Objective: To investigate the distribution characteristics of ABO and Rh blood group antigen phenotypes among blood donors in the Yantai, Shandong. Methods: Blood samples from 310 180 voluntary blood donors in Yantai collected from January 2019 to December 2023 were tested for ABO and Rh blood group antigens using standard serological methods. RhD-negative samples were further typed for C, c, E, and e antigens. Population genetic analysis of blood groups was performed: allele frequencies were inferred from ABO phenotypes, and Rh allele/haplotype frequencies were estimated based on the proportion of RhD-negative donors and CcEe antigen typing, followed by Hardy-Weinberg equilibrium testing. Results: The phenotypic distribution frequency of ABO blood groups was B(32.72%)>O(28.93%)>A(27.65%)>AB(10.70%). The inferred allele frequencies were r(53.74%)>q(24.78%)>p(21.48%), consistent with Hardy-Weinberg equilibrium (P>0.05). A total of 1 872 Rh-negative donors (0.603%) were identified. The most common Rh phenotypes were ccdee (59.56%) and Ccdee (30.18%). The distribution of Rh antigen phenotypes deviated significantly from Hardy-Weinberg equilibrium (χ =37.15, P<0.001), with the cde haplotype showing the highest frequency. There was no statistically significant difference in ABO blood group distribution between RhD-positive and RhD-negative donors (P>0.05). Conclusion: The ABO blood group distribution among voluntary blood donors in Yantai is generally stable and consistent with population genetic equilibrium, whereas the Rh antigen phenotype distribution deviates from equilibrium, indicating potential underlying genetic structural differences.

Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective We investigated the effects of Xueguan Ruanhua Pills(XGRHW) on ferroptosis in ApoE-/- atherosclerotic mice through the nuclear factor E2 related factor 2 (Nrf2)/xCT/glutathione peroxidase 4 (GPX4) signaling pathway.Methods Ten male C57BL/6J mice in the normal group were fed normal chow. Additionally, 50 ApoE-/- mice were fed high-fat chow for 12 weeks, and were divided into the following five groups (10 mice per group): the model group, the XGRHW low-dose (2.34g/kg) group, the XGRHW high-dose (4.68 g/kg) group, the XGRHW high-dose combined with the Nrf2 inhibitor ML385 (0.03 g/kg) group, and the ferrostatin-1 (1 mg/kg) group. Drugs were administered for 6 weeks. The blood levels of four types of lipids were detected by an automatic lipid analyzer, lipid deposition in the aorta was observed by Oil Red O staining, histomorphological changes in the aortic sinus were observed by HE staining, the serum levels of Fe2+, MDA, GSH, and SOD were determined by colorimetric assays, and the expression levels of FTH1 and FTL in the aortic sinus were observed by immunofluorescence. The protein levels of Nrf2, xCT, and GPX4 in mouse aortic tissues were detected by Western blotting. The ultrastructural changes of aortic mitochondria were observed by transmission electron microscopy.Results Compared with the normal group, mice in the model group showed obvious lipid plaque deposition in the aorta, severely calcified lesions in the aortic sinus, elevated serum levels of TC, TG, LDL-C, Fe2+, and MDA, decreased levels of HDL-C, SOD, and GSH (P<0.01), and decreased protein expressions of aortic Nrf2, xCT, and GPX4 as well as the iron storage proteins FTH1 and FTL (P<0.01), and serve damage to mitochondrial structure and morphology. Compared with the model group, the relative aortic plaque area was decreased, calcified lesions in the aortic sinus were decreased, serum levels of TC, TG, LDL-C, Fe2+, and MDA were decreased, and HDL-C, SOD, and GSH levels were increased in the XGRHW low-dose and high-dose and ferrostatin-1 groups (P<0.05 or P<0.01), and Nrf2, xCT, GPX4, and the iron storage proteins FTH1 and FTL were upregulated in aortic tissues (P<0.05 or P<0.01), and mitochondrial structure approaching normal. In the XGRHW high-dose+ML385 group, compared with the XGRHW high-dose group, the levels of blood lipids and lipid peroxidation were increased and the protein levels of Nrf2, xCT, and GPX4 in aortic tissue and the iron storage proteins FTH1 and FTL were decreased (P<0.01), and mitochondrial structure was damaged indicating that ML385 could inhibit the therapeutic effect of the XGRHW in atherosclerotic mice.Conclusion The XGRHW can improve blood lipid levels and reduce the degree of arterial plaque lesions in atherosclerotic mice, and its mechanism of action may be related to activation of the Nrf2/xCT/GPX4 pathway to inhibit ferroptosis.

