1.Radiation environment monitoring and radiation safety management suggestions for typical zircon-titanium ore processing enterprises in Guangxi Province, China
Chen LIN ; Mingfa XU ; Ying ZHANG ; Lun CUI ; Wenbin PENG ; Yichao WU
Chinese Journal of Radiological Health 2025;34(2):283-292
Objective To provide technical support for the formulation of scientific and reasonable supervision measures for enterprises engaged in the exploitation and utilization of ores with associated radionuclides in Guangxi Province, China. Methods A radionuclide analysis was performed on solid materials generated during production processes such as zirconium-titanium ore dressing and processing in multiple enterprises in Guangxi Province. The radiation levels of effluents was measured. Measurement and analysis were performed on the environmental air radon concentration levels and environmental γ-radiation dose rates at the factory boundaries of these enterprises and the surrounding environmental protection targets. Results The air absorption dose rate of γ radiation, the concentrations of radon and its daughters, and the radiation levels of surface water and aerosols at the factory boundaries and in the surrounding environment were all at normal levels. The specific activities of nuclides 238U, 232Th, and 226Ra in the raw ore, zirconium products, rutile products, and monazite products within the factory area were relatively high. The γ radiation air absorption dose rates in the corresponding workshops were also relatively high, with the zirconium-rutile workshop being the area with the highest values. Materials such as zirconium products, rutile, and monazite all showed a certain amount of radon exhalation. Conclusion The radiation level of tailings met the criteria of monitoring exemption, and the enterprises did not generate radioactive solid waste. Attention should be paid to the personal dose of the staff in areas with high radiation dose rates.
2.Gut microbiota and Parkinson's disease.
Lin WANG ; Ying CUI ; Bingyu HAN ; Yitong DU ; Kenish Sirajbhai SALEWALA ; Shiya WANG ; Wenlu ZHAO ; Hongxin ZHANG ; Sichen WANG ; Xinran XU ; Jianpeng MA ; Yan ZHU ; Houzhen TUO
Chinese Medical Journal 2025;138(3):289-297
Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.
Humans
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Parkinson Disease/microbiology*
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Gastrointestinal Microbiome/physiology*
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Dysbiosis/microbiology*
3.Associations between statins and all-cause mortality and cardiovascular events among peritoneal dialysis patients: A multi-center large-scale cohort study.
Shuang GAO ; Lei NAN ; Xinqiu LI ; Shaomei LI ; Huaying PEI ; Jinghong ZHAO ; Ying ZHANG ; Zibo XIONG ; Yumei LIAO ; Ying LI ; Qiongzhen LIN ; Wenbo HU ; Yulin LI ; Liping DUAN ; Zhaoxia ZHENG ; Gang FU ; Shanshan GUO ; Beiru ZHANG ; Rui YU ; Fuyun SUN ; Xiaoying MA ; Li HAO ; Guiling LIU ; Zhanzheng ZHAO ; Jing XIAO ; Yulan SHEN ; Yong ZHANG ; Xuanyi DU ; Tianrong JI ; Yingli YUE ; Shanshan CHEN ; Zhigang MA ; Yingping LI ; Li ZUO ; Huiping ZHAO ; Xianchao ZHANG ; Xuejian WANG ; Yirong LIU ; Xinying GAO ; Xiaoli CHEN ; Hongyi LI ; Shutong DU ; Cui ZHAO ; Zhonggao XU ; Li ZHANG ; Hongyu CHEN ; Li LI ; Lihua WANG ; Yan YAN ; Yingchun MA ; Yuanyuan WEI ; Jingwei ZHOU ; Yan LI ; Caili WANG ; Jie DONG
Chinese Medical Journal 2025;138(21):2856-2858
4.A practice guideline for therapeutic drug monitoring of mycophenolic acid for solid organ transplants.
