of massive hemorrhage, 48 males and 12 females, with a median age of 62 years. The number of non-massive hemorrhage was 181. There were 136 males and 45 females, with a median age of 59 years. Univariate analysis showed that the clinical symptoms (both systemic and local symptoms, OR 2.794, 95%CI 1.087-7.181, P=0.033), surgical approach (open surgery, OR 9.365, 95%CI 4.447-19.72, P < 0.001), Mayo grade (Mayo 3-4, OR 5.257, 95%CI 2.806-10.886, P < 0.001), American Society of Anesthesiologists (ASA) score (ASA level 3, OR 2.842, 95%CI 1.338-6.036, P=0.007), preoperative hemoglobin (OR 0.978, 95%CI 0.965-0.991, P=0.001), preoperative platelet count (OR 0.996, 95%CI 0.992-1.000, P=0.037), maximum tumor thrombus width (OR 1.061, 95%CI 1.033-1.091, P < 0.001), Complicated with bland thrombus (OR 4.493, 95%CI 2.264-8.915, P < 0.001), adrenalectomy (OR 3.101, 95%CI 1.614-5.958, P=0.001), segmental resection of the inferior vena cava (OR 2.857, 95%CI 1.395-5.852, P=0.004). There was a statistically significant difference in these aspects(P < 0.05). Multivariate Logistic regression analysis showed that there was a statistically significant difference in surgical approach (open surgery, OR 6.730, 95%CI 2.947-15.368;P < 0.001), Mayo grade (Mayo 3-4, OR 2.294, 95%CI 1.064-4.948, P=0.034), Complicated with bland thrombus (OR 3.236, 95%CI 1.492-7.020, P=0.003).
CONCLUSION
Combining the results of univariate and multivariate Logistic regression analysis, the surgical approach, Mayo grade, and tumor thrombus combined with conventional thrombus were associated risk factors for massive hemorrhage during surgery for renal cell carcinoma with tumor thrombus. Patients who undergo open surgery, high Mayo grade, and tumor thrombus combined with conventional thrombus are at a relatively higher risk of massive hemorrhage.
Male
;
Female
;
Humans
;
Middle Aged
;
Carcinoma, Renal Cell/pathology*
;
Retrospective Studies
;
Thrombosis/etiology*
;
Kidney Neoplasms/pathology*
;
Vena Cava, Inferior/surgery*
;
Nephrectomy/methods*
;
Thrombectomy/methods*
;
Risk Factors
;
Hemorrhage
5.Efficacy evaluation of novel oral anticoagulants in patients with cirrhosis accompanied with portal vein thrombosis: a meta-analysis.
Xiao Tong XU ; Yu Wei LIU ; Jing Lan JIN
Chinese Journal of Hepatology 2023;31(6):614-620
Objective: To analyze the safety and efficacy of using novel oral anticoagulants (rivaroxaban and others) in patients with cirrhosis accompanied with portal vein thrombosis (PVT). Methods: Clinical research literature published from the establishment of the database to June 20, 2021, was retrieved from PubMed, Web of Science, CNKI, Wanfang, and Weipu databases by combining subject terms and free words. RevMan software was used for the random group meta-analysis model. Results: In terms of PVT recanalization, the novel oral anticoagulants (such as low molecular weight heparin and others) had a higher recanalization rate than traditional anticoagulants (OR = 13.75, 95%CI 3.58-52.9, P = 0.000 1). In terms of bleeding, the novel oral anticoagulants did not increase the risk of bleeding compared with traditional anticoagulants (OR = 2.42, 95%CI 0.62-9.41, P = 0.20). Conclusion: The novel oral anticoagulant drugs are superior to traditional anticoagulants in terms of the occurrence of PVT recanalization; however, there is no statistically significant difference in terms of the occurrence of bleeding between the two groups.
Humans
;
Portal Vein/pathology*
;
Treatment Outcome
;
Venous Thrombosis/complications*
;
Liver Cirrhosis/pathology*
;
Anticoagulants/therapeutic use*
;
Hemorrhage
6.SpyGlass in Diagnosis of Hepatocellular Carcinoma with Right Hepatic Duct Tumor Thrombus Hemorrhage: A Case Report.
