Cerebral small vessel disease is a common cerebrovascular disease in clinical practice.It is mainly characterized by insidious onset and slow development.Some may have acute attack.The imaging features of cerebral small vessel disease mainly include cerebral white matter lesions,lacunar infarction,cerebral microbleed and cerebral perivascular space expansion.It is closely associated with cognitive impairment.All imaging findings can occur simultaneously and interact,further aggravate cognitive impairment,and ultimately lead to dementia.Therefore,the influence of cerebral small vessel disease on the quality of life and social function of the patients cannot be ignored.

Objective To study on the effect of DNA vaccine, p(Aβ3-10) 10-mIL-4, immunization on behavior and brain Aβ deposition in APP/PS1 transgenic mice.Methods DNA vaccine p(Aβ3-10) 10-mIL-4 was constructed which expressed fusion protein of ten tandem repeats of Aβ3-10 and mouse IL-4.APP/PS1 transgenic mice were vaccinated with p (Aβ3-10) 10-mIL-4.Aβ42 peptide and pcDNA3.1 (+) were injected to the control groups.Anti-Aβ antibody titers were detected before and after vaccination by enzyme-linked immunosorbent assay (ELISA) ,the spatial learning and memory ability of the mice were evaluated by Morris water maze.The senile plaques in mouse brains were detected by immunohistochemistry.Results Compare with pcDNA3.1 (+) group,immunization with the vaccine p (Aβ3-10) 10-mIL-4 in APP/PS1 mice induced high-titer Anti-Aβ antibodies ((27.49±4.51) μg/ml, P＜0.01) ,decreased Aβ deposition (reduced senile plaque number in the cortex and hippocampus by 52.86％ and 58.29％ respectively, P＜0.01) and improved their cognitive ability.Conclusions The immunization with p(Aβ3-10)10-mIL-4 in APP/PS1 mice achieve an ideal effect of vaccination, and p(Aβ3-10) 10-mIL-4 can be an alternative Alzheimer's disease vaccine to further study.

Post-stroke cognitive impairment (PSCI) refers to the decline of cognitive function after stroke, including mild cognitive impairment and dementia. It is very important to prevent PSCI, and it is a direction worth exploring to find the predictors. This article reviews the research progress of the predictors of PSCI, including demographic characteristics, imaging characteristics of stroke onset, stroke itself characteristics, and molecular markers, hoping to help screen high-risk patients and intervene in time to delay the occurrence and development of PSCI.

BACKGROUND:For pediatric patients with aplastic anemia in China, it is difficult to find human leucocyte antigen-matched sibling donors that are mostly replaced by parental donors.
OBJECTIVE:To retrospectively analyze the clinical efficacy and safety of parental haploidentical peripheral blood hematopoietic stem cel transplantation in children with relapsed and refractory severe aplastic anemia.
METHODS:Seventeen children with relapsed and refractory severe aplastic anemia who had no matched sibling or unrelated donor and failed to respond to immunosuppressive therapy were subjected to parental haploidentical peripheral blood hematopoietic stem cel transplantation. A conditioning regimen of fludarabine+cyclophosphamide+rabbit anti-human thymocyte immunoglobulin antibody and the triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease.
RESULTS AND CONCLUSION: (1) Of the 17 children, 16 cases (94%) reached hematopoietic reconstitution, and the median time of neutrophils≥ 0.5×109/L and platelets≥ 20×109/L was 13 (11-15) days and 17 (12-28) days, respectively. (2) Incidence of acute graft-versus-host disease was 47% (8 of 17 cases), including 29% (5/17) of grades I-II and 18% (3/17) of grades III-IV. Incidence of chronic graft-versus-host disease was 41% (7/17). (3) With a median folow-up duration of 268 (43-753) days, the overal survival rate was 70.6% (12/17). Five dead cases (29%) belonged to transplantation-related death, including one case of fungal skin infections, one case of graft-versus-host disease, three cases of severe lung infection. No relapse case was reported. These findings indicate that if there are no matched sibling or unrelated donors and the immunosuppression effect is poor, parental haploidentical peripheral blood hematopoietic stem cel transplantation is a safe and effective salvage treatment for children with relapsed and refractory severe aplastic anemia.