Shuang LIU ; Hongsheng CHEN ; Zaiwei SONG ; Qi GUO ; Xianglin ZHANG ; Bingyi SHI ; Suodi ZHAI ; Lingli ZHANG ; Liyan MIAO ; Liyan CUI ; Xiao CHEN ; Yalin DONG ; Weihong GE ; Xiaofei HOU ; Ling JIANG ; Long LIU ; Lihong LIU ; Maobai LIU ; Tao LIN ; Xiaoyang LU ; Lulin MA ; Changxi WANG ; Jianyong WU ; Wei WANG ; Zhuo WANG ; Ting XU ; Wujun XUE ; Bikui ZHANG ; Guanren ZHAO ; Jun ZHANG ; Limei ZHAO ; Qingchun ZHAO ; Xiaojian ZHANG ; Yi ZHANG ; Yu ZHANG ; Rongsheng ZHAO
Journal of Zhejiang University. Science. B 2025;26(9):897-914
Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C0), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug-drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage*
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Drug Monitoring/methods*
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Humans
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Organ Transplantation
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Immunosuppressive Agents/administration & dosage*
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Delphi Technique
5.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
6.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: A resting-state functional magnetic resonance imaging study.
Xuan YIN ; Xiao-Ling ZENG ; Jing-Jing LIN ; Wen-Qing XU ; Kai-Yu CUI ; Xiu-Tian GUO ; Wei LI ; Shi-Fen XU
Journal of Integrative Medicine 2025;23(2):159-168
OBJECTIVE:
Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA.
METHODS:
Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment.
RESULTS:
Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex.
CONCLUSION
EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals
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Electroacupuncture
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Male
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Magnetic Resonance Imaging
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Depression/diagnostic imaging*
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Mice, Inbred C57BL
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Brain/diagnostic imaging*
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Disease Models, Animal
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Mice
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Pain/diagnostic imaging*
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Acupuncture Points
7.Analysis of epidemiological and clinical characteristics of 1247 cases of infectious diseases of the central nervous system
Jia-Hua ZHAO ; Yu-Ying CEN ; Xiao-Jiao XU ; Fei YANG ; Xing-Wen ZHANG ; Zhao DONG ; Ruo-Zhuo LIU ; De-Hui HUANG ; Rong-Tai CUI ; Xiang-Qing WANG ; Cheng-Lin TIAN ; Xu-Sheng HUANG ; Sheng-Yuan YU ; Jia-Tang ZHANG
Medical Journal of Chinese People's Liberation Army 2024;49(1):43-49
Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6%),Mycobacterium tuberculosis 249(20.0%),other bacteria 150(12.0%),fungi 68(5.5%),parasites 18(1.4%),Treponema pallidum 18(1.4%)and rickettsia 1(0.1%).The number of cases increased by 177 cases(33.1%)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ¥29,500(¥16,000,¥59,200).The mortality rate from CNS infectious diseases is 1.6%.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.
8.Effects of electroacupuncture with"Zhi San Zhen"on Notch signaling pathway and synaptic plasticity in 5xFAD mice
Huaneng WEN ; Run LIN ; Yixiao WANG ; Bingshui WANG ; Lu LIU ; Chuanyao LIU ; Canxin CAI ; Shaoyang CUI ; Mingzhu XU
Chinese Journal of Tissue Engineering Research 2024;28(32):5148-5153
BACKGROUND:Alzheimer's disease is a degenerative neurological disorder characterized primarily by cognitive impairment.Acupuncture is a kind of traditional Chinese medicine therapy for treating Alzheimer's disease,but its mechanism is not yet clear. OBJECTIVE:To observe the effects of electroacupuncture with"Zhi San Zhen"on the Notch signaling pathway,β-amyloid protein(Aβ)and synaptic plasticity in 5xFAD mice. METHODS:Sixteen male,6-month-old 5xFAD mice,SPF-grade,were randomly divided into the electroacupuncture with"Zhi San Zhen"group(electroacupuncture group)and the model group,with eight mice in each group.Eight SPF-grade,male,6-month-old C57BL/6 mice were used as the wild control(wild)group.The electroacupuncture group received electroacupuncture with"Zhi San Zhen"intervention,5 times a week for 4 consecutive weeks.The model group and the wild group did not receive electroacupuncture intervention.The Morris water maze was used to preliminarily assess their learning and memory abilities.Thioflavin S staining was performed to detect Aβ plaque deposition.Western blot and real-time quantitative polymerase chain reaction(RT-qPCR)were used to measure the expression levels