Li-Hua GUO ; Min MIAO ; Guo-Liang YE
Chinese Medical Sciences Journal 2023;38(4):309-314
Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.
Female
;
Humans
;
Middle Aged
;
Carcinoma, Hepatocellular/diagnostic imaging*
;
Jaundice, Obstructive/etiology*
;
Liver Neoplasms/diagnostic imaging*
;
Hepatic Duct, Common/pathology*
;
Thrombosis/complications*
;
Hemorrhage/complications*
7.Effects of MCC950 on nerve injury in rats with intracerebral hemorrhage.
Ya-Jing GUO ; Jing REN ; Han LIU ; Ting-Ting LI ; Shuai ZHANG ; Hong WANG
Chinese Journal of Applied Physiology 2022;38(1):11-16
Objective: To investigate the effects of the pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950 on nerve injury in rats with intracerebral hemorrhage(ICH). Methods: Seventy-two SD rats were randomly divided into three groups (n=24): Sham group, ICH group and MCC950 group. ICH group and MCC950 group rats were injected with autogenous non-anticoagulant blood to establish ICH model, and then the rats in MCC950 group were intraperitoneally injected with MCC950 at the dose of 10 mg/kg(2 mg/ml) for 3 days after ICH model was established. Seventy-two hours after the establishment of the model, the forelimb placement test, the corner test and mNSS score were performed to observe the neurological function of the rats with ICH. The volume of hematoma was observed in fresh brain tissue sections. HE staining was used to observe the pathological changes of brain tissue. The dry-wet weight ratio was calculated to evaluate the changes of brain tissue edema. The degeneration of neurons was observed by FJC staining. The neuronal apoptosis was observed by TUNEL staining. The protein expression and activation levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD were determined by Western blot. Results: Compared with sham group, the percentage of successful placement of left forelimb and left turn was decreased significantly (P<0.01, P<0.05), mNSS score was increased significantly (P<0.01) in ICH group. Hematoma volume was increased significantly, the number of microglial cells around the hematoma was increased, the number of neurons was decreased, nerve cell swelled, some cells showed pyknotic necrosis, and the staining was deepened. The water content of the right base was increased significantly (P<0.05). The number of FJC positive and TUNEL positive cells around the hematoma was increased significantly (P<0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were increased significantly (P<0.01, P< 0.05). Compared with ICH group, the percentage of successful placement of left forelimb and left turn was increased significantly in MCC950 group (P<0.05), while the mNSS score and the volume of hematoma were decreased significantly (P<0.01), the swelling degree of nerve cells around the hematoma was reduced significantly, and the number of pyrotic necrotic cells was decreased. The water content of the right base was decreased significantly (P<0.05), and the number of FJC positive and TUNEL positive cells around the hematoma was decreased significantly (P<0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were decreased significantly (P<0.05). Conclusion: MCC950 can ameliorate nerve injury after ICH by inhibiting NLRP3 inflammasome mediated inflammation and pyroptosis.
Animals
;
Caspase 1/metabolism*
;
Cerebral Hemorrhage/pathology*
;
Furans
;
Hematoma
;
Indenes
;
Inflammasomes/metabolism*
;
Interleukin-18
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
;
Rats
;
Rats, Sprague-Dawley
;
Sulfonamides
;
Water
8.MRI and Transvaginal Ultrasound Findings of Atypical Polypoid Adenomyoma: A Case Report.
Ya TAN ; Xue HU ; Xin SONG ; Wen-Jun ZHANG
Chinese Medical Sciences Journal 2022;37(1):82-86
Atypical polypoid adenomyoma (APA) is an uncommon type of polypoid characterized by fibroid stroma and endometrial glands. It occurs mostly in premenopausal women and rarely in postmenopausal women with irregular vaginal bleeding. In our current case, a 76-year-old woman presented with irregular vaginal bleeding. The final pathological diagnosis of the mass was APA. APA is not easy to diagnose before surgery. On the one hand, there was no obvious particularity in imaging features and clinical features, especially for uncomfortably identifying endometrial cancer. On the other hand, APA has a pedicle, attaching to any part of the uterine cavity, which can cause pseudocoel between the mass with the uterine cavity wall. So, when it comes to getting the pathological tissue in the absence of hysteroscopy, it is easy to access to the pseudocoel and obtain endometrial tissue rather than the pathological tissue of the mass. Therefore, preoperative imaging examination is of great significance diagnosis way of thinking to clinicians for APA. In the meantime, pathological tissue of APA can be obtained by hysteroscopy in visual conditions.