Aim To investigate the effect of oxymatrine on lipid metabolism regulated genes in liver in fat-in-duced insulin resistance in ApoE -/- mice.Methods Seventeen C57BL/6J male mice were selected in normal control group.Sixty-eight ApoE -/- mice with high fat diet for 1 6 weeks,were randomly divided into model group,oxymatrine low,middle and high dose groups.Then they were gavaged for 8 weeks.Body weight and general biochemical indicators were deter-mined in mice.The mRNA and protein expression lev-els of LPL,FAT/CD36,CPT1 ,UCP2,SREBP-1 c,FAS and ACC were examined by real-time PCR and West-ern blot in the liver.Results Compared with model group,oxymatrine reduced body weight(BW),fasting
blood glucose (FBG),cholesterol (TC ),triglyceride (TG),free fatty acids(FFA),fasting plasma insulin (FINS)and insulin resistance index(HOMA-IR)(P <0.05),while improved glucose infusion rate (GIR). Oxymatrine down-regulated the mRNA and protein ex-pression of LPL,FAT/CD36,UCP2,SREBP-1 c,FAS and ACC(P <0.05),and up-regulated the mRNA and protein expression of CPT1 in varying degrees (P <0.05).Conclusion Oxymatrine can regulate the ex-pression of lipid metabolism regulated genes in liver and improve insulin resistance in ApoE -/- mice in-duced by high fat diet.

Cerebral microbleeds (CMBs) are a imaging manifestation of small vessel disease, and have a marked impact on the recurrence and on hemorrhagic transformation of ischemic stroke. Atrial fibrillation (AF) is a common arrhythmia,w hich significantly increases the risk of stroke,and the incidence of CMB in AF patients is also significantly higher than that in non-AF patients.Antithrombotic therapy is the cornerstone of stroke prevention,but it also increases the risk of bleeding.The benefit of stroke prevention and the bleeding risk should be assessed in AF patients w ith CMBs.

Objective To investigate the correlation between 24 h ambulatory blood pressure monitoring (ABPM) parameters and white matter hyperintensities (WMHs).Methods A cross-sectional analysis was performed in patients who visited the Department of Neurology,Liaoning People's Hospital,and showed WMHs on the head MRI and completed 24 h ABPM in the same period of hospitalization from September 2016 to October 2018.Periventricular white matter hyperintensities (PVWMHs) and deep white matter hyperintensities (DWMHs) were evaluated using the modified Scheltens scale respectively,and the sum of the two was used as the overall severity score of WMHs.The enrolled patients were grouped according to the tertiles of the overall WMH score.Multivariate ordinal logistic regression analysis was used to investigate independent risk factors affecting overall WMH scores.Multivariate linear regression analysis was used to investigate the influencing factors of PVWMH and DWMH scores.Results A total of 201 patients were enrolled,aged (62.7 ± 10.3) years (range 45-88 years),82 males (40.8％),and 123 patients (61.2％) with hypertension.The total WMH scores were 1-27.According to the tertiles,64 patients (31.8％) were divided into lower tertile group (1-3),65 (32.3％) in the middle tertile group (4-8),and 72 (35.8％) in the higher tertile group (9-27).There was significant difference in age between any two WMH score groups,namely,the high tertile group ＞ middle tertile group ＞ low tertile group (69.5 ± 8.5 years vs.63.1 ±9.2 years vs.54.5 ±6.9 years;all P＜0.001).The proportion of hypertension in the middle tertile group (66.2％) and the higher tertile group (69.4％) were significantly higher than those in the lower tertile group (46.9％;all P＜0.05).The homocysteine in the higher tertile group was significantly higher than that in the lower tertile group (15.6 [12.7-19.7]μmol/Lvs.14.1[12.5-15.9]μmol/L;P ＜0.05).In terms of 24 h ABPM parameters,the 24 h mean systolic blood pressure (24 h SBP) in the higher tertile group was higher than that in the lower tertile group,and the nighttime mean systolic blood pressure (nSBP) level in the higher tertile group was higher than that in the lower and middle tertile groups,the SD of daytime systolic blood pressure (dSBPSD) and the SD of the nighttime systolic blood pressure (nSBPSD) in the higher tertile group were higher than those in the lower tertile group,and dSBPSD of the middle tertile group was higher than of the lower tertile group.The above differences were statistically significant (all P ＜0.05).Multivariate ordinal logistic regression analysis showed that the increased age (odds ratio[OR] 1.143,95％ confidence interval[CI] 1.104-1.185;P＜0.001),24 h SBP (OR 1.026,95％ CI 1.005-1.048;P =0.015),dSBP (OR 1.022,95％ CI 1.001-1.043;P =0.036),nSBP (OR 1.026,95％ CI 1.006-1.046;P=0.011),dSBPSD (OR 1.119,95％ CI 1.023-1.221;P=0.013),and nSBPSD (OR 1.107,95％ CI 1.022-1.200;P=0.013) were independently positively correlated with the overall WMH score.Multivariate linear regression showed that age (β=0.607,95％ CI 0.500-0.714;P＜0.001),24 h SBP (β=0.182,95％ CI 0.075-0.289;P=0.001),dSBP (β=0.156,95％ CI 0.049-0.264;P=0.004),and nSBP (β =0.200,95％ CI 0.092-0.307;P ＜0.001) were independently positively correlated with the PVWMH score;age (β =0.505,95％ CI 0.387-0.622;P ＜0.001),24 h SBP (β =0.132,95％ CI 0.015-0.248;P =0.027),dSBP (β =0.127,95％ CI0.011-0.243;P =0.032),nSBP (β =0.148,95％ CI 0.031-0.265;P =0.013),and nSBPSD (β =0.133,95％ CI 0.016-0.250;P=0.027) were independently positively correhted with the DWMH score.Conclusion The increased age,ambulatory systolic blood pressure level (24 h,daytime,nighttime) and systolic blood pressure variability level (dSBPSD and nSBPSD) were independently associated with the severity of WMHs.