ObjectiveTo observe the effects of Tongmai Kaiqiao pills on the hypoxia-inducible factor-1α （HIF-1α）/adenovirus E1B 19 kD-interacting protein 3 （BNIP3） signaling pathway and mitochondrial autophagy in the hippocampus of the rat model of vascular dementia （VD）. MethodNinety male SD rats underwent adaptive feeding for one week before the study. Ten rats were randomly assigned to the sham group， where the common carotid artery was isolated without ligation. The remaining rats were subjected to sequential ligation of the common carotid artery for the modeling of VD. The successfully modeled rats were randomly assigned into the following groups： model， high-， medium-， and low-dose （27.6， 13.8， 6.9 g·kg^-1， respectively） Tongmai Kaiqiao pills， donepezil hydrochloride （0.45 mg·kg^-1）， and combination （27.6 g·kg^-1 Tongmai Kaiqiao pills + 2.5 mg·kg^-1 HIF-1α inhibitor YC-1） groups. After 4 weeks of treatment， samples were collected. Nissl staining and hematoxylin-eosin staining were performed to observe the loss of neurons and pathological changes， respectively， in the hippocampal region. Western blot was employed to determine the protein levels of HIF-1α， BNIP3， Beclin-1， and microtubule-associated protein 1 light chain 3B （LC3B） in the hippocampal tissue. Transmission electron microscopy was used to observe the mitochondrial ultrastructure and the number of autophagosomes in the hippocampal tissue. Immunofluorescence was employed to observe the fluorescence intensity of HIF-1α， BNIP3， and LC3B in the hippocampal tissue. ResultCompared with the sham group， the model group showed prolonged escape latency （P<0.01）， decreased number of platform crossings （P<0.01）， reduced and disarranged neuronal layers in the hippocampal region， decreased number of Nissl bodies， disrupted mitochondrial cristae， damaged mitochondrial double-membrane structures， increased number of autophagosomes， upregulated expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.05， P<0.01）， and enhanced fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with the model group， Tongmai Kaiqiao pills and donepezil hydrochloride shortened the searching time for the platform （P<0.01） and increased the number of platform crossings （P<0.01）. Moreover， the drugs increased the number of neurons with normal morphology and orderly arrangement and the number of Nissl bodies， alleviated the damage， increased the number of autophagosomes， upregulated the expression of HIF-1α， BNIP3， Beclin1， and LC3B （P<0.05， P<0.01）， and enhanced the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.05， P<0.01）. Compared with high-dose Tongmai Kaiqiao pills， the combination group prolonged the escape latency （P<0.01）， reduced the number of crossing platforms （P<0.01）， decreased the number of hippocampal neurons， aggravated the damage， decreased the number of Nissl bodies and autophagosomes， downregulated the expression of HIF-1α， BNIP3， beclin1， and LC3B （P<0.01）， and decreased the fluorescence intensity of HIF-1α， BNIP3， and LC3B （P<0.01）. ConclusionTongmai Kaiqiao pills may activate the HIF-1α/BNIP3 signaling pathway to promote the occurrence of mitochondrial autophagy， clear damaged mitochondria， provide energy for healthy cells， reduce neuronal cell death， and restore the brain function， thereby reducing ischemic damage to the hippocampal tissue， improving learning and memory abilities， and exerting therapeutic effects on VD in rats.

