Objective:To establish a dose-response curve of dicentric chromosomes and centromeric rings (dic+ r) in γ-ray irradiation-induced chromosomal aberrations in human peripheral blood lymphocytes through automated analysis.Methods:Peripheral blood samples from three healthy donors were irradiated in vitro at doses of 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, and 5 Gy and a dose rate of 0.80 Gy/min using a 137Cs γ-ray source. Post-irradiation, lymphocytes were cultured based on standard protocols, harvested using an automatic cell harvester, and prepared on slides using an automatic slide preparation system. dic+ r were analyzed fully automatically using the DCScore software, and a dose-response curve of dic+ r was established through fitting and then validated using the CABAS software. Results:The dose-response curve followed a linear-quadratic model, i. e., y = 0.093 65+ 0.030 21 D+ 0.025 31 D2 ( R2 = 0.999 2), where y was the quantity of dic+ r and D was the absorbed dose of γ-ray irradiation (Gy). Doses to samples for blind validation were estimated using this curve, yielding deviations of less than 24% from the actual irradiation doses. Conclusions:The fully automated analysis of dic+ r in 137Cs γ-ray irradiation-induced chromosomal aberrations, followed by the construction of the dose-response curve, holds significant potential for rapid, high-throughput biodosimetry in large-scale nuclear emergencies.

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.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Objective:To establish a dose-response curve of dicentric chromosomes and centromeric rings (dic+ r) in γ-ray irradiation-induced chromosomal aberrations in human peripheral blood lymphocytes through automated analysis.Methods:Peripheral blood samples from three healthy donors were irradiated in vitro at doses of 0, 0.5, 0.75, 1, 1.5, 2, 3, 4, and 5 Gy and a dose rate of 0.80 Gy/min using a 137Cs γ-ray source. Post-irradiation, lymphocytes were cultured based on standard protocols, harvested using an automatic cell harvester, and prepared on slides using an automatic slide preparation system. dic+ r were analyzed fully automatically using the DCScore software, and a dose-response curve of dic+ r was established through fitting and then validated using the CABAS software. Results:The dose-response curve followed a linear-quadratic model, i. e., y = 0.093 65+ 0.030 21 D+ 0.025 31 D2 ( R2 = 0.999 2), where y was the quantity of dic+ r and D was the absorbed dose of γ-ray irradiation (Gy). Doses to samples for blind validation were estimated using this curve, yielding deviations of less than 24% from the actual irradiation doses. Conclusions:The fully automated analysis of dic+ r in 137Cs γ-ray irradiation-induced chromosomal aberrations, followed by the construction of the dose-response curve, holds significant potential for rapid, high-throughput biodosimetry in large-scale nuclear emergencies.

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 examine the impact and partial mechanism of bupivacaine sustained-release drug(code PB21)in combination with low-dose dexamethasone(Dex)on the analgesic time of rats with knee osteoarthritis(KOA).Methods Using the techniques of anterior cruciate ligament transection and meniscus instability,a rat KOA model was created.After eight weeks,SD mice were split into three groups at random:a group for the model,one for Dex(50 μg),one for PB21(1.5 mg),and one for combined administration(1.5 mg PB21/50 μg Dex),with a control group that received a sham operation.The pain thresholds of KOA rats were measured using a Pres-sure Application Measurement(PAM)at different intervals before to delivery and 4,24,36,and 48 hours following administration;to gauge changes in discomfort,a CatWalk was used to assess the rats'average foot strength and maximum contact area before,four,twenty-four,and forty-eight hours after treatment.A portion of the rats were put to sleep at four,twenty-four,and forty-eight hours following the injection,and the joint synovium was removed for paraffin sectioning.Immunohistochemistry was used to identify the expression of GAP43 in the synovium,whereas immunofluorescence was used to identify the expression of CGRP in the same tissue.Results The average strength and maximum contact area of the foot and claw decreased(P＜0.01),and the pain threshold decreased(P＜0.01)in the model group compared to the sham operation group.The PB21+Dex group experienced a delayed pain threshold lowering time delay when compared to the PB21 and Dex treatment groups alone.Up to 48 hours lat-er,the combination administration group's average strength and maximum contact area of the foot paw remained ele-vated,and there was a statistically significant difference(P＜0.05)between the combined administration group and PB21 and Dex alone.GAP43 and CGRP expression levels in synovial tissue were detected.The results indica-ted that PB21 and Dex alone could lower protein expression levels at 4 and 24 h at the two time points,and that the PB21+Dex group could still significantly lower GAP43 and CGRP expression levels at 48 h.At the 48 h time point,the PB21+Dex group was statistically significant when compared to the PB21 and Dex alone administration group(P＜0.05).Conclusion In summary low dose dexamethasone can prolong the analgesic effect of PB21 on KOA rats,which is connected to reducing the expression of pain related proteins CGRP and GAP43.

