Objective:To establish reference values for clot waveform analysis (CWA) and analyze their diagnostic efficacy in distinguishing acquired hemophilia A (AHA) and lupus anticoagulant (LA)-positive patients.Methods:Case-Control Study. A total of 391 healthy individuals(260 males and 131 females) with a mean age of 45.53±14.85 years were enrolled at Nanyang central Hospital between January 6, 2023 and October 10, 2024. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were measured to establish reference ranges for the CWA parameters, including maximal reaction velocity (Min1), maximal reaction acceleration (Min2), and maximal reaction deceleration (Max2). A total of 158 definitively diagnosed AHA and LA-positive patients (mean age:42.46±14.83 years), including 34 AHA patients and 124 LA-positive patients, were recruited. The Mann Whitney U test was used to analyze the differences in the CWA parameters between the two groups. The diagnostic efficacy of CWA parameters in distinguishing AHA and LA-positive patients was evaluated using the area under the receiver operating characteristic(ROC) curve AUC and the cut-off values were calculated. Results:The reference values for PT-Min1, APTT-Min1, APTT-Min2, APTT-Max2, TT-Min1, TT-Min2, TT-Max2 were 203.41-516.89, 144.63-324.03, 526.46-1 190.03, -404.96±157.22, 159.17±60.34, 272.29-686.99, and -289.47--113.76, respectively. Compared with the CWA parameters in AHA patients, APTT-Max2 was significantly lower in LA-positive patients [-422.74(-577.50, -239.22) vs. -68.87(-92.85,30.28), Z=-7.43, P<0.01], while PT-Min1, APTT-Min1, APTT-Min2, TT-Min1, TT-Min2 were significantly elevated [287.01(188.03, 382.50) vs. 107.45(90.20, 151.39), 972.88(601.20, 1 351.19) vs. 229.10(118.38, 371.67), Z=6.68, 6.69, all P<0.01]. ROC analysis demonstrated the APTT-CWA parameter exhibited high diagnostic efficacy in patients with AHA (AUC>0.900 for both).Additionally, APTT-Min1 and APTT-Max2 were found to be useful in distinguishing between AHA patients and those with LA-positive status accompanied by APTT prolongation (AUC=0.660, 0.700, respectively). Conclusions:Reference values for CWA parameters were successfully established. The APTT-CWA is useful for differentiating between AHA and LA-positive patients and APTT-Max2 demonstrated a good diagnostic value in differentiating AHA patients from those with LA-positive status accompanied by APTT prolongation.

Objective:To establish reference values for clot waveform analysis (CWA) and analyze their diagnostic efficacy in distinguishing acquired hemophilia A (AHA) and lupus anticoagulant (LA)-positive patients.Methods:Case-Control Study. A total of 391 healthy individuals(260 males and 131 females) with a mean age of 45.53±14.85 years were enrolled at Nanyang central Hospital between January 6, 2023 and October 10, 2024. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were measured to establish reference ranges for the CWA parameters, including maximal reaction velocity (Min1), maximal reaction acceleration (Min2), and maximal reaction deceleration (Max2). A total of 158 definitively diagnosed AHA and LA-positive patients (mean age:42.46±14.83 years), including 34 AHA patients and 124 LA-positive patients, were recruited. The Mann Whitney U test was used to analyze the differences in the CWA parameters between the two groups. The diagnostic efficacy of CWA parameters in distinguishing AHA and LA-positive patients was evaluated using the area under the receiver operating characteristic(ROC) curve AUC and the cut-off values were calculated. Results:The reference values for PT-Min1, APTT-Min1, APTT-Min2, APTT-Max2, TT-Min1, TT-Min2, TT-Max2 were 203.41-516.89, 144.63-324.03, 526.46-1 190.03, -404.96±157.22, 159.17±60.34, 272.29-686.99, and -289.47--113.76, respectively. Compared with the CWA parameters in AHA patients, APTT-Max2 was significantly lower in LA-positive patients [-422.74(-577.50, -239.22) vs. -68.87(-92.85,30.28), Z=-7.43, P<0.01], while PT-Min1, APTT-Min1, APTT-Min2, TT-Min1, TT-Min2 were significantly elevated [287.01(188.03, 382.50) vs. 107.45(90.20, 151.39), 972.88(601.20, 1 351.19) vs. 229.10(118.38, 371.67), Z=6.68, 6.69, all P<0.01]. ROC analysis demonstrated the APTT-CWA parameter exhibited high diagnostic efficacy in patients with AHA (AUC>0.900 for both).Additionally, APTT-Min1 and APTT-Max2 were found to be useful in distinguishing between AHA patients and those with LA-positive status accompanied by APTT prolongation (AUC=0.660, 0.700, respectively). Conclusions:Reference values for CWA parameters were successfully established. The APTT-CWA is useful for differentiating between AHA and LA-positive patients and APTT-Max2 demonstrated a good diagnostic value in differentiating AHA patients from those with LA-positive status accompanied by APTT prolongation.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

