1.Mechanism and Current Situation of Decorporation Agents for Radionuclide Contamination in vivo
Bing-Yan KOU ; Yu-Feng GUO ; Xu-Hong DANG ; Xiao-Ming LIU
Progress in Biochemistry and Biophysics 2024;51(11):2960-2970
Radioactive contamination can occur during nuclear accidents, loss of radioactive sources and the use of radiation for photography, disinfection and detection. When the human body is accidentally contaminated by radionuclides, radionuclides can cause harm to the human body through inhalation, ingestion, direct transdermal absorption and contaminated wounds into body tissues and organs. In the treatment of radionuclide contamination in vivo, the main way is decorporation therapy, which mainly uses specific decorporation agents to selectively bind radionuclides to form stable non-toxic complexes, thereby preventing their deposition in the body, accelerating excretion, and reducing the total accumulation of radionuclides in human tissues. At present, internal radionuclide decorporation agents promote the release of radionuclides from the body mainly by stopping the entry of radionuclides into the body, ion exchange, chelation, and binding of exportants to carriers. But recent studies have found that lysosomal exocytosis, the natural clearing function of activated cells, also has a significant exportation effect. In this paper, we first introduced and analyzed the mechanism and research status of radionuclide decorporation agents that have been used in clinical practice, such as the blocking effect of potassium iodide, the ion exchange effect of Prussian blue, the chelation effect of DTPA, and the urine alkalinization effect of sodium bicarbonate. The second part introduces the mechanism and research status of promising radionuclide decorporation agents. Among them, 3,4,3-LI (1,2-HOPO) and 5-LIO (Me-3,2-HOPO) are the most promising ones and have been approved for phase I clinical trials. Others such as catecholamines, polyethyleneimine and fullerenes are also being studied with great potential. Polyethyleneimine, as a biological macromolecular chelator, has more chelating sites and stronger targeting effects than small molecule chelators, and has achieved a real breakthrough in decorporation. Fullerenes are known as “free radical sponges” with good free radical scavenging ability and antioxidant properties. In recent years, biomaterials have been widely used in the field of radionuclide decorporation, which has greatly improved the decorporation efficiency. Chitosan and pectin have shown great advantages in promoting radionuclide decorporation, chitosan can adsorb metal ions through electrostatic interaction and chelation, and can also react with free radicals to remove free radicals generated after radionuclides enter the body. Pectin can promote uranium efflux, but the exact mechanism remains unclear. Liposomes and nanomaterials as carriers enhance the intracellular drug delivery, prolong the retention time of drugs in the body, reduce adverse reactions, and make the traditional efflux enhancers glow with new vitality and have good development prospects. The last part summarizes and looks forward to the future research direction of radionuclide decorporation agents. At present, the research on decorporation agents at home and abroad is mostly stuck in the stage of drug development and drug synthesis, and few have actually entered the clinical trial stage. Therefore, the optimization of existing decorporation agents and the development of new ligands are critical. The targeting, biological safety, oral availability, and treatment needs of large-scale contamination scenarios are still the focus of attention. In addition, from the point of view of the mechanism itself, it is a new idea to promote the emission of radionuclides by activating potential channels, which can be continuously explored.
3.Cardiometabolic disease patterns among elderly patients with colorectal cancer in China.
Wang Ping JIA ; Fu Yin KOU ; Hong Li XU ; Ke HAN ; Wen Zhe CAO ; Sheng Shu WANG ; Yang SONG ; Shan Shan YANG ; Ya Feng YAN ; Feng CAO ; Wan Guo XUE ; Ya Bin WANG ; Wen Wen MENG ; Miao LIU ; Yao HE
Chinese Journal of Oncology 2022;44(2):173-177
Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.