Objective:To study the protective effects and mechanism of Melastoma sanguineum Sims fruit extract (MSE) on chronic chemical liver injury induced by ethanol, acetaminophen and carbon tetrachloride in mice; To discuss it mechanism.Methods:Totally 96 mice were divided into normal control group, ethanol model group, ethanol+bifendate control group and ethanol+MSE high-, medium- and low-dosage groups, APAP model group, APAP+bifendate control group and APAP+MSE high-, medium- and low-dosage groups, CCl 4 model group, CCl 4+bifendate control group and CCl 4+MSE high-, medium- and low-dosage groups, with 6 mice in each group. Except for the normal control group, the other groups were respectively prepared for the ethanol model, the APAP model and the CCl 4 model. The mice in the MSE high-, medium- and low-dosage groups were intragastrically administrated with 10, 5 and 2.5 g/kg of MSE, respectively; the bifendate control group was intraperitoneally injected with 15 mg/ml bifendate solution at 75 mg/kg; the normal control group was intraperitoneally injected with equal volume of normal saline/peanut oil solution once a day for 25 consecutive days. The levels of GPT, GOT and total bilirubin (TBIL) in serum were detected; the activities of SOD and GSH-Px and the content of MDA in liver tissue were detected; the mRNA expressions of TNF-α, IL-6, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were detected by qRT-PCR; the protein expressions of cytochrome P450 CYP1A1, CYP1A2, and CYP3A in liver tissue were detected by Western blot; the pathological changes of the liver tissue were observed by HE staining. Results:Compared with the corresponding ethanol, APAP and CCl 4 model groups, the serum GPT, GOT and TBIL levels of mice in the ethanol+bifendate control group and ethanol+MSE high- and medium-dosage groups, the APAP+bifendate control group and APAP+MSE high- and medium-dosage groups, and the CCl 4+bifendate control group and CCl 4+MSE high- and medium-dosage groups decreased ( P<0.01 or P<0.05), the activities of SOD and GSH-Px in the liver tissue increased ( P<0.01 or P<0.05), and the MDA level decreased ( P<0.01 or P<0.05), and the mRNA levels of IL-6 and TNF-α decreased ( P<0.01); the mRNA levels of ADH and ALDH in the ethanol+MSE high-, medium-, and low-dosage groups decreased ( P<0.01). Compared with the APAP model group, the expressions of CYP1A1 and CYP1A2 in the APAP+MSE groups increased ( P<0.01), and the expression of CYP3A protein decreased ( P<0.05); compared with the CCl 4 model group, the expressions of CYP1A1, CYP1A2 and CYP3A proteins in the CCl 4+MSE groups decreased ( P<0.05). Conclusion:MSE has a protective effect on chronic chemically-induced liver injury induced by ethanol, APAP, and CCl 4 in mice, and its mechanism may be related to antioxidant stress, inhibition of inflammatory response, and regulation of the expression of cytochrome P450-related enzymes.