Objective:To observe any effect of environmental enrichment on depressive behavior and the expression of the neuroplasticity-related protein kinase A (PKA), cAMP response element binding protein (CREB), phosphorylated CREB (p-CREB), and brain-derived neurotrophic factor (BDNF) in rats subjected to chronic, unpredictable mild stress (CUMS).Methods:Forty male Sprague-Dawley rats were divided at random into a blank group, a model control group, a no-music-environmental enrichment (NMEE) group and a music-environmental enrichment (MEE) group, each of 10. CUMS was induced in all except the blank group. After successful modeling, the rats in the blank and model control groups were housed in conventional cages for 21 days, while the MEE group received 21 days of environmental enrichment with music and the NMEE group was similarly housed without the music. After the intervention, all groups underwent a sugar water preference experiment, an open field experiment, and a forced swimming experiment. They were then sacrificed and hippocampal PKA, CREB, p-CREB and BDNF protein expressions were detected using immunohistochemistry and western blotting.Results:After the intervention there were significant differences between the model control and blank groups in their sugar water preference, the total distance of their open field activities, the central area distance of their activities, their time spent standing up, and the duration of immobility during swimming. Those indicators were also significantly different between the MEE and model control groups. The average duration of swimming immobility of the NMEE group was significantly longer than the MEE group′s average. The percentage the hippocampus positive for CREB, p-CREB or BDNF protein had decreased significantly in the model control group compared to the blank group, while those percentages in the NMEE and especially the MEE group were significantly different from those of the model control group. PKA, CREB, p-CREB and BDNF protein expression in the model control group was significantly different from that in the blank group, while those levels in the NMEE group were significantly higher than in the model control group on average. The levels in the MEE group were the highest of all.Conclusions:Environmental enrichment can significantly improve depressive behavior resulting from CUMS, at least in rats. Adding music to an enriched environment can enhance its anti-depressant efficacy. The anti-depressant mechanism of environmental enrichment may be related to its upregulation of PKA, CREB, p-CREB and BDNF protein expression.

Objective:To observe any effect of environmental enrichment on depressive behavior and the expression of the neuroplasticity-related protein kinase A (PKA), cAMP response element binding protein (CREB), phosphorylated CREB (p-CREB), and brain-derived neurotrophic factor (BDNF) in rats subjected to chronic, unpredictable mild stress (CUMS).Methods:Forty male Sprague-Dawley rats were divided at random into a blank group, a model control group, a no-music-environmental enrichment (NMEE) group and a music-environmental enrichment (MEE) group, each of 10. CUMS was induced in all except the blank group. After successful modeling, the rats in the blank and model control groups were housed in conventional cages for 21 days, while the MEE group received 21 days of environmental enrichment with music and the NMEE group was similarly housed without the music. After the intervention, all groups underwent a sugar water preference experiment, an open field experiment, and a forced swimming experiment. They were then sacrificed and hippocampal PKA, CREB, p-CREB and BDNF protein expressions were detected using immunohistochemistry and western blotting.Results:After the intervention there were significant differences between the model control and blank groups in their sugar water preference, the total distance of their open field activities, the central area distance of their activities, their time spent standing up, and the duration of immobility during swimming. Those indicators were also significantly different between the MEE and model control groups. The average duration of swimming immobility of the NMEE group was significantly longer than the MEE group′s average. The percentage the hippocampus positive for CREB, p-CREB or BDNF protein had decreased significantly in the model control group compared to the blank group, while those percentages in the NMEE and especially the MEE group were significantly different from those of the model control group. PKA, CREB, p-CREB and BDNF protein expression in the model control group was significantly different from that in the blank group, while those levels in the NMEE group were significantly higher than in the model control group on average. The levels in the MEE group were the highest of all.Conclusions:Environmental enrichment can significantly improve depressive behavior resulting from CUMS, at least in rats. Adding music to an enriched environment can enhance its anti-depressant efficacy. The anti-depressant mechanism of environmental enrichment may be related to its upregulation of PKA, CREB, p-CREB and BDNF protein expression.

