Congenital blood group chimerism refers to the coexistence of two or more distinct blood types within an individual, resulting from the presence of hematopoietic cell populations with different genotypes. Consequently, red blood cells in such individuals may express different blood group antigens. Based on the timing and mechanism of formation, blood group chimerism can be classified as either congenital or acquired. Although congenital blood group chimerism is rare and involves complex mechanisms, it holds significant implications in transfusion medicine, transplantation, and obstetrics. This article reviews the formation mechanisms, detection methods, and clinical significance of congenital blood group chimerism in transfusion medicine. Particular emphasis is placed on the principles, advantages, and limitations of various detection techniques. Furthermore, the potential applications of these technologies in clinical diagnosis are discussed, providing a technical foundation for the development of precise transfusion strategies.

Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

Objective:To compare the dosimetric parameters under different incremental modes between intensity-modulated radiation therapy(IMRT)and volume rotation intensity-modulated therapy(VMAT)for the target area of large volume brain metastases(BMs),and to explore the better way of treating BMs based on hypofractionated stereotactic radiotherapy(HSRT)of linear accelerator.Methods:A total of 30 BMs patients who underwent IMRT at The 971th Hospital of Navy of the CPLA from 2020 to 2023 were selected.In the treatment planning system(TPS),three types of IMRT plans and VMAT plans were designed,which included uniformity plan(Planuniformity)of target area dose,uniform increased plan(Planuniform increased-dose)and incremental plan(Planincremental)within target area.In the inside of the target area,the target area of high dose(GTVh)was set,and Planuniform increased-dose and Planincremental were designed to aim at GTVh.The differences of the doses of three types of treatment plans included Planuniformity,Planuniform increased-dose and Planincremental,which were respectively designed by using IMRT and VMAT,were analyzed.The mean dose(Dmean)of the target area,the 50%and 2%exposed doses(D50%and D2%)of the target area were observed and compared.The conformity index(CI),homogeneity index(HI),gradient index(GI),and the volume percentage(V10 Gy-V40 Gy)that normal brain tissue received 10 Gy-40 Gy also were observed and compared.Results:Compared with Planuniformity of IMRT,the Dmean of GTV of Planuniform increased-dose and Planincremental of IMRT increased by 10.13%and 17.9%,with statistically significant differences(t=13.680,12.771,P＜0.05).D50%increased by 8.9%and 10.8%,with statistically significant differences(t=15.190,9.929,P＜0.05).D2%increased by 15.2%and 46.4%,with statistically significant differences(t=52.320,8.746,P＜0.05).There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of IMRT(P＞0.05).Compared with Planuniformity of VMAT,the Dmean of GTV of Planuniform increased-dose and Planincremental of VMAT increased by 10.53%and 21.23%,with statistically significant differences(t=18.641,15.461,P＜0.05),and D50%increased by 9.1%and 13.4%,with statistically significant differences(t=11.382,10.952,P＜0.05),and D2%increased by 16.4%and 48.8%,with statistically significant differences(t=56.471,8.685,P＜0.05),respectively.There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of VMAT(P＞0.05).The normal brain tissue V20 Gy,V30 Gy and V40 Gy of Planuniform increased-dose and Planincremental of IMRT were respectively less than those of VMAT,and the differences of them between IMRT and VMAT were significant(tPlan uniform increased-dose=2.112,2.215,2.444,tPlan incremental=2.323,2.939,3.145,P＜0.05).There were no statistically significant difference in D2%,Dmean,and D50%between IMRT and VMAT(P＞0.05).Conclusion:On the premise of ensuring the safety of normal brain tissue at the edge of the target area,the synchronously increasing of the central dose of the target area will not significantly increase the dose for normal brain tissue.Both IMRT and VMAT can meet the requirements of increment in the inside of the target area,and VMAT has slightly better increment and higher efficiency within target area.The incremental of VMAT target area is slightly better,which also has better efficiency,while the enhancement effect of the dose of target area of Planincremental is better than that of the Planuniform increased-dose.The Plan incremental of VMAT is more suitable for HSRT treatment for BMs.