Aged
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Aged, 80 and over
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Cardiovascular Diseases
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China/epidemiology*
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Colorectal Neoplasms
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Female
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Humans
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Male
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Retrospective Studies
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Risk Factors
4.Effect of Combined Therapy of Lung and Intestine on NF-κB Inflammatory Pathway and Macrophage Polarization in LPS-induced Acute Lung Injury Rats
Rui-zhe WANG ; Yu-le KOU ; Hong-wei HE ; Yi HUI ; Shu-guang YAN ; Jing-tao LI ; Jie SHI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):93-100
ObjectiveTo investigate the effect of combined therapy of lung and intestine (Mahuangtang + Da Chengqitang) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and its protective mechanism. MethodWistar rats were randomly divided into blank group, model group, low-, medium-, and high-dose groups with combined therapy of lung and intestine , and dexamethasone group. LPS (10 mg·kg-1) was given (ip) to induce ALI in rats. The general state of rats in each group was observed and recorded. The body temperature of rats in each group was recorded 0-8 h after modeling by means of anal temperature measurement. Serum and lung tissues were collected 24 h after modeling. Serum levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and arginase-1 (Arg-1) were determined by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein levels of nuclear factor kappa B p65 (NF-κB p65), phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB inhibitor α (IκBα), and phosphorylated IκBα (p-IκBα) in lung tissues of rats. The levels of classically activated (M1) macrophage marker CD80 and IL-1β and macrophage markers F4/80 and IL-10 were detected by double immunofluorescence. ResultCompared with the blank group, the model group showed increased body temperature and thermal response index (TRI), elevated serum levels of pro-inflammatory factor TNF-α and IL-1β and anti-inflammatory factor IL-10 (P<0.01), up-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues (P<0.01), and increased levels of F4/80, CD80, and IL-1β in lung tissues (P<0.01). Compared with the model group, the lung-intestine combined treatment groups and the dexamethasone group exhibited decreased body temperature and TRI in rats (P<0.01), declined serum levels of inflammatory factor TNF-α and IL-1β (P<0.05, P<0.01), elevated serum levels of anti-inflammatory factor IL-10 and Arg-1 (P<0.05, P<0.01), down-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues (P<0.05, P<0.01), decreased levels of CD80 and IL-1β, and increased levels of IL-10 in lung tissues (P<0.01), while the level of F4/80 was not significantly changed. ConclusionThe combined therapy of lung and intestine can obviously alleviate the fever and inflammatory state of ALI rats, and the mechanism may be related to the inhibition of NF-κB inflammatory pathway and the polarization of lung tissue macrophages to anti-inflammatory phenotype.
5.Thoughts and suggestions on co-administration of seasonal influenza vaccine and COVID-19 vaccine.
Zeng Qiang KOU ; Li Jun LIU ; Chang Sha XU ; Hong Ting ZHAO ; Zhao Nan ZHANG ; Xiao Kun YANG ; Zhi Bin PENG ; Lu Zhao FENG ; Ai Qiang XU ; Da Yan WANG ; Zhi Ping CHEN ; Jian Dong ZHENG ; Zi Jian FENG ; Wen Zhou YU
Chinese Journal of Preventive Medicine 2022;56(10):1395-1400
In the context of the global pandemic of COVID-19, the epidemic intensity, epidemic characteristics and infection risk of influenza have presented new features. COVID-19 and influenza have simultaneously emerged in many regions of the world. COVID-19 and influenza are similar in terms of transmission mode, clinical symptoms and other aspects. There are also similarities in the mechanism of influenza virus and novel coronavirus on cells. At the same time, it is feasible and significant to do a good job in the prevention and control of COVID-19 and influenza. This paper discusses the relevant strategies and measures for the joint prevention and control of influenza and novel coronavirus from the aspects of influenza vaccination to prevent co-infection, simultaneous vaccination of influenza vaccine and novel coronavirus vaccine, etc., and puts forward corresponding thoughts and suggestions, in order to provide scientific support for the formulation of strategies on seasonal influenza vaccine and novel coronavirus vaccination.
Humans
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Influenza Vaccines
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Influenza, Human/epidemiology*
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COVID-19 Vaccines
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COVID-19/prevention & control*
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Seasons
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Vaccination
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SARS-CoV-2
6.Adherence to adjuvant with therapy imatinib in patients with gastrointestinal stromal tumor: a national multi-center cross-sectional study.