Objective:To explore the barriers and facilitators of exercise rehabilitation in patients with atrial fibrillation (AF) after radiofrequency ablation.Methods:From March to August 2022, 285 patients with atrial fibrillation who underwent radiofrequency ablation within three months were recruited from the "Cloud Ward" of the Department of Cardiovascular of the First Affiliated Hospital with Nanjing Medical University by convenience sampling. The Cardiac Rehabilitation Barriers Scale (CRBS) and the Self-efficacy for Exercise Scale (SEE) were used to evaluate the barriers and self-efficacy of patients participating in exercise rehabilitation, respectively. Among them, 22 patients were subjected to semi-structured interviews to extract themes.Results:Among 285 patients with atrial fibrillation, 202 (70.88%) participated in exercise rehabilitation programs. Work/time conflicts, lack of cardiac rehabilitation knowledge, and health/physical function limitations affected the participation of patients in exercise rehabilitation ( P<0.05). Qualitative research extracted three themes that affected the patient's exercise rehabilitation, including capability, opportunity, and motivation. Conclusions:The participation of atrial fibrillation patients in exercise rehabilitation is influenced by multiple factors such as family responsibility, capability, motivation, and opportunity. Medical and nursing staff should comprehensively consider the above factors, develop targeted interventions from all aspects and multiple angles, so as to effectively improve the participation of patients in exercise rehabilitation.

【Objective】 To explore the value of thromboelastogram (TEG) in evaluating coagulation function of patients with liver cancer. 【Methods】 102 patients with liver cancer and 48 with hepatic hemangioma from Department of Hepatobiliary Surgery, Nanyang Central Hospital from August 2017 to September 2020 were retrospectively analyzed. TEG indicators (R, K, Angle, MA, CI, and G value) and routine coagulation indicators (Plt, PT, INR, APTT, FIB, and TT) of those patients and basic clinical data of liver cancer patients were collected, and the difference of detection parameters between the liver cancer group and liver hemangioma group was compared; The difference of TEG parameters in liver cancer patient subgroups was compared, and the correlation between TEG and routine coagulation tests in liver cancer patients was analyzed using Spearman rank correlation analysis. The sensitivity of the two detection methods in detecting the coagulation status of patients with liver cancer was compared. 【Results】 1) Compared with patients with hepatic hemangioma, Plts decreased significantly (166.6±108.824 vs 224.10±54.933, P<0.001), while PT, INR and APTT values increased significantly (13.12±2.052 vs 11.421±0.884, 1.156±0.191 vs 1.00±0.074, 29.977±5.333 vs 26.954±5.269, all P<0.05) in patients with liver cancer; MA and G values in patients with liver cancer were lower (56.991±11.574 vs 60.069±5.094, 7.667±4.682 vs 7.725±1.709, P<0.05); 2) Compared with newly diagnosed liver cancer patients, the Plt of re-diagnosed liver cancer patients decreased significantly(125.78±79.673 vs 188.86±116.437, P<0.05); the R and K value increased significantly (7.594±2.601 vs 6.058±1.739, 3.453±2.402 vs 2.438±1.990, all P<0.05), while the Angle, MA, CI and G value decreased significantly (53.897±12.288 vs 61.495±9.949, 53.556±11.407 vs 58.865±11.313, -3.494±4.253vs -0.836±3.180, 6.311±3.209 vs 8.406±5.191, all P<0.05); 3) There were significant differences in TEG parameters (R value excluded) between liver resection, transhepatic arterial chemoembolization and conservative treatment (P<0.05); 4) The R, K value of patients with liver cancer were negatively correlated with the Plt value, while the Angle, MA, CI, and G value were positively correlated with Plt value (P<0.001); the K value was negatively correlated with the Fib value, while the Angle, MA, CI, G value were positively correlated with Fib value (P<0.001); the R and K value were positively correlated with TT value, while the Angle and CI were negatively correlated with TT value (P<0.05); 5) The detection rate of hypocoagulability by TEG and routine coagulation testing was 18.63% (19/102) and 7.84%. 【Conclusion】 Compared with the newly diagnosed liver cancer patients, re-diagnosed liver cancer patients showed hypercoagulability. TEG can diagnose the coagulation abnormalties more sensitively, and help reduce the risk of bleeding.