Objective:To compare the dosimetric parameters under different incremental modes between intensity-modulated radiation therapy(IMRT)and volume rotation intensity-modulated therapy(VMAT)for the target area of large volume brain metastases(BMs),and to explore the better way of treating BMs based on hypofractionated stereotactic radiotherapy(HSRT)of linear accelerator.Methods:A total of 30 BMs patients who underwent IMRT at The 971th Hospital of Navy of the CPLA from 2020 to 2023 were selected.In the treatment planning system(TPS),three types of IMRT plans and VMAT plans were designed,which included uniformity plan(Planuniformity)of target area dose,uniform increased plan(Planuniform increased-dose)and incremental plan(Planincremental)within target area.In the inside of the target area,the target area of high dose(GTVh)was set,and Planuniform increased-dose and Planincremental were designed to aim at GTVh.The differences of the doses of three types of treatment plans included Planuniformity,Planuniform increased-dose and Planincremental,which were respectively designed by using IMRT and VMAT,were analyzed.The mean dose(Dmean)of the target area,the 50%and 2%exposed doses(D50%and D2%)of the target area were observed and compared.The conformity index(CI),homogeneity index(HI),gradient index(GI),and the volume percentage(V10 Gy-V40 Gy)that normal brain tissue received 10 Gy-40 Gy also were observed and compared.Results:Compared with Planuniformity of IMRT,the Dmean of GTV of Planuniform increased-dose and Planincremental of IMRT increased by 10.13%and 17.9%,with statistically significant differences(t=13.680,12.771,P＜0.05).D50%increased by 8.9%and 10.8%,with statistically significant differences(t=15.190,9.929,P＜0.05).D2%increased by 15.2%and 46.4%,with statistically significant differences(t=52.320,8.746,P＜0.05).There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of IMRT(P＞0.05).Compared with Planuniformity of VMAT,the Dmean of GTV of Planuniform increased-dose and Planincremental of VMAT increased by 10.53%and 21.23%,with statistically significant differences(t=18.641,15.461,P＜0.05),and D50%increased by 9.1%and 13.4%,with statistically significant differences(t=11.382,10.952,P＜0.05),and D2%increased by 16.4%and 48.8%,with statistically significant differences(t=56.471,8.685,P＜0.05),respectively.There were no statistically significant differences in normal brain tissue V10 Gy-V40 Gy among Planuniformity,Planuniform increased-dose and Planincremental of VMAT(P＞0.05).The normal brain tissue V20 Gy,V30 Gy and V40 Gy of Planuniform increased-dose and Planincremental of IMRT were respectively less than those of VMAT,and the differences of them between IMRT and VMAT were significant(tPlan uniform increased-dose=2.112,2.215,2.444,tPlan incremental=2.323,2.939,3.145,P＜0.05).There were no statistically significant difference in D2%,Dmean,and D50%between IMRT and VMAT(P＞0.05).Conclusion:On the premise of ensuring the safety of normal brain tissue at the edge of the target area,the synchronously increasing of the central dose of the target area will not significantly increase the dose for normal brain tissue.Both IMRT and VMAT can meet the requirements of increment in the inside of the target area,and VMAT has slightly better increment and higher efficiency within target area.The incremental of VMAT target area is slightly better,which also has better efficiency,while the enhancement effect of the dose of target area of Planincremental is better than that of the Planuniform increased-dose.The Plan incremental of VMAT is more suitable for HSRT treatment for BMs.