Imaging findings of cerebral small vessel diseases (CSVD) include white matter lesions,enlarged perivascular spaces,lacunar infarcts and cerebral microbleeds.These imaging markers often appear at the same time.In recent years,the "total small vessel diseases score" was proposed by combining the different magnetic resonance imaging (MRI) markers into one measure of CSVD,so that we can capture all the brain damage from CSVD more accurately through the evaluation of total MRI burden.This paper reviews the research progress of total small vessel diseases score and its application.

Objective:To explore the correlation between abdominal aortic calcification and serum cell division cycle 42 (CDC-42) in maintenance hemodialysis (MHD) patients, and to explore the influencing factors of them.Methods:A cross-sectional study was conducted in the Blood Purification Center of Qingdao Municipal Hospital,112 patients who underwent MHD for more than 6 months from October 2019 to March 2021 were selected. The abdominal aortic calcification score (ACCs) was calculated by reference to the abdominal lateral X flat tablets. According to AACS, 50 cases were divided into no and mild calcification group (0≤AACS<5 points) and 62 cases were divided into moderate and severe calcification group (AACS≥5 points). The level of serum CDC-42 was detected by enzyme linked immunosorbent assay (ELISA). Taking the median serum CDC-42 level as the boundary, 56 cases were divided into low CDC-42 group and high CDC-42 group. Spearman correlation analysis was used to analyze the correlation between indicators. The risk factors of elevated CDC-42 and abdominal aortic calcification in MHD patients were explored by multivariate logistic regression analysis, and the variables were included by entry method.Results:In 112 patients, 91 cases (81.25%, 91/112) had abdominal aortic calcification, and the median serum CDC-42 level was 466.56 (335.56,623.57) ng/L. CDC-42, AACs, age, dialysis age, diabetic nephropathy, glycosylated hemoglobin, alkaline phosphatase, parathormone and calcium in the no and mild calcification groups were 347.77 (291.20, 419.53) ng/L, 1.00 (0.00, 3.00) points, (57.18±6.25) years, 31.50 (15.00, 49.25) months, 34.00%(17/50), (6.63±0.97)%, 116.22 (87.32, 152.13) U/L, 258.57 (143.40, 433.31) ng/L, (2.18±0.26) mmol/L, and in the moderate to severe calcification group were 602.69 (489.61, 762.73) ng/L, 10.00 (7.00, 16.25) points, (60.81±7.12) years, 49.00 (18.00, 67.00) months, 53.23%(33/62), (7.07±1.20)%, 144.34 (99.71, 201.76) U/L, 336.57 (230.63, 506.00) ng/L,(2.28±0.26) mmol/L, with statistically significant differences between the two groups(The statistical values were 6.99, 9.11, 2.83, 2.45, 4.14, 2.08, 2.04, 2.16 and 1.99, respectively, all P<0.05). CDC-42, AACs, glycosylated hemoglobin and parathormone in the low CDC-42 group were 336.50 (295.10, 395.25) ng/L, 2.00 (0.00, 4.00) points, (6.62±1.06) %, 250.60 (140.20, 462.02) ng/L,and in the high CDC-42 group were 622.92 (558.11, 836.65) ng/L, 10.00 (6.25, 15.75) points, (7.13±1.13) %, 347.21 (240.40,501.20) ng/L, with statistically significant differences between the two groups (The statistical values are 6.51, 5.21, 2.43 and 2.54, respectively,all P<0.05). Abdominal aortic calcification has positive correlations with CDC-42 ( r s=0.704, P<0.001), age ( r s=0.308, P=0.001), dialysis years ( r s=0.198, P=0.036), glycosylated hemoglobin ( r s=0.358, P<0.001), alkaline phosphatase ( r s=0.187, P=0.048), parathormone ( r s=0.437, P<0.001), serum calciu m( r s=0.323, P=0.001) and