Objective:To investigate the reorganization patterns of sensorimotor cortex (SMC) and their relationship with upper limb motor function recovery in chronic stroke with severe hemiplegia.Method:Functional magnetic resonance imaging(fMRI) data were collected from 34 chronic stroke patients with severe hemiplegia who performed the passive fist clutch task with the affected hand before and after four weeks of rehabilitation. Additionally,data were collected from 29 healthy controls(HCs) who executed the pas-sive fist clutch task with unilateral hand. Differences in activation of SMC and the lateralization index(LI) be-fore and after the rehabilitation intervention were compared in the stroke group,and the correlation analysis was conducted with the Fugl-Meyer Assessment of Upper Extremity (FMA-UE).Result:In the healthy control group,the passive handgrip task predominantly activated the contralateral SMC. In the stroke group,changes in contralateral SMC activation during the affected hand task were classified into three patterns:recruitment,focusing,and no activation. The recruitment pattern showed that the activation of contralateral SMC increased after the intervention compared with that before the intervention. The focusing pat-tern showed that the activation of contralateral SMC decreased after the intervention compared with that before the intervention. The no activation pattern showed that there was no activation of contralateral SMC before and after the intervention. The LI in the recruitment group was similar to the HCs after the intervention,and the LI in the focusing group deviated from the HCs and was significantly higher than that of the HCs after the intervention(P<0.01). The FMA-UE scores of the three activation pattern groups were significantly in-creased after the intervention(P<0.01),while there were no significant differences both in the absolute values and absolute change values of FMA-UE and FMA-UE scores before and after the intervention between the re-cruitment group and the focusing group. In addition,there was a significant negative correlation between the relative change of contralateral SMC activation and the relative change of FMA-UE scores in the focusing group(r=-0.662,P=0.014).Conclusion:Chronic stroke patients with severe hemiplegia exhibit different reorganization patterns in the SMC during upper limb motor function recovery,particularly phenomena of SMC recruitment and concentration activation. These findings suggest that motor function recovery in chronic stroke patients with severe hemiple-gia does not rely on a single cortical functional reorganization pattern.

Objective:To investigate the changes in functional connectivity in transcallosal cortex connecting to the corpus callosum and its relationship with upper limb motor recovery in chronic stroke patients with severe hemiplegia.Method:The resting-state functional magnetic resonance imaging(fMRI) data were collected from 25 chronic stroke with severe hemiplegia before and after one-month rehabilitation intervention,as well as from 32 healthycontrols(HCs). The anatomical automatic labeling(ALL) atlas was used to identify 32 pairs of homotopic cortex regions directly connected via the corpus callosum for regions of interest(ROI)-level functional connectivity analy-sis. Differences in functional connectivity within the affected hemisphere,unaffected hemispheres,and between hemispheres were compared within and between groups. Furthermore,the correlation between functional connec-tivity and upper limb motor function scores(Fugl-Meyer assessment of upper extremity,FMA-UE)was analyzed.Result:Compared with HCs,the whole intrahemispheric functional connectivity in the stroke groups had no sig-nificant differences before and after rehabilitation intervention,while the whole interhemispheric functional con-nectivity was significantly reduced(P<0.01,FDR correction). Especially,the functional connectivity of homotopic regions decreased more significantly than that of interhemispheric non-homotopic regions,which involved the pre-frontal,sensorimotor,parietal,temporal,and occipital lobes. For the stroke groups,functional connectivity between the ipsilesional medial orbital gyrus and contralesional medial frontal gyrus was significantly enhanced after the intervention,compared with that before the intervention(P<0.01,FDR correction). The correlation analysis showed that the whole interhemispheric functional connectivity before the intervention was significantly positively correlated with FMA-UE scores(r=0.590,P=0.004). Five interhemispheric functional connectivities were significant-ly positively correlated with FMA-UE scores before the intervention in the stroke group(P<0.05),including three interhemispheric functional connectivities between homologous regions(involving the opercular part of the inferior frontal gyrus,ventral premotor area and primary motor cortex),and the other two interhemispheric functional con-nectivities between non-homologous regions(involving one connectivity between the ipsilesional lateral orbital gy-rus and the contralesional orbital part of the inferior frontal gyrus,and another connectivity between the ipsile-sional inferior parietal lobule and the contralesional superamarginal gyrus). Additionally,three interhemispheric functional connectivities between non-homologous regions in the pre-intervention stroke group were significantly positively correlated with the change of FMA-UE scores(P<0.05),involving the primary motor cortex,primary sensory cortex,ventral premotor area and superior temporal gyrus. Compared post-with pre-intervention,there was no significant correlation between changes in functional connectivity and FMA-UE scores.Conclusion:The weakened interhemispheric functional connectivity in transcallosal cortical regions may be an important factor contributing to the persistent motor dysfunction in chronic stroke patients with severe hemiple-gia. The interhemispheric functional connectivities within the sensorimotor cortex and between the ipsilesional sensorimotor cortex and the contralesional superior temporal lobe are closely related to motor recovery,possi-bly may be used to predict motor recovery of the upper limb in chronic stroke patients with severe hemiplegia.