Objective:To explore the application value of the combination of failure mode and effects analysis (FMEA) and work breakdown structure (WBS) on management of telemetry monitoring system. Methods:Seven sets of used telemetry monitoring systems in Huzhou Third People's Hospital from March 2022 to April 2024 were selected. The routine mode was used to manage the telemetry monitoring systems from March 2022 to February 2023,and the management mode of telemetry monitoring systems based on FMEA and WBS was adopted to manage the telemetry monitoring systems from May 2023 to April 2024. FMEA method was used to analyze the quantitative risk scores of various failures in 1740 uses of the telemetry monitoring system from March 2022 to February 2023,and the fault type was represented by Fx. According to the risk quantification score,the top 5 failure types included poor radio frequency (RF) signal (F2),larger pseudo-interference (F3) of electrocardiogram (ECG),abnormal measurement of blood oxygen saturation (SpO2) (F6),excessive movement and mistake touch (F8) of patients,and identification (ID) number error (F9) of telemetry emission box. WBS quality management method combined with tree chart,countermeasure fishbone chart,task assignment matrix and other tools were performed to conduct the setting of expected objectives,countermeasure analysis,task formulation and work implementation of management of telemetry monitoring system. The above indicators were compared with the changes of the top 5 failure risk grading and incidence of failure in 1850 uses of management of telemetry monitoring system from May 2023 to April 2024. Results:After the telemetry monitoring system was used to conduct management,the risk grading of the F2,F3,F6,F8 and F9 failures with highest risk grading reduced respectively to low grade,middle grade,middle grade,low grade and middle grade. At the same time,the number of F2,F3,F6,F8,F9 failures with the highest risk grading and total failures were respectively 91,89,39,45,39 and 478 times,and the incidence rates of them were 4.92％,4.81％,2.11％,2.43％,2.11％ and 25.84％,which were significantly lower than those of adopting conventional management methods. The differences of them between two methods were statistically significant (x2=2.125,6.911,9.099,2.261,2.431,32.491,P<0.05). Conclusion:The management of combined quality management method of FMEA and WBS for telemetry monitoring system can reduce risk grading and incidence rate of equipment failure,and ensure the safety of equipment in clinical use.

Objective:To explore the application value of the combination of failure mode and effects analysis (FMEA) and work breakdown structure (WBS) on management of telemetry monitoring system. Methods:Seven sets of used telemetry monitoring systems in Huzhou Third People's Hospital from March 2022 to April 2024 were selected. The routine mode was used to manage the telemetry monitoring systems from March 2022 to February 2023,and the management mode of telemetry monitoring systems based on FMEA and WBS was adopted to manage the telemetry monitoring systems from May 2023 to April 2024. FMEA method was used to analyze the quantitative risk scores of various failures in 1740 uses of the telemetry monitoring system from March 2022 to February 2023,and the fault type was represented by Fx. According to the risk quantification score,the top 5 failure types included poor radio frequency (RF) signal (F2),larger pseudo-interference (F3) of electrocardiogram (ECG),abnormal measurement of blood oxygen saturation (SpO2) (F6),excessive movement and mistake touch (F8) of patients,and identification (ID) number error (F9) of telemetry emission box. WBS quality management method combined with tree chart,countermeasure fishbone chart,task assignment matrix and other tools were performed to conduct the setting of expected objectives,countermeasure analysis,task formulation and work implementation of management of telemetry monitoring system. The above indicators were compared with the changes of the top 5 failure risk grading and incidence of failure in 1850 uses of management of telemetry monitoring system from May 2023 to April 2024. Results:After the telemetry monitoring system was used to conduct management,the risk grading of the F2,F3,F6,F8 and F9 failures with highest risk grading reduced respectively to low grade,middle grade,middle grade,low grade and middle grade. At the same time,the number of F2,F3,F6,F8,F9 failures with the highest risk grading and total failures were respectively 91,89,39,45,39 and 478 times,and the incidence rates of them were 4.92％,4.81％,2.11％,2.43％,2.11％ and 25.84％,which were significantly lower than those of adopting conventional management methods. The differences of them between two methods were statistically significant (x2=2.125,6.911,9.099,2.261,2.431,32.491,P<0.05). Conclusion:The management of combined quality management method of FMEA and WBS for telemetry monitoring system can reduce risk grading and incidence rate of equipment failure,and ensure the safety of equipment in clinical use.