serum phospho-rus ( r s=0.251, P=0.007), and negative correlation with serum albumin( r s=-0.276, P=0.003). This study has confirmed that high serum CDC-42 ( OR=1.010, 95%CI:1.004-1.016, P=0.001) and senior dialysis age ( OR=1.033, 95%CI:1.006-1.061, P=0.018) were independent risk factors for moderate to severe abdominal aortic calcification.Serum CDC-42 levels has positive correlation with AACs ( r s=0.704, P<0.001), age ( r s=0.240, P=0.011), dialysis age ( r s=0.191, P=0.044), glycosylated hemoglobin ( r s=0.350, P<0.001), parathormone ( r s=0.380, P<0.001) and serum calcium ( r s=0.235, P=0.013). This study learned that,high AACs ( OR=1.185, 95%CI:1.037-1.354, P=0.013) and high parathormone ( OR=1.005, 95%CI:1.001-1.009, P=0.009) were independent risk factors for high CDC-42. The area under the receiver operating characteristic curve (ROC-AUC) of serum CDC-42 in predicting moderate and severe abdominal aortic calcification in MHD patients was 0.885. When the cut-off point was 466.56 ng/L, the predictive sensitivity and specificity were 79% and 86% respectively. Conclusion:The degree of abdominal aortic calcification in MHD patients was positively correlated with the level of serum CDC-42. High serum CDC-42 and high dialysis age were independent risk factors for abdominal aortic calcification in MHD patients. High AACS and high parathyroid hormone were independent risk factors for the increase of serum CDC-42 in MHD patients .

OBJECTIVE Taking Professor Zhou Zhongying's clinical cases of treating hyperthyroidism as the research object,this article explored the use of the TabNet model based on neural networks to discover the diagnosis and treatment rules of hyperthyroid-ism,providing a method reference for inheriting the academic thoughts of famous veteran traditional Chinese medicine practitioners and assisting clinical diagnosis and treatment.METHODS Based on the clinical diagnosis and treatment cases of hyperthyroidism of Pro-fessor Zhou Zhongying and his team,standardized and structured training data were constructed;algorithms based on attention mecha-nism and sparse feature selection mechanism were studied;a pathogenesis prediction model was constructed by inputting standardized clinical manifestations,standardized tongue and pulse conditions;core symptoms,pathogenesis and medication were analyzed,as well as the relationship between the three.RESULTS The trained prediction model was used to predict the 6 pathogenesis of liver stagna-tion,liver fire,phlegm fluid,kidney deficiency,yin deficiency,and blood stasis.Compared with multi-label classification models constructed by classic algorithms such as decision trees and random forests,this model had better classification and prediction indica-tors.Mining was carried out through the decision tree algorithm,and 6 core pathogenesis corresponding Chinese medicine groups were summarized:vinegar-baked Bupleurum chinense,prunella vulgaris,oyster,processed Carapax trionycis,Scrophularia ningpoensis,Asparagus cochinchinensis,Ophiopogon japonicus,etc.CONCLUSION Using the TabNet algorithm on clinical medical record data to build a pathogenesis prediction model based on clinical manifestations,tongue and pulse conditions can effectively predict the core pathogenesis,and then discover the connection between symptoms,pathogenesis and medication,providing methodological references for the inheritance of academic ideas of famous veteran traditional Chinese medicine practitioners and clinical auxiliary diagnosis and treatment decision-making.