Objective:To investigate the reorganization patterns of sensorimotor cortex (SMC) and their relationship with upper limb motor function recovery in chronic stroke with severe hemiplegia.Method:Functional magnetic resonance imaging(fMRI) data were collected from 34 chronic stroke patients with severe hemiplegia who performed the passive fist clutch task with the affected hand before and after four weeks of rehabilitation. Additionally,data were collected from 29 healthy controls(HCs) who executed the pas-sive fist clutch task with unilateral hand. Differences in activation of SMC and the lateralization index(LI) be-fore and after the rehabilitation intervention were compared in the stroke group,and the correlation analysis was conducted with the Fugl-Meyer Assessment of Upper Extremity (FMA-UE).Result:In the healthy control group,the passive handgrip task predominantly activated the contralateral SMC. In the stroke group,changes in contralateral SMC activation during the affected hand task were classified into three patterns:recruitment,focusing,and no activation. The recruitment pattern showed that the activation of contralateral SMC increased after the intervention compared with that before the intervention. The focusing pat-tern showed that the activation of contralateral SMC decreased after the intervention compared with that before the intervention. The no activation pattern showed that there was no activation of contralateral SMC before and after the intervention. The LI in the recruitment group was similar to the HCs after the intervention,and the LI in the focusing group deviated from the HCs and was significantly higher than that of the HCs after the intervention(P<0.01). The FMA-UE scores of the three activation pattern groups were significantly in-creased after the intervention(P<0.01),while there were no significant differences both in the absolute values and absolute change values of FMA-UE and FMA-UE scores before and after the intervention between the re-cruitment group and the focusing group. In addition,there was a significant negative correlation between the relative change of contralateral SMC activation and the relative change of FMA-UE scores in the focusing group(r=-0.662,P=0.014).Conclusion:Chronic stroke patients with severe hemiplegia exhibit different reorganization patterns in the SMC during upper limb motor function recovery,particularly phenomena of SMC recruitment and concentration activation. These findings suggest that motor function recovery in chronic stroke patients with severe hemiple-gia does not rely on a single cortical functional reorganization pattern.