Objective: To analyze the disease burden and trend of attention deficit hyperactivity disorder (ADHD) in China from 1990 to 2019, so as to provide the basic theoretical basis for the health administrative departments to formulate policies. Methods: Using the 2019 Global Burden of Disease Database, the incidence, prevalence and disability adjusted life year (DALY) rates of ADHD were analyzed for both sex and different age groups, and the trends of ADHD were predicted. Results: In 2019, the incidence, prevalence and DALY rate of ADHD in China were 70.41/100 000, 1 546.15/100 000 and 18.87/100 000 respectively. Compared with 1990, the rates decreased by 27.30%, 25.35% and 55.80% respectively, and these rates of females were lower than those of males. In 2019, the incidence rate of ADHD was the highest in the age group 5-9 years old (837.76/100 000), while the highest prevalence and DALY rates were found in ages groups of 10-14 years old (5 740.47/100 000 and 70.49/100 000). The results of the Joinpoint regression model showed that the incidence, prevalence and DALY rate had a downward trend from 1990 to 2019. The AAPC was -1.35%, -1.16% and -1.16%, respectively, with a statistically significant difference ( P <0.05). The prediction results of grey prediction model GM (1,1) indicated that the incidence and prevalence rate of ADHD in China would decline from 2020 to 2030. Conclusion The burden of ADHD in China showed a decreasing trend from 1990 to 2019, indicating that the prevention and treatment effect of ADHD in children and adolescents of China was effective. China should take active preventive measures to reduce the burden of ADHD in children and adolescents.

Objective To explore the rules of acupoint selection and manipulation application of Tuina in the treatment of diabetes peripheral neuropathy(DPN)with data mining technology.Methods The clinical research literature of Tuina for DPN from October 2022 was selected by searching four Chinese databases that CNKI,WanFang,VIP and Chinese Biomedical Literature Database.Using the traditional Chinese medicine inheritance assistance platform software,analyze and summarize the rules of selecting acupoints and applying manipulations in the treatment of DPN with Tuina.Results A total of 110 articles were included,including 65 acupoints and 33 manipulations.The acupoints with the highest frequency are Zusanli(ST 36),Sanyinjiao(SP 6),Taixi(KI 3),Yongquan(KI 1),Taichong(LR 3),Yanglingquan(GB 34),etc.The meridians mainly include Taiyin Spleen Meridian of Foot,Yangming Stomach Meridian of Foot,Taiyang Bladder Meridian of Foot and Shaoyin Kidney Meridian of Foot.Five-shu Points,Lower He-sea Points and Yuan-primary Points are commonly used specific points.The acupoints are mostly distributed in the lower limbs.The categories of Tuina manipulations mainly include squeezing-pressing manipulations,pushing rolling manipulations and composite manipulations.The Tuina manipulations mainly include kneading manipulation,pressing manipulation,point-pressing manipulation,pressing-kneading manipulation and twisting manipulation with both palms.Conclusion The acupoint selection and manipulation application of Tuina in treating DPN have certain rules,and the main treatment principles are to regulate the organs and dredge collaterals,and to replenish qi and promote blood circulation,which can provide objective basis for clinical treatment.

Objective:To find out the occurrence of anxiety and depressive symptoms, and the major risk factors, and the participation rate, as well as the experience of medical personnel who are involved in the intervention.Methods:Since January 2018, a pilot intervention had been carried out on pregnant women registered in the antenatal clinic. The Generalized Anxiety Disorder Scale and the Patient Health Questionnaires were used as screening tools for anxiety and depression symptoms, and risk factors were screened too. Interventions were carried out on the psychological moderate and high risk women by obstetric medical staff and mental health personnel. A qualitative interview was conducted on the intervention providers.Results:A total of 9 488 pregnant women were included, and the positive rate of moderate anxiety symptoms was 3.0%, the positive rate of severe anxiety symptoms was 1.4%; the positive rate of moderate depression symptoms was 18.1%, and the positive rate of severe depressive symptoms was 5.2%; the comorbidity rate of anxiety and depression symptoms was 3.4%. The first three risk factors for pregnant women with anxiety symptoms were: once had premenstrual stress symptom, excessive fear of fetal growth, previous abnormal maternal history; the first three risk factors for pregnant women with depressive symptoms: once had premenstrual stress symptom, previous abnormal maternal history, this pregnancy was cherished; the first three risk factors for pregnant women with moderate and above anxiety combined with depression were: once had premenstrual stress symptom, excessive fear of fetal growth, and fear the delivery process is not successful. Among the psychological moderate risk pregnant women, 19.1% participated in the midwife joint counselor clinic, and 1.7% participated in the obstetrician joint psychological specialist nurse clinic, 2.2% of the pregnant women with high risk participated in the psychological multidisciplinary consultation, and 1.7% referred to the psychiatric department. From the interviews, providers believed that it was necessary to further strengthen the ability of psychological intervention capacity, and the psychological screening tools needed to be improved, and the problems sought by pregnant women involved in physical, psychological and social aspects, and the influence of pregnant women's treatment compliance included multiple factors.Conclusions:The psychological health care service during pregnancy was feasible, but the screening scales needed further examination. The mental health care ability of obstetric medical staff needed to be strengthened, and the compliance of pregnant women with mental health services needed to be improved.