Peng ZHANG ; Jun ZHANG ; Bo ZHANG ; Wen Chang YANG ; Jun Bo HU ; Xiao Feng SUN ; Gang ZHAI ; Hao Ran QIAN ; Yong LI ; Hao XU ; Fan FENG ; Xing Ye WU ; He Li LIU ; Hong Jun LIU ; Hai Bo QIU ; Xiao Jun WU ; Yan Bing ZHOU ; Kun Tang SHEN ; You Wei KOU ; Yang FU ; Zhi Gang JIE ; Xiao Ming ZOU ; Hui CAO ; Zhi Dong GAO ; Kai Xiong TAO
Chinese Journal of Gastrointestinal Surgery 2021;24(9):775-782
Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
Aged
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Aged, 80 and over
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Antineoplastic Agents/therapeutic use*
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Chemotherapy, Adjuvant
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Cross-Sectional Studies
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Female
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Gastrointestinal Stromal Tumors/drug therapy*
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Humans
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Imatinib Mesylate/therapeutic use*
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Male
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Middle Aged
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Neoplasm Recurrence, Local/drug therapy*
7. Projections from Infralimbic Cortex to Paraventricular Thalamus Mediate Fear Extinction Retrieval
Yan TAO ; Cheng-Yun CAI ; Jia-Yun XIAN ; Xiao-Lin KOU ; Yu-Hui LIN ; Cheng QIN ; Hai-Yin WU ; Lei CHANG ; Chun-Xia LUO ; Dong-Ya ZHU ; Dong-Ya ZHU ; Dong-Ya ZHU
Neuroscience Bulletin 2021;37(2):229-241
The paraventricular nucleus of the thalamus (PVT), which serves as a hub, receives dense projections from the medial prefrontal cortex (mPFC) and projects to the lateral division of central amygdala (CeL). The infralimbic (IL) cortex plays a crucial role in encoding and recalling fear extinction memory. Here, we found that neurons in the PVT and IL were strongly activated during fear extinction retrieval. Silencing PVT neurons inhibited extinction retrieval at recent time point (24 h after extinction), while activating them promoted extinction retrieval at remote time point (7 d after extinction), suggesting a critical role of the PVT in extinction retrieval. In the mPFC-PVT circuit, projections from IL rather than prelimbic cortex to the PVT were dominant, and disrupting the IL-PVT projection suppressed extinction retrieval. Moreover, the axons of PVT neurons preferentially projected to the CeL. Silencing the PVT-CeL circuit also suppressed extinction retrieval. Together, our findings reveal a new neural circuit for fear extinction retrieval outside the classical IL-amygdala circuit.
8.Expression Level and Target Gene Prediction of miR-181b in Patients with Chronic Lymphocytic Leukemia.
Zhen KOU ; Hong LIU ; Yi-Chun WANG ; Qin HUANG ; Zeng-Sheng WANG ; Zai-Li Nu Er GU ; Tao LANG ; Yu-Ling NIE ; Li AN ; Zi-Gu Li A ; He-Ta Bai Er MU ; Xiao-Yan ZHANG ; Ling FU ; He-Mai Jiang AI ; Min MAO ; Xiao-Min WANG ; Yan LI
Journal of Experimental Hematology 2020;28(3):808-814
OBJECTIVE:
To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics.
METHODS:
Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes.
RESULTS:
The expression level of miR-181b in CLL patients was significantly lower than that in control group (P<0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P<0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P<0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging.