of transmembrane receptor protein Notch-1,Notch 1 intracellular domain(NICD),hairy and enhancer of split 1(Hes 1),hairy and enhancer of split 5(Hes 5),synaptophysin(SYN),postsynaptic density protein-95(PSD-95),and Aβ. RESULTS AND CONCLUSION:Compared with the model group,the wild group and the electroacupuncture group showed shortened escape latency,increased platform crossing times,and longer target quadrant dwell time(P<0.05).Compared with the wild group,the model group had significantly increased deposition of Aβ plaques,while electroacupuncture with"Zhi San Zhen"inhibited the deposition of Aβ plaques in the hippocampus of 5xFAD mice(P<0.05).Compared with the wild group,the model group had decreased mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased mRNA levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"increased the mRNA levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue,and decreased the mRNA level of Aβ(P<0.05).Compared with the Wild group,the model group had decreased protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5 in the hippocampal tissue of mice,and increased protein expression levels of Aβ(P<0.05).Electroacupuncture with"Zhi San Zhen"upregulated the protein expression levels of SYN,PSD-95,Notch 1,NICD,Hes 1,and Hes 5,and inhibited the protein expression of Aβ(P<0.05).To conclude,electroacupuncture with"Zhi San Zhen"can improve the learning and memory abilities of 5xFAD mice,possibly by inhibiting the deposition of Aβ protein and activating the Notch signaling pathway in the hippocampus to enhance synaptic plasticity.
9.Establishment and validation of a laboratory-based multiparameter model for predicting bone marrow metastasis in malignant tumors
Haocheng LI ; Wei XU ; Zhonghua DU ; Lin SONG ; Dan LIU ; Huihui SHAO ; Chunhe ZHAO ; Weiqi CUI ; Linlin QU
Chinese Journal of Laboratory Medicine 2024;47(11):1248-1255
Objective:To establish and validate the prediction model for bone marrow metastasis (BMM) in malignant tumors by screening out laboratory multiparameters.Methods:This case-control study collected 444 cases of malignant tumor patients who were hospitalized in the First Hospital of Jilin University from March 2018 to March 2024, including 243 cases for model establishment set and 201 cases for model validation set. The model establishment set was divided into BMM positive group (81 cases) and BMM negative group (162 cases), and the model validation set was divided into positive group (67 cases) and a negative group (134 cases). We collected patients′ clinical information such as gender, age, clinical diagnosis, and results of 47 laboratory tests including routine blood analysis, coagulation, liver function, tumor markers, potassium, sodium, chloride, and calcium ion tests, bone marrow morphology, and bone marrow biopsy. BMM was taken as the outcome event, differencial variables were analyzed using inter group comparisons, the correlation among parameters was analyzed using Pearson correlation analysis, the risk factors for BMM were analyzed using multivariate conditional logistic regression analysis, to establish logistic model, followed by efficiency evaluation on BMM predictive model using receiver operating characteristic (ROC) curves.Results:In the model establishment set, Pearson correlation analysis of 28 parameters that differed between the BMM positive and negative groups revealed that the correlation coefficients of 17 parameters, including mean platelet volume (MPV), hematocrit (HCT), hemoglobin (HGB), and prothrombin time (PT), were no more than 0.6 ( P<0.05). Further multivariate conditional logistic regression analysis demonstrated that MPV, HGB, HCT, PT, red cell distribution width (RDW), platelet count (PLT), alkaline phosphatase (ALP), chloride (Cl -), and mean erythrocyte hemoglobin concentration (MCHC) were the risk factors of BMM occurence in malignancy [MPV ( OR=9.929, 95% CI 2.688-71.335), HCT ( OR=8.232, 95% CI 6.223-9.841), HGB ( OR=4.300, 95% CI 1.947-16.577), PT ( OR=3.738, 95% CI 1.359-11.666), RDW ( OR=1.995, 95% CI 1.275-3.807), ALP ( OR=1.025, 95% CI 1.012-1.045), PLT ( OR=1.014, 95% CI 1.002-1.031), MCHC ( OR=0.724, 95% CI 0.523-0.880) and Cl -( OR=0.703, 95% CI 0.472-0.967)]. In the model establishment set, combiation of risk factors provided an AUC of 0.943 (95% CI 0.898-0.987, P<0.001), a sensitivity of 86.3%, and a specificity of 89.2% for BMM prediction. In the model validation set, the AUC was 0.924 (95% CI 0.854-0.960, P<0.001), with a sensitivity and specificity of 86.7% and 83.8%, respectively. Conclusion:This study built and validated a multiple-parameter model for BMM, which may facilitate the timely detection of BMM and provide reference for decision making of bone marrow aspiration.
