Objective To summarize the changes of serum ceruloplasmin levels and urinary copper excretion in Wilson’s disease （WD） after living-related liver transplantation(LRLT) and orthotopic liver transplantation(OLT). Methods From September 2000 to November 2003, 140 cases liver transplantation were performed in our Liver Transplantation Center, LRLT and OLT were carried out in 26 patients with WD, three of them had fulminant hepatic failure and the others had end-stage hepatic insufficiency. All the recipients had low serum ceruloplasmin levels 〔(124.8±22.8) mg/L〕 and high urinary copper excretion 〔(1 524.8±328.6) μg/24h〕 before transplantation. The serum ceruloplasmin levels and urinary copper excretion were within normal limits in 22 donors 〔(230.4±29.6) mg/L〕 and ＜50 μg/24h〕. Results All recipients recovered satisfactorily. After operation 1, 3, 6,12 months, in OLT group, serum ceruloplasmin level and urinary copper excretion were (320.2±36.8) mg/L, (380.4±45.6) mg/L, (360.5±37.6) mg/L, (356.2±27.6) mg/L and (240.4±22.8) μg/24h, (86.5±10.6) μg/24h, (54.2±6.8) μg/24h, (46.8±3.4) μg/24h; While in LRLT group, serum ceruloplasmin levels and urinary copper excretion were (216.8±20.4) mg/L, (248.5±32.6) mg/L, (285.4±44.3) mg/L, (260.2±36.6) mg/L and (380.8±37.6) μg/24h, (150.6±24.5) μg/24h, (75.5±9.6) μg/24h, (60.3±5.8) μg/24h. Conclusion OLT and LRLT are curative procedure in WD manifested as fulminant hepatic failure and/or end-stage hepatic insufficiency. After liver transplantation, the serum ceruloplasmin level can increase to its normal range while urinary copper excretion decreases.
目的 采用RNA干扰技术沉默CCS（copper chaperone for SOD1）基因，构建相关小干扰RNA（siRNA），探索出针对CCS的高效siRNA序列。 方法 合成用于人脐静脉内皮细胞（HUVEC）细胞中沉默CCS基因的siRNA。应用脂质体转染的方法在HUVEC细胞中对CCS基因进行RNA沉默。蛋白免疫印迹Western blotting检测沉默前后CCS蛋白表达变化的情况，甲基四唑蓝法MTT检测转染前后细胞活力。最后用单因素方差分析对数据进行统计学分析，以确定有效的siRNA序列。 结果 转染前后细胞形态无肉眼可见变化，转染后细胞活力分别为98.5%和98.8%。CCS蛋白沉默率分别为63.7%和61.4%。 结论 采用siCCS-2和siCCS-3序列转染条件对HUVEC细胞活力损伤小，CCS沉默效率高，实验条件稳定，重复性好。为我们继续研究沉默CCS后抑制血管内皮细胞的生长增殖、血管形成提供了稳定的实验基础。
ObjectiveTo improve the understanding of clinicians by reports and literature review of patients with rare diseases of Menkes disease.MethodsHigh-throughput sequencing and Sanger sequencing were used to verify the genes of epilepsy, and the mutations were verified in three probands and two parents. The patient's clinical manifestations, EEG, imaging, gene and prognostic characteristics were analyzed.ResultsAll the three patients developed onset in infancy, with hair thinning and curling, and various forms of seizures. Three patients had epileptiform discharges during the EEG interval, and all clinical seizures were recorded. Skull MR showed white matter long T1, long T2 abnormal signal, cerebral artery tortuosity, proband 3 appeared subdural effusion. Three patients had poor efficacy after taking anti-epileptic drugs. The proband one and the proband two did not show significant progress after using histidine copper, but could not alleviate the existing neurological damage.ConclusionMenkes disease occurs frequently in infants, clinical manifestations may be different, some clinical manifestations may be atypical, and currently it is an incurable disease, but the use of histidine copper in the neonatal period can improve survival and reduce nervous system injury. It should be diagnosed early. and the treatment of indications should not be guided by the patient's genotype.