Adenomyoma/pathology*
;
Aged
;
Female
;
Humans
;
Hysteroscopy
;
Magnetic Resonance Imaging
;
Pregnancy
;
Uterine Hemorrhage
;
Uterine Neoplasms/diagnostic imaging*
9.Urodynamic and histological evaluation of cyclophosphamide-induced bladder pain syndrome in SD rats.
Lin ZHU ; Wei Yu ZHANG ; Ke Xin XU
Journal of Peking University(Health Sciences) 2022;54(4):735-740
OBJECTIVE:
To establish a model of bladder pain syndrome in SD rats by cyclophosphamide intraperitoneal injection, to evaluate the effectiveness of the model from the urodynamic and histological levels, to lay a zoological foundation for the clinical study of bladder pain syndrome, and to further guide clinical treatment.
METHODS:
Thirty-two 8-week-old SD rats were randomly divided into 4 groups, including acute test group, acute control group, chronic test group, and chronic control group, with 8 rats in each group. The acute test group received intraperitoneal injection of cyclophosphamide 150 mg/kg immediately after the measurement of urodynamic data on the first day, and urodynamic examination was performed again 2 days later. After that, the rats were sacrificed to obtain bladder tissue. In the chronic test group, after measuring the baseline data of urodynamics on the first day, cyclophosphamide 75 mg/kg was intraperitoneally injected on the first, fourth, and seventh days, and the rats were sacrificed after measuring the urodynamic data again on the eighth day to obtain bladder tissue. The acute control group and the chronic control group were injected with the same amount of normal saline during intraperitoneal injection, and the urodynamic testing time point were consistent with the corresponding test groups. Histopathological changes of the bladder were assessed by HE staining.
RESULTS:
In each acute and chronic group, there were no intragroup differences in baseline urodynamic levels between the test and control groups. The urodynamic maximum bladder volume was significantly reduced in the acute test group after administration(t=-2.961, P < 0.05), histologically, severe interstitial edema, obvious inflammatory cell infiltration, mucosal edema and submucosal hemorrhage, and partial urothelium were absent could be seen, which were consistent with acute cystitis performance. The urodynamic maximum bladder capacity was significantly reduced in the chronic test group after administration (t=-3.886, P < 0.05), and the bladder compliance was lower than that in the control group, but not significant, the histological manifestations were urothelial exfoliation, interstitial edema, submucosal hemorrhage, infiltration of inflammatory cells such as lymphocytes, and dense vascular distribution.
CONCLUSION
In the acute test group, a single intraperitoneal injection of cyclophosphamide could induce acute bladder inflammation in the rats. In the chronic test group, repeated injections of cyclophosphamide could induce histological changes in chronic inflammation of chronic bladder pain syndrome in the rats. But the bladder function was not significantly impaired.
Animals
;
Cyclophosphamide/therapeutic use*
;
Cystitis/pathology*
;
Cystitis, Interstitial/drug therapy*
;
Disease Models, Animal
;
Hemorrhage
;
Rats
;
Rats, Sprague-Dawley
;
Urodynamics
10.Immediate postoperative color Doppler ultrasonography on the diagnosis of hemorrhagic complications of liver biopsy and its directed compression hemostasis.
Guo Quan ZHANG ; Ling Yun ZHANG ; Guo Qing HAN ; Yu Hua ZHU ; Ai Min ZHENG
Chinese Journal of Hepatology 2022;30(3):285-289
Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.
Biopsy
;
Hemorrhage/etiology*
;
Hemostasis/physiology*
;
Humans
;
Liver/pathology*
;
Liver Diseases/pathology*
;
Ultrasonography
;
Ultrasonography, Doppler, Color/adverse effects*

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