Objective:To investigate the changes in functional connectivity in transcallosal cortex connecting to the corpus callosum and its relationship with upper limb motor recovery in chronic stroke patients with severe hemiplegia.Method:The resting-state functional magnetic resonance imaging(fMRI) data were collected from 25 chronic stroke with severe hemiplegia before and after one-month rehabilitation intervention,as well as from 32 healthycontrols(HCs). The anatomical automatic labeling(ALL) atlas was used to identify 32 pairs of homotopic cortex regions directly connected via the corpus callosum for regions of interest(ROI)-level functional connectivity analy-sis. Differences in functional connectivity within the affected hemisphere,unaffected hemispheres,and between hemispheres were compared within and between groups. Furthermore,the correlation between functional connec-tivity and upper limb motor function scores(Fugl-Meyer assessment of upper extremity,FMA-UE)was analyzed.Result:Compared with HCs,the whole intrahemispheric functional connectivity in the stroke groups had no sig-nificant differences before and after rehabilitation intervention,while the whole interhemispheric functional con-nectivity was significantly reduced(P<0.01,FDR correction). Especially,the functional connectivity of homotopic regions decreased more significantly than that of interhemispheric non-homotopic regions,which involved the pre-frontal,sensorimotor,parietal,temporal,and occipital lobes. For the stroke groups,functional connectivity between the ipsilesional medial orbital gyrus and contralesional medial frontal gyrus was significantly enhanced after the intervention,compared with that before the intervention(P<0.01,FDR correction). The correlation analysis showed that the whole interhemispheric functional connectivity before the intervention was significantly positively correlated with FMA-UE scores(r=0.590,P=0.004). Five interhemispheric functional connectivities were significant-ly positively correlated with FMA-UE scores before the intervention in the stroke group(P<0.05),including three interhemispheric functional connectivities between homologous regions(involving the opercular part of the inferior frontal gyrus,ventral premotor area and primary motor cortex),and the other two interhemispheric functional con-nectivities between non-homologous regions(involving one connectivity between the ipsilesional lateral orbital gy-rus and the contralesional orbital part of the inferior frontal gyrus,and another connectivity between the ipsile-sional inferior parietal lobule and the contralesional superamarginal gyrus). Additionally,three interhemispheric functional connectivities between non-homologous regions in the pre-intervention stroke group were significantly positively correlated with the change of FMA-UE scores(P<0.05),involving the primary motor cortex,primary sensory cortex,ventral premotor area and superior temporal gyrus. Compared post-with pre-intervention,there was no significant correlation between changes in functional connectivity and FMA-UE scores.Conclusion:The weakened interhemispheric functional connectivity in transcallosal cortical regions may be an important factor contributing to the persistent motor dysfunction in chronic stroke patients with severe hemiple-gia. The interhemispheric functional connectivities within the sensorimotor cortex and between the ipsilesional sensorimotor cortex and the contralesional superior temporal lobe are closely related to motor recovery,possi-bly may be used to predict motor recovery of the upper limb in chronic stroke patients with severe hemiplegia.

The injury of vascular endothelial cells is not only the initial condition to promote the occurrence of early atherosclerosis （AS） plaques， but also an important link in the pathogenesis of AS. The microRNA （miRNA）， as an important medium of intercellular communication and gene regulatory factor， can affect vascular endothelial function and participate in the development of AS. The molecular mechanism of miRNA’s multi-target intervention in vascular endothelial cell injury has become a hot topic in the research of cardiovascular diseases. Monomers of traditional Chinese medicines such as ginsenoside Rb2 and paeonol， as well as traditional Chinese medicine for resolving phlegm and removing blood stasis could regulate miRNA to improve endothelial cell inflammation； astragaloside Ⅳ， dihydromyricetin and notoginsenoside could target miRNA and inhibit vascular endothelial oxidative stress； Danhong injection， Jianpi qutan and huayu prescription and paeonol could affect endothelial autophagy through miRNA； resveratrol， Bushen huoxue formula and Bushen tongmai formula could inhibit vascular endothelial aging by miRNA； dendrobine played an active role in regulating miRNA and improving endoplasmic reticulum stress. In the future， more in- depth research is needed on the effectiveness， mechanism of action， diagnosis and treatment plans， and safety of targeted regulation of miRNA for AS therapy by traditional Chinese medicine.

Hepatitis B virus (HBV) infection is closely associated with the adverse events such as liver cirrhosis, liver cancer, and liver failure and remains a serious threat to human health. Pegylated interferon is an indispensable drug for the treatment of chronic hepatitis B (CHB), and interferon-stimulated genes are associated with a variety of viruses, but few studies have mentioned their association with hepatitis B and their predictive effect after the treatment of hepatitis B with interferon. This article introduces the predictive factors for interferon treatment of CHB and summarizes the association of interferon-stimulated genes with hepatitis B and their predictive effect, so as to provide a reference for clinical work and basic research.