10.Study on the predictive value of uterine artery ultrasound parameters combined with four coagulation indicators test for placental abruption in late pregnancy
Honglian ZHAO ; Cui LI ; Jie XU ; Ping LIN
Chinese Journal of Endocrine Surgery 2024;18(5):733-738
Objective:To explore the predictive value of uterine artery ultrasound parameters combined with four coagulation indicators test for placental abruption in late pregnancy.Methods:A total of 160 pregnant women with placental abruption during the late pregnancy who were diagnosed and treated in our hospital from Jan. 2021 to Dec. 2022 were collected as the observation group, and 160 pregnant women with normal delivery were regarded as the control group. According to different grading of placental abruption, 65 cases were classified as grade I, 54 cases as grade II, and 41 cases as grade III. Ultrasound parameters of uterine artery [uterine artery pulsatility index (PI), resistance index (RI), ratio of maximum systolic blood flow velocity (S) to maximum diastolic blood flow velocity (D) (S/D) ], and four coagulation parameters [prothrombin time (PT), fibrinogen (FIB), thrombin time (TT), and activated partial thromboplastin time (APTT) ] were compared; Logistic regression analysis was conducted to analyze the factors affecting placental abruption in late pregnancy; receiver operating characteristic (ROC) curve was applied to analyze the predictive value of uterine artery ultrasound parameters combined with four coagulation indicators test for placental abruption in late pregnancy.Results:Compared with the control group, PI, RI, and S/D ratios of pregnant women with placental abruption in the late pregnancy in the observation group were obviously increased [ (1.26 ± 0.22) vs. (0.95 ± 0.14), (0.65 ± 0.12) vs. (0.48 ± 0.06), (3.46 ± 0.63) vs. (2.57 ± 0.45) ] (P<0.05) ; compared with the control group, PT, TT, and APTT in pregnant women with placental abruption in the late pregnancy in the observation group were obviously increased [ (12.90 ± 1.42) vs. (10.24 ± 1.14), (15.06 ± 1.24) vs. (12.67 ± 1.08), (30.32 ± 2.55) vs. (25.48 ± 2.10) ] ( P<0.05), the FIB level was obviously decreased [ (3.09 ± 0.37) g/L vs. (3.96 ± 0.58) g/L] (P<0.05) ; compared with the grade I group, as the grading of placental abruption increased, PI, RI, S/D ratio, PT, TT, and APTT in grade II group and grade III group increased in turn ( P<0.05) and the level of FIB decreased in turn ( P<0.05) ; Logistic regression analysis showed that mechanical injury, polyhydramnios, premature rupture of membranes, pregnancy diabetes, pregnancy induced hypertension, PI, RI, S/D ratio, PT, TT, APTT were the risk factors for placental abruption in late pregnancy ( P<0.05), and FIB was the protective factor for placental abruption in late pregnancy ( P<0.05) ; the area under the ROC curve (AUC) the combined detection of PI, RI, S/D ratio, PT, FIB, TT, and APTT for placental abruption in late pregnancy was 0.982, which was better than their individual predictions (Z combined test-PI=6.118, P<0.001; Z combined test-RI=6.080, P<0.001; Z combined test-S/D ratio=6.690, P<0.001; Z combined test-PT=5.837, P<0.001; Z combined test-FIB=6.500, P<0.001; Z combined test-TT=6.439, P<0.001; Z combined test- PTT=6.112, P<0.001) . Conclusions:The PI, RI, S/D ratio, PT, TT, APTT increase, and FIB level decreases in pregnant women with placental abruption in the late pregnancy, they are related to different grades of placental abruption. Combined detection has good predictive value for placental abruption in pregnant women in the late pregnancy.

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