Objective:To analyze the significance of ultrasound super microvascular imaging (SMI) combined with strain ratio (SR) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 110 patients with breast masses (110 lesions) admitted to Jiande Branch of the Second Affiliated Hospital of Zhejiang University from October 2022 to November 2024 were retrospectively selected, including 65 benign masses (benign group) and 45 malignant masses (malignant group). Both groups received SMI and strain elastography (SE) examination. The clinical and ultrasonic parameters SMI blood flow signal grade, vascular index (VI), global SR (ESR), local SR (LSR) and other indicators of the two groups were compared, and the independent risk of breast tumor malignancy was screened by Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the value of SMI blood flow signal grading, VI and ESR combined detection in the differential diagnosis of breast tumor malignancy.Results:The proportion of irregular shape, unclear boundary, microcalcification, convergence sign and angulation sign in the malignant group were higher than those in the benign group: 80.00%(36/45) vs. 55.38%(36/65), 57.78%(26/45) vs. 33.85%(22/65), 44.44%(20/45) vs. 13.85%(9/65), 55.56%(25/45) vs. 9.23%(6/65), 60.00%(27/45) vs. 15.38%(10/65), there were statistical differences ( P<0.05). The SMI blood flow signal grade in the malignant group was higher than that in the benign group, the VI, ESR and LSR in the malignant group were higher than those in the benign group: (6.53 ± 0.68)% vs. (3.14 ± 0.36)%, 4.62 ± 0.48 vs. 2.53 ± 0.27, 31.45 ± 3.29 vs. 20.16 ± 2.35, there were statistical differences ( P<0.05). Logistic regression analysis showed that irregular shape, unclear boundary, microcalcification, SMI blood flow signal grade, VI and ESR were independent risk factors for malignant breast mass ( P<0.05). ROC curve analysis results showed that the sensitivity, specificity and accuracy of SMI blood flow signal classification, VI and ESR combined in predicting breast tumor malignancy were 84.26%, 83.17% and 87.65%, respectively, and the area under the curve was 0.896, which were higher than the results predicted by each index alone. Conclusions:There are certain characteristic changes of SMI in benign and malignant breast masses. SMI combined with SR has good value in differential diagnosis of benign and malignant breast masses.

Objective:To analyze the significance of ultrasound super microvascular imaging (SMI) combined with strain ratio (SR) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 110 patients with breast masses (110 lesions) admitted to Jiande Branch of the Second Affiliated Hospital of Zhejiang University from October 2022 to November 2024 were retrospectively selected, including 65 benign masses (benign group) and 45 malignant masses (malignant group). Both groups received SMI and strain elastography (SE) examination. The clinical and ultrasonic parameters SMI blood flow signal grade, vascular index (VI), global SR (ESR), local SR (LSR) and other indicators of the two groups were compared, and the independent risk of breast tumor malignancy was screened by Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the value of SMI blood flow signal grading, VI and ESR combined detection in the differential diagnosis of breast tumor malignancy.Results:The proportion of irregular shape, unclear boundary, microcalcification, convergence sign and angulation sign in the malignant group were higher than those in the benign group: 80.00%(36/45) vs. 55.38%(36/65), 57.78%(26/45) vs. 33.85%(22/65), 44.44%(20/45) vs. 13.85%(9/65), 55.56%(25/45) vs. 9.23%(6/65), 60.00%(27/45) vs. 15.38%(10/65), there were statistical differences ( P<0.05). The SMI blood flow signal grade in the malignant group was higher than that in the benign group, the VI, ESR and LSR in the malignant group were higher than those in the benign group: (6.53 ± 0.68)% vs. (3.14 ± 0.36)%, 4.62 ± 0.48 vs. 2.53 ± 0.27, 31.45 ± 3.29 vs. 20.16 ± 2.35, there were statistical differences ( P<0.05). Logistic regression analysis showed that irregular shape, unclear boundary, microcalcification, SMI blood flow signal grade, VI and ESR were independent risk factors for malignant breast mass ( P<0.05). ROC curve analysis results showed that the sensitivity, specificity and accuracy of SMI blood flow signal classification, VI and ESR combined in predicting breast tumor malignancy were 84.26%, 83.17% and 87.65%, respectively, and the area under the curve was 0.896, which were higher than the results predicted by each index alone. Conclusions:There are certain characteristic changes of SMI in benign and malignant breast masses. SMI combined with SR has good value in differential diagnosis of benign and malignant breast masses.