Objective: To summarize the clinical features of 7 rare cases of hemolytic disease of newborn (HDN), and to improve the understanding of rare HDN. Methods: Data of clinical information, laboratory findings, treatments and outcomes were collected and analyzed for four cases with HDN due to anti-M, two cases due to anti-Kidd, and one case due to anti-Duffy. All of them were admitted to the Department of Neonatology, Beijing Children's Hospital Affiliated to Capital Medial University from July 2007 to June 2017. Results: Among the four MN hemolytic babies, two were males and two were females. Jaundice was found in three cases. Two cases had hyperbilirubinemia, one of them had severe hyperbilirubinemia. All the four cases developed anemia, including severe anemia in three cases. Two cases of Kidd hemolytic disease and 1 case of Duffy hemolytic disease had jaundice and anemia, but did not reach the level of severe hyperbilirubinemia and severe anemia. MN hemolytic disease babies got negative results in direct antiglobulin test, whereas the Kidd and Duffy hemolytic disease babies had positive findings in direct antiglobulin test. None of the babies had blood transfusion, and they were discharged from the hospital. Conclusions Without maternal and fetal blood group incompatibility (ABO or Rh blood-group system), for early onset of jaundice, severe jaundice or anemia, antiglobulin test to mother and child earlier should be administered, and MN, Kidd, Duffy and other rare hemolytic disease of the newborn should be pay attention to.

Objective: To explore the effect of heme oxygenase-1 (HO-1) on level of reactive oxygen species (ROS) induced by zinc oxide nanoparticles (ZnO-NPs) in Human umbilical vein endothelial cells line EA.hy926. Methods: The EA.hy926 cells in logarithmic growth phase were incubated with 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs respectively. The ROS level, reflected by mean fluorescence intensity (MFI), was examined by flow cytometer after 4 hours exposure, the protein expression of HO-1 which was determined by Western Blot after exposed to ZnO-NPs for 24 hours. Cells incubated with 15.0 mg/L were set as the ZnO-NPs group; a blank control group was set at the same time. Cells were pretreated with HO-1 inhibitor zinc protoporphyrin (ZnPPIx) and HO-1 activator cobalt protoporphyrin (CoPPIx), they were classified as ZnPPIx group and CoPPIx group. 15 mg/L ZnO-NPs was chosen to conduct the experiment of HO-1 activation and inhibition. Cells were classified as ZnPPIX+ ZnO-NPs group and CoPPIx+ ZnO-NPs group after pretreated with 10 μmol/L ZnPPIx or CoPPIx for 1 h, added 15 mg/L ZnO-NPs to cell culture medium. In all groups ROS levels were detected after exposed to ZnO-NPs for 4 hours, the protein expression of HO-1 was detected after exposed to ZnO-NPs for 24 hours. Results: With the increased dose of ZnO-NPs, levels of ROS and HO-1 in EA.hy926 cells were clearly elevated (the MFI of 0.0, 2.5, 5.0, 10.0 and 15.0 mg/L ZnO-NPs incubated groups was 22 627.22±718.27, 24 726.47±568.52, 31 141.75±1 312.24, 39 824.82±4 774.74, 50 569.03±1 497.63 respectively, and HO-1 relative expression were 0.16±0.01, 0.19±0.02, 0.16±0.01, 0.23±0.02, 0.92±0.06 respectively). HO-1 expression in ZnPPIx pretreatment group decreased compared with ZnO-NPs group (1.05±0.05 vs. 1.12±0.01, P<0.05), meanwhile ROS level enhanced (62 683.95±2 589.59 vs. 53 654.53±2 229.01, P<0.05). However, CoPPIx pretreatment had higher HO-1 level and lower level of ROS compared with ZnO-NPs group (HO-1: 1.74±0.11 vs. 0.22±0.03, P<0.05; ROS: 32 845.04±993.48 vs. 53 654.53±2 229.01, P<0.05). Conclusions Exposure to ZnO-NPs significantly induced ROS generation in EA.hy926 cells in a dose-dependent manner. HO-1 regulated ZnO-NPs-induced oxidative stress.