Objective To investigate the relationship between trace elements in synovial fluid and cartilage and severity of knee osteoarthritis (KOA). MethodsPatients with KOA who underwent knee arthrocentesis or total knee arthroplasty (TKA) were recruited based on inclusion criteria between June 2021 and December 2021. Synovial fluid samples were obtained during knee arthrocentesis and TKA, and participants were divided into the mild group (grading Ⅰ/Ⅱ) and the severe group (grading Ⅲ/Ⅳ) according to the Kellgren-Lawrence grading (K-L grading). Cartilage samples with different degrees of wear were collected during the TKA from the same patient and were divided into mild wear (0-1 point) and severe wear (2-4 points) groups based on the Pelletier score. The contents of copper (Cu), zinc (Zn), and manganese (Mn) in synovial fluid and cartilage were evaluated by inductively coupled plasma mass spectrometry, and the differences between groups were compared. ResultsA total of 33 synovial fluid samples were collected, including 19 specimens from 14 patients who underwent knee arthrocentesis of mild group, with 5 bilateral sides knee arthrocentesis in them, and 14 specimens from 14 TKA patients of severe group. The patients were significantly younger in the mild group than in the severe group (P<0.05), but there was no significant difference in gender or body mass index between the two groups (P>0.05). Nineteen pairs of cartilage samples with mild and severe wear were collected from severe KOA patients (K-L grading Ⅲ and Ⅳ), including 9 males and 10 females, with an average age of 70.4 years (range, 58-80 years). The body mass index ranged from 21.2 to 30.7 kg/m2, with an average of 25.6 kg/m2. The content of Zn in synovial fluid and cartilage from KOA patients was the highest, followed by Cu, and Mn was the lowest. The Cu content in synovial fluid was significantly higher in the severe group than in the mild group (P<0.05), and in the severe wear group than in the mild wear group (P<0.05). There was no significant difference in Zn and Mn content between the two groups (P>0.05). Conclusion The Cu content increases with the severity of cartilage wear in patients with KOA.
Objective To summarize the research progress of copper and its derivatives in gastrointestinal tumors in recent years, aiming to provide reference for clinical diagnosis and treatment decisions. Method The literatures related to copper homeostasis and copper death in recent years were read and summarized, and the research progress on the role of copper in cancer and copper applications in cancer diagnosis and treatment was reviewed. Results Copper was an essential trace element involved in a variety of basic biological processes. Elevated levels of copper in serum and tissues were associated with the development of tumors. As the mechanisms of copper action in various gastrointestinal tumors were being investigated, the use of copper and related derivatives in the treatment of cancer patients had become a new strategy. Conclusion Copper and its derivatives have a promising future in the treatment of gastrointestinal tumors, but their benefits in clinical patients still need to be demonstrated in numerous clinical trials.
Amine oxidase copper-containing 1 (AOC1) is a key member of copper amine oxidase family, which is responsible for deamination oxidation of histamine and putrescine. In recent years, AOC1 has been reported to be associated with various cancers, with its expression levels significantly elevated in certain cancer cells, suggesting its potential role in cancer progression. However, its function in lipid metabolism still remains unclear. Through genetic analysis, we have discovered a potential relationship between AOC1 and lipid metabolism. To further investigate, we generated Aoc1−/− mice and characterized their metabolic phenotypes on both chow diet and high-fat diet (HFD) feeding conditions. On HFD feeding conditions, Aoc1−/− mice exhibited significantly higher fat mass and impaired glucose sensitivity, and lipid accumulation in white adipose tissue and liver was also increased. This study uncovers the potential role of AOC1 in lipid metabolism and its implications in metabolic disorders such as obesity and type 2 diabetes, providing new targets and research directions for treating metabolic diseases.