CONCLUSION
The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins
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Cell Proliferation
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Humans
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Leukemia, Lymphocytic, Chronic, B-Cell
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genetics
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MicroRNAs
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Prognosis
9.Technical improvement in retroperitoneal laparoscopic living donor nephrectomy: report of 193 cases
Lei ZHAO ; lin Lu MA ; xian Hong ZHANG ; fei Xiao HOU ; Lei LIU ; Yan FU ; geng Yun KOU ; meng Yi SONG
Journal of Peking University(Health Sciences) 2017;49(5):867-871
Objective:To summarize our experience of retroperitoneal laparoscopic living donor nephrectomy,our continuous technical improvements and refinement of this skill and standardization of each procedure of this operation.Methods:Having approved by hospital ethical committee and local government administration,a total of 193 living donors underwent retroperitoneal laparoscopic living donor nephrectomy from Dec.2003 to Feb.2016 in our department.Under general anaesthesia,the operation was performed through 3 lumbar ports.After the kidney was liberated fully and the ureter was severed 7-8 cm under the lower pole of the kidney,the renal artery and vein were blocked with endo-cut or hem-o-lok separately and then severed.Then the kidney was taken out quickly and flushed with 4 ℃ kidney preserving fluid immediately,the donor kidneys were then preserved in iced saline until kidney transplantation.Clinical data about operation time,volume of blood loss,perioperative complications,renal function of both donors and recipients before and after operation were collected.Results:The 193 retroperitoneal laparoscopic living donor nephrectomy operations were successful with only one operation was converted to open living donor nephrectomy because of hemorrhage and unclear operation field during the operation.The average operation time was 85 min (55-135 min),the average blood loss was 60 mL (20-200 mL),and no donor needed blood transfusion during or after operation.Three donors were found to have hematoma of renal fossa after operation and none of them required further treatment.The average hospital stay after operation was 5.7 days (4-9 days).In the study,162 donors were followed up for an average of 42 months (1-58 months) and they were all healthy.Two kidney recipients had urinary bladder anastomosis leakage after operation and both needed surgical repair,a new anastomosis of ureter and bladder were made.Three kidney recipients had kidney subcapsular hematoma but required no further treatment.One kidney recipient had delayed graft function and recovered finally and the renal function of other recipients were all normal.Renal function of both donors and recipients during the follow up period were normal.Conclusion:Retroperitoneal laparoscopic living donor nephrectomy is a safe and reliable technique,it may become a standardized operation for living kidney transplantation after continuous technical improvement.Precautions must be taken to avoid complications and a skilled hand is necessary for success.
10.Clinical application of modified electroconvulsive therapy in psychiatric inpatients
Qian WANG ; Yan LI ; yun Yun LI ; na Yan KOU ; san Hai ZHANG ; xing Hong ZHANG
Journal of Xinxiang Medical College 2017;34(11):978-981
Objective To investigate the clinical application of modified electroconvulsive therapy (MECT),and provide the references for more standardized and rational use of MECT.Methods A retrospective study was performed by stratified random sampling method.The clinical data of 1 330 psychiatric inpatients from January 2006 to December 2015 in Henan Psychiatric Hospital were analyzed retrospectively,and the clinical application of MECT was investigated,including the proportion of psychiatric inpatients receiving MECT,the situation of combined use of MECT and antipsychotic drugs,and the routine examination results before and after MECT.Results The proportion of receiving MECT in schizophrenic patients was the highest,it is 11.36% (81/713),the second was depressive episode (5.61%,12/214),followed by dissociative conversion disorder (5.56%,2/36),bipolar disorder (5.34%,7/131),organic mental disorder (3.23 %,1/31) and other mental disorders (2.93%,6/205).There were significant differences in the distribution of various mental disorders between the non electroshock group and the electroshock group (x2 =21.728,P < 0.05).The proportion of the patients without electric shock and the patients with single drug,two drugs,triple therapy or quadruple therapy was 0.92%,17.43 %,56.88%,21.10% and 3.67%,respectively.The proportion of the patients with two or more antipsychotic drugs was 81.65% in the electroshock group.The antipsychotics were olanzapine (28.44%),clozapine (27.52%),quetiapine (26.61%) and risperidone (24.77 %) according to the drugs used frequently in the electroshock group.The results of routine blood test were compared among the time points of before treatment,the 1st,2nd,3 rd week of MECT and 1 week after MECT in the shock group,which showed that there was significant difference in white blood cell count (F =2.570,P < 0.05);but there was no significant difference in the levels of platelet,hemoglobin and red blood cell (P > 0.05);the level of white blood cell returned to normal within two weeks in 93.33% patients with increased white blood count.The myocardial enzymes and liver function tests were not perfect during the treatment of MECT and after treatment.There was no long-term systematic evaluation of cognitive function and quality of life in patients with electroconvulsive shock.Conclusions The probability of using MECT in the patients with schizophrenia is more than that in the patients with depression.MECT is used in combination with two or more antipsychotic drugs.MECT may cause a short increase in white blood cells,but the white blood cell level in most patients can recover to normal levels after symptomatic treatment.The clinical data for treatment and prognosis in patients with MECT are inadequate,so it is necessary